Research Update:American Ginseng or Panax quinquefolius.

  seminal trace...American Ginseng Extract.Panax quinquefolius.Panax quinquefolium extract.Ginsenosides 20%80%,CAS.NO:090045-38-8.North American ginseng extract.5:1.10:1.20:1.etc.Ginseng, Panax quinquefolium, ext....

 


   Phytochemical info of American Ginseng or Panax quinquefolius

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 Definition:American Ginseng or Panax quinquefolius are majorly composed of
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   Research Update:American Ginseng or Panax quinquefolius.

  Protective Effect of Heat-Processed American Ginseng against Diabetic Renal Damage in Rats.:J Agric Food Chem. 2007 Oct 17;55(21):8491-7. Epub 2007 Sep 26.

 We investigated the effects of American ginseng (AG) and heat-processed American ginseng (H-AG) on diabetic renal damage using streptozotocin (STZ)-induced diabetic rats in this study. The diabetic rats showed a loss of body weight gain, and increases in kidney weight, food intake, water intake, and urine volume, whereas the oral administration of H-AG at a dose of 100 mg/kg of body weight per day for 20 days attenuated these diabetes-induced physiological abnormalities. Among the renal function parameters, the elevated urinary protein levels in diabetic control rats were significantly decreased by the AG or H-AG administrations, and the decreased creatinine clearance level was significantly increased in H-AG-administered rats. In addition, the markedly high serum levels of glucose and glycosylated protein in diabetic control rats were significantly decreased by the administration of H-AG, implying that H-AG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and glycosylation of serum proteins. Although no significant ameliorations were shown in overexpressed protein expressions related to diabetic oxidative stress by the AG or H-AG administrations, the accumulation of N (epsilon)-(carboxymethyl)lysine and receptors for advanced glycation endproduct (AGE) expressions were significantly reduced by the administration of H-AG. On the basis of these results, we found that AG and H-AG inhibit AGE accumulation in diabetic rat kidney by their hypoglycemic and renal function ameliorating effects, and this effect was stronger in the H-AG-administered group than in the AG-administered group. These findings indicate that H-AG may have beneficial effect on pathological conditions associated with diabetic nephropathy.

  Medicinal flowers. XVII. New dammarane-type triterpene glycosides from flower buds of American ginseng, Panax quinquefolium L.:Chem Pharm Bull (Tokyo). 2007 Sep;55(9):1342-8.

 Five new dammarane-type triterpene glycosides, floralquinquenosides A, B, C, D, and E, were isolated from the flower buds of American ginseng, Panax quinquefolium L., together with 18 known dammarane-type triterpene glycosides and 3 flavonoid glycosides. The structures of new floralquinquenosides were elucidated on the basis of chemical and physicochemical evidence.

  Potential interactions between complementary/alternative products and conventional medicines in a medicare population.:Ann Pharmacother. 2007 Oct;41(10):1617-24. Epub 2007 Sep 4.Elmer GW, Lafferty WE, Tyree PT, Lind BK.Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.

 BACKGROUND: Despite the high prevalence of complementary and alternative medicine (CAM) product use among the elderly, little is known about the extent of concurrent CAM-conventional medicine use and the potential for adverse reactions. OBJECTIVE: To determine the prevalence of CAM product use concurrent with conventional medications, prescription and nonprescription, in a Medicare population and assess the risk for adverse interactions. METHODS: Retrospective analysis was performed on Cardiovascular Health Study interview data from 1994, 1995, 1997, and 1999. The prevalence of concurrent combinations of CAM products and conventional drugs was tabulated. The adverse interaction risks were categorized as unknown, theoretical, and significant. RESULTS: Of 5052 participants, the median age was 75, 60.2% were female, 16.6% were African American, and 83.4% were white. The percent using CAM products during the 4 time periods was 6.3%, 6.7%, 12.8%, and 15.1%. The percent using both CAM products and conventional drugs was 6.0%, 6.2%, 11.7%, and 14.4%. Of these, 294 (5.8%) individuals took combinations considered to have a significant risk for an adverse interaction. Combinations with risk were observed on 393 separate interviews. Most (379) involved a risk of bleeding due to use of ginkgo, garlic, or ginseng together with aspirin, warfarin, ticlopidine, or pentoxifylline. An additional 786 observations of combinations were considered to have some, albeit theoretical or uncertain, risk for an adverse interaction. CONCLUSIONS: Concurrent use of CAM products and conventional medicines in a Medicare population was found to be common. Research to define the risks of combining ginkgo and garlic supplements with aspirin should be of high priority.

  Quantification of Two Polyacetylenes in Radix Ginseng and Roots of Related Panax Species Using a Gas Chromatography-Mass Spectrometric Method.:J Agric Food Chem. 2007 Aug 28;Liu JH, Lee CS, Leung KM, Yan ZK, Shen BH, Zhao ZZ, Jiang ZH.School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, School of Pharmacy, Jilin University, Changchun, China, Jilin Academy of Traditional Chinese Medicine, Changchun, China, and Shanghai Shennong Pharmaceuticals Co. Ltd., Shanghai, China.

 A sensitive method for quantitating the pharmacologically active polyacetylenes panaxynol and panaxydol in Radix Ginseng was developed using a capillary gas chromatography-mass spectrometric (GC-MS) method. The detection mode of selected ion monitoring (SIM) allowed sensitive and selective quantitation of the two compounds in ginseng. Method validation showed that the GC-MS method has much lower detection and quantitation limits than the high-performance liquid chromatography (HPLC)-UV method. This indicates that GC-MS is particularly useful for the analysis of polyacetylene compounds, which have relatively low abundances compared with ginsenosides in ginseng. Based on the quantitative results of different types of ginseng herbs, it was found that the panaxydol and panaxynol contents were higher in forest ginseng than in cultivated ginseng. This method was further applied to the quantitative analyses of panaxynol and panaxydol in Radix Notoginseng and American ginseng. The ratio of panaxydol to panaxynol can be utilized as a marker for differentiating ginseng, notoginseng, and American ginseng. This study introduces the first GC-MS method for the quantitative analysis of polyacetylenes in herbs of the Panax genus. Keywords: Ginseng; Panax; GC-MS; polyacetylene; panaxydol; panaxynol.

  Commonly used antioxidant botanicals: active constituents and their potential role in cardiovascular illness.:Am J Chin Med. 2007;35(4):543-58.Wang CZ, Mehendale SR, Yuan CS.Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, The University of Chicago, Chicago, Illinois 60637, USA.

 Cardiovascular disease continues to be the leading cause of death in the US. Recent studies found that reactive oxygen species (ROS) have been incriminated in the pathogenesis of both acute and chronic heart diseas. Many botanicals possess antioxidant properties, and these herbal antioxidants may protect against cardiovascular diseases by contributing to the total antioxidant defense system of the human body. In this article, we reviewed the antioxidant components and properties of four putative antioxidant botanicals (i.e., grape seeds, green tea, Scutellaria baicalensis, and American ginseng), and their potential role in treating cardiovascular illness. The antioxidant activities of the herbal active constituents, and the relationship between their chemical structures and biological functions were also discussed. Further investigations are needed on the mechanisms of action of these botanicals as they affect salient cellular and molecular pathways involved in major diseases. Data obtained from future studies will have the potential for translation into practical benefits for human health.


  Protective effects of American ginseng (Panax quinquefolium) against mitomycin C induced micronuclei in mice.:Phytother Res. 2007 Jul 27;Pawar AA, Tripathi DN, Ramarao P, Jena G.Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Sector©\67, S.A.S. Nagar, Punjab 160062, India.

 Mitomycin C (MMC) is a highly active anticancer drug commonly used alone and in combination with other chemotherapeutic agents for the treatment of different cancers. Its bioactivated form critically damages the DNA present in both rapidly dividing cancerous cells as well as in normal cells. Genotoxicity in the normal cells makes this drug highly toxic; thereby decreasing its therapeutic index for clinical use. The study investigated the chemoprotective potential of American ginseng root extract against MMC by using the micronuclei test in a mouse test system. Pre-treatment with ginseng at doses 50 mg/kg and 100 mg/kg, p.o. for 3 and 7 days significantly decreased the frequency of micronucleated polychromatic erythrocytes (PCEs). Similar protective effects were also observed during co-treatment with ginseng at similar doses for 3 and 7 days. The present results indicate that American ginseng extract is capable of suppressing the chromosomal aberration induced by MMC in mice. Thus, American ginseng may be a potent chemoprotective agent against the toxicity of the anticancer drug, mitomycin C.

  Increase in the free radical scavenging activities of American ginseng by heat processing and its safety evaluation.:J Ethnopharmacol. 2007 Sep 5;113(2):225-32. Epub 2007 Jun 2.

 We previously reported the increase in free radical scavenging activities of Korean ginseng (KG, Panax ginseng C.A. Meyer) by heat processing. In the United States, American ginseng (AG, Panax quinquefolium L.) is a more commonly used herbal medicine than KG, but heat processing-induced chemical and activity changes of AG are not well known. Therefore, we compared the changes in ginsenosides, total phenolic contents, Maillard reaction product (MRP) levels, and several free radical scavenging activities of AG by heat processing. In addition, a short-term toxicity assessment in rats was also conducted for the identification of certain toxic effects of AG after heat processing. As a result, the ginsenosides were deglycosylated at carbon-20 and their total contents were lowered, but the total phenolic contents and MRP levels of AG were about 2.5 and 9.3 times increased, respectively, by heat processing. In addition, all free radical scavenging activities of AG were significantly increased by heat processing. Moreover, there were no toxic signs or decreases in renal and hepatic function parameters of rats administered heat-processed AG. Therefore, heat processing, as in KG, is a useful method to enhance the free radical scavenging activities of AG by the increases in total phenolic contents and MRP levels.

  Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots.:Planta Med. 2007 Jun;73(7):669-74. Epub 2007 May 31.Wang CZ, Aung HH, Ni M, Wu JA, Tong R, Wicks S, He TC, Yuan CS.Tang Center for Herbal Medicine Research, University of Chicago, Chicago, Illinois 60637, USA.

 Red Asian ginseng ( Panax ginseng C. A. Meyer, Araliaceae) is used in many Oriental countries. In this study, the saponin constituents and anticancer activities of steamed American ginseng ( Panax quinquefolius L.) roots were evaluated. The contents of 12 ginsenosides in the roots were determined using high performance liquid chromatography (HPLC). After the steaming treatment (100 - 120 degrees C for 1 h and 120 degrees C for 0.5 - 4 h), the quantity of 7 ginsenosides decreased and that of 5 others increased. The content of ginsenoside Rg3, a previously recognized anticancer compound, increased significantly when the root was steamed at 120 degrees C for 0.5 - 3 h. The antiproliferative effects of unsteamed and steamed (120 degrees C for 1 h and 2 h) American ginseng root extracts were assayed by the modified trichrome stain (MTS) method using three cancer cell lines (SW-480, HT-29, NSCLC). Heat-processing increased the antiproliferative effect of American ginseng significantly, and the activity of the extract from roots steamed for 2 h was greater than that of roots steamed for 1 h. Chemical constituents and antiproliferative activities of white and red Asian ginseng have also been evaluated. Five representative ginsenosides, Rb1, Rd, Re, Rg2 and Rg3, were studied. Ginsenoside Rg3 had the most potent effect. The antiproliferative activities of red American ginseng are augmented when ginsenoside Rg3 is increased.

  Effect of panax quinquefolius saponin on angiogenesis and expressions of VEGF and bFGF in myocardium of rats with acute myocardial infarction.:Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 Apr;27(4):331-4. Chinese.Wang CL, Shi DZ, Yin HJ.Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing. wcl207@yahoo.com.cn

 OBJECTIVE: To study the effect of Panax quinquefolius Saponin (PQS), an extraction from stem and leaf of American ginseng, on vascular regeneration in infarcted area, and expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in myocardium of rats with acute myocardial infarction (AMI). METHODS: Fifty male Wistar rats were established into AMI model successfully and randomly divided into 5 groups equally, i.e. the model group, the high, middle and low dose PQS groups and the metoprolol group. They were treated with saline, different doses of PQS (54 mg/kg x d, 27 mg/kg x d, 13.5 mg/kg x d)and metoprolol (4.5 mg/kg x d) respectively, by gavage once a day for 14 days. Besides, a sham operated group and a normal control group were set up for control with 10 rats in each group. All rats were killed on the 15th day. Six samples of heart were chosen from each group for examining expressions of VEGF, bFGF and the VIII coagulation factor under light microscopy by immunohistochemical staining, and the quantitative analysis on positive responsive intensity of VEGF and bFGF was conducted on the other 4 heart samples using the image analysing system, then mean micro-vessel density (MMVD) was calculated. RESULTS: The expressions of VEGF and MMVD were higher in the high and the middle dose PQS groups than those in the model group (P < 0.05) and the expression of bFGF was higher in the three PQS groups than that in the model group (P < 0.05). CONCLUSION: PQS can protect myocardium from ischemic injury in rats after AMI by way of promoting angiogenesis in the infarcted or ischemic area of myocardium and up-regulating expressions of VEGF and bFGF in myocardial cells.

  Complementary and alternative medicine use decreases adherence to HAART in HIV-positive women.:AIDS Care. 2007 May;19(5):589-93.Owen-Smith A, Diclemente R, Wingood G.Emory University, Behavioral Science and Health Education, Atlanta, GA, USA. aowensm@emory.edu

 The use of complementary and alternative medicine (CAM) to treat chronic illnesses, especially HIV, is becoming increasingly widespread. Given this popularity, it is critical to understand how HIV-positive individuals use CAM and, more specifically, whether CAM use impacts their adherence to prescribed antiretroviral regimens (HAART). The present study examined the relationship between CAM use and HAART adherence among HIV+ women. Data were analysed from 366 HIV-positive, mostly African-American women, aged 18-50 years in Alabama and Georgia who were enrolled in an intervention to reduce high-risk sexual behaviour. At enrollment data were collected describing use of CAM and HAART use. Women were classified as CAM users if they reported taking herbal/natural immunity boosters (Chinese herbs, mushrooms, garlic, ginseng or algae) or multivitamins, or reported using religious/psychic health or bodywork to treat HIV. Women were classified as non-adherent if they reported missing any doses of their HAART medication in the 30 days preceding baseline assessment. Logistic regressions models, adjusted for potential confounders, were used to investigate the relationship between CAM use and HAART adherence. Women using CAM (immunity boosters or vitamins), relative to non-CAM users, were 1.69 times more likely to report missing HAART doses in the last 30 days (CI: 1.02-2.80; P=.041) even after adjusting for age, education, race, religion and income. The findings provide preliminary evidence that patients using CAM may be doing so as an alternative to traditional medicine as opposed to complementing prescribed HARRT treatment regimens. The inconsistent use of HAART is problematic given its association with drug resistance. Therefore, health care providers and patients should have explicit dialogues about how to effectively integrate CAM practices into traditional treatment regimens so that the safety and health of HIV-positive patients is not compromised.


  Ineffectiveness of American ginseng in the prevention of dimethylbenzanthracene-induced mammary tumors in mice.:Oncol Res. 2006;16(6):251-60.Wurz GT, Marchisano-Karpman C, DeGregorio MW.Department of Internal Medicine, Division of Hematology and Oncology, Cancer Center, The University of California, Davis, Sacramento 95817, USA.

 The potential of American ginseng (AG) ( Panax quinquefolium), a commonly used herbal remedy believed to have anticarcinogenic effects, to prevent the development of mammary tumors was evaluated in a mouse model of dimethylbenzanthracene (DMBA)-induced mammary carcinoma. Ginsenosides, believed to be the active components of ginseng and that have a chemical structure similar to estradiol, have previously been shown to possess phytoestrogen-like qualities similar to the soy isoflavone genistein. The effects of AG, administered as powdered root, were compared to the selective estrogen receptor modulators tamoxifen and ospemifene. Eighty-three female SENCAR mice were divided into four treatment groups: control (N = 23), AG (N = 20), ospemifene (N = 20), and tamoxifen (N = 20). American ginseng, ospemifene, and tamoxifen were administered at a dose of 50 mg/kg/day orally by gavage, with the control mice receiving vehicle only. For the first 6 weeks, all mice received 20 microg/day DMBA in combination with their respective treatments. DMBA was then withdrawn, and daily treatments continued for a total of approximately 52 weeks. As expected, ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly reduced the incidence of mammary tumors compared to the control mice, which had a mammary tumor incidence of approximately 57%. The incidence of mammary carcinomas in the AG group was 40%, a reduction of approximately 29% compared to control. These results suggest that AG may still have the potential to prevent the development of mammary tumors in a chemically induced breast cancer mouse model, although the present study showed no significant difference between control and AG-treated mice.

  Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study.:Gynecol Endocrinol. 2007 Feb;23(2):117-22.Rotem C, Kaplan B.Felsenstein Medical Research Center, Beilinson Campus, Petah Tiqva, Israel.

 OBJECTIVE: To determine the efficacy and safety of the herbal formula Phyto-Female Complex (SupHerb, Netanya, Israel; ingredients: standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry) for the relief of menopausal symptoms. METHODS: A randomized, double-blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged 44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months. A structured questionnaire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period, followed by biochemical tests, breast check, and transvaginal ultrasonography. RESULTS: The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group. The effect of treatment improvements in menopausal symptoms increased over time; by 3 months there was a 73% decrease in hot flushes and a 69% reduction of night sweats, accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality. Hot flushes ceased completely in 47% of women in the study group compared with only 19% in the placebo group. There were no changes in findings on vaginal ultrasonography or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver enzymes or thyroid-stimulating hormone in either group. CONCLUSION: Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use.

  Application of atmospheric pressure chemical ionisation mass spectrometry in the identification and differentiation of Panax species.:Phytochem Anal. 2007 Mar;18(2):146-50.Leung KS, Chan K, Bensoussan A, Munroe MJ.Department of Chemistry, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, PR China. S9362284@hkbu.edu.hk

 An HPLC-MS method using an atmospheric pressure chemical ionisation (APCI) source has been developed to assist in the differentiation of three ginseng species: Panax quinquefolium (American ginseng), P. ginseng (Chinese ginseng) and P. notoginseng (sanqi) species. The differentiation method relies on the identification of ginsenosides Rf and F11 and notoginsenoside R1. R1 is observed in both P. notoginseng and Chinese ginseng, whilst F1, is found exclusively in the American species. The presence of these compounds permits the definitive identification of the species to be made. The APCI ionisation source has been employed to tackle the matrix interference in analysing Chinese medicinal materials and to minimise the associated matrix effects that are commonly encountered with other ionisation modes. Moreover, the method allows direct interface to conventional HPLC systems. More importantly, chemical reference standards of ginsenosides are not required in this method. This technique provides an alternative approach to analysing high molecular weight polar compounds that typically encountered in complex matrices of Chinese medicinal materials.

  Interference of Asian, American, and Indian (Ashwagandha) ginsengs in serum digoxin measurements by a fluorescence polarization immunoassay can be minimized by using a new enzyme-linked chemiluminescent immunosorbent or turbidimetric assay.:Arch Pathol Lab Med. 2007 Apr;131(4):619-21.Dasgupta A, Kang E, Olsen M, Actor JK, Datta P.Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 2.292, Houston, TX 77030, USA. Amitava.Dasgupta@uth.tmc.edu

 CONTEXT: Ginsengs are widely used by the general population. These herbs interfere with serum digoxin measurement using the fluorescence polarization immunoassay. OBJECTIVE: To assess potential interference of different ginsengs (Asian, American, and Indian, also known as Ashwagandha) in vitro and in vivo in a mouse model by using a new enzyme-linked chemiluminescent immunosorbent digoxin assay and an existing turbidimetric assay. Comparisons were made with the fluorescence polarization immunoassay. DESIGN: Aliquots of drug-free serum pools were supplemented with ginseng and apparent digoxin concentrations were measured using enzyme-linked chemiluminescent immunosorbent digoxin assay, turbidimetric assay, and fluorescence polarization immunoassay digoxin assays. Mice were fed with different ginseng preparations and apparent digoxin concentrations were measured 1 and 3 hours later. In a separate experiment, aliquots of serum digoxin pools were further supplemented with ginsengs and the serum digoxin concentrations were measured again. RESULTS: A significant apparent digoxin concentration was observed both in vitro and in vivo using the fluorescence polarization immunoassay, but no apparent digoxin concentration was observed using enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay. No interference was observed with enzyme-linked chemiluminescent immunosorbent digoxin assay and turbidimetric assay when digoxin serum pools were further supplemented with various ginsengs. CONCLUSIONS: It was concluded that both enzyme-linked chemiluminescent immunosorbent and turbidimetric digoxin assays are free from ginseng interferences.

  American ginseng (Panax quinquefolius L.) extract alters mitogen-activated protein kinase cell signaling and inhibits proliferation of MCF-7 cells.:J Exp Ther Oncol. 2007;6(2):147-55.King ML, Murphy LL.Department of Physiology, Southern Illinois University School of Medicine Carbondale, IL 62902-6523, USA.

 Ginseng has been shown to inhibit cancer cell proliferation and tumor growth, however the mechanisms underlying this inhibition have yet to be elucidated. An inhibitory effect of hot water-extracted American ginseng (Panax quinquefolius L.) root on cell proliferation was demonstrated using MCF-7 human breast cancer cells treated with a wide concentration range of the ginseng extract (GE) for 6 days. The effects of GE were concentration-dependent with an IC50 of 0.49 microg/microl and the minimum exposure time to elicit an inhibitory response was 24 hours. Using an antibody microarray, it was determined that several key cell survival proteins were altered in GE-treated cells, including several members of the mitogen-activated protein kinase (MAPK) family. A GE-induced decrease in phospho-MEK1/2 and -ERK1/2 and an increase in phospho-Raf-1 were observed and verified using Western blot analysis. Furthermore, mRNA and protein expression of the Raf-1 kinase inhibitor protein (RKIP) was shown to be transiently, yet significantly, upregulated following GE treatment. These results suggest that American ginseng may act to inhibit breast cancer cell proliferation by increasing the expression of RKIP, resulting in inhibition of the MAPK pathway. This novel mechanism has implications in the potential prevention and treatment of breast cancer.


  Pseudoginsenoside-F11 decreases morphine-induced behavioral sensitization and extracellular glutamate levels in the medial prefrontal cortex in mice.:Pharmacol Biochem Behav. 2007 Apr;86(4):660-6. Epub 2007 Feb 20.Hao Y, Yang JY, Wu CF, Wu MF.Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China.

 Morphine produces a variety of behavioral and biochemical changes related to its abuse. Our previous studies showed that Pseudoginsenoside-F11 (PF11), an ocotillol-type saponin existing in American ginseng, can antagonize pharmacological effects of morphine. To further investigate the effects of PF11 on morphine abuse and the underlying mechanisms, we tested the effects of PF11 on morphine-induced development of behavioral sensitization and alterations in glutamate levels in the medial prefrontal cortex (mPFC) in freely moving mice by using in vivo microdialysis. As the results shown, PF11 antagonized the development of behavioral sensitization and decrease of glutamate in the mPFC induced by morphine. Therefore, these findings suggest that PF11 may block the development of morphine-induced behavioral sensitization via its effect, at least partially, on the glutamatergic system in the mPFC.

  Utilization of RAPD markers to assess genetic diversity of wild populations of North American ginseng (Panax quinquefolium).:Planta Med. 2007 Jan;73(1):71-6.Lim W, Mudge KW, Weston LA.Department of Plant Breeding and Genetics, Cornell University, Ithaca, New York, USA.

 The Catskill Mountains of New York State are an important source of wild-collected American ginseng (Panax quinquefolium) and, increasingly, of woods-cultivated ginseng. The objective of this study was to assess genetic diversity among 9 different wild ginseng populations in and adjacent to the Catskill Mountain region of New York State and to compare these to wild populations from other states including Kentucky, Tennessee, North Carolina, Pennsylvania, and Virginia, and one cultivated population from Wisconsin. Randomly amplified polymorphic DNA (RAPD) markers were used to estimate the genetic distance among samples from the 15 populations. Pooled DNA from 10 plants of each of 8 New York populations was initially screened with 64 random primers; subsequently, the 15 primers that exhibited the greatest number of reproducible polymorphic markers were selected for further experimentation. Gel electrophoresis with the selected 15 primers produced 124 highly reproducible polymorphic bands. The ratio of discordant bands to total bands scored was used to estimate the genetic distance within and among populations. Multidimensional scaling (MDS) of the relation matrix showed distinctly separate clusters between New York and non-New York populations, indicating separation between these two groupings. The MDS analysis was confirmed using pooled chi-square tests for fragment homogeneity. This study shows that RAPD markers can be used as population-specific markers for Panax quinquefolium, and may eventually be utilized as markers for ginsenoside assessment.

  Protective effect of steamed American ginseng (Panax quinquefolius L.) on V79-4 cells induced by oxidative stress.:J Ethnopharmacol. 2007 May 22;111(3):443-50. Epub 2007 Jan 7.Kim KT, Yoo KM, Lee JW, Eom SH, Hwang IK, Lee CY.Korea Food Research Institute, San 46-1, Baekhyun-Dong, Bundang-Ku, Songnam-Si, Kyunggi-Do 463-746, Republic of Korea.

 Heat-processed Asian ginseng roots (Panax ginseng C.A. Meyer), also known as "red ginseng" in Asia, are reported to have more bioactivity than the no-processed white ginseng roots. Therefore, American fresh ginseng roots (Panax quinquefolius L.) were processed to the red ginseng and examined changes in bioactivity during heating process. The fresh America ginseng roots were steamed at 100 degrees C for 30, 60, 90 and 120 min, and their bioactivities were examined by analyzing the content of ginsenosides and total phenolics, and measuring DPPH and superoxide radical scavenging acivity and their protective effects on V79-4 cells viability and lipid peroxidation. The heating treatment proportionally increased total ginsenosides (4.97%, w/w) content compared with white ginseng (3.27%) and total phenolics from 444.5 mg GAE/100 g to 489.6-574.2 mg GAE/100 g. The antioxidant activity also increased from 285 mg/100 g (vitamin C equivalent) to 353-487 mg/100 g. Heated ginseng showed high levels of DPPH radical scavenging activity (59.5-88.5%) and the high level of superoxide radical scavenging activity (44.2-90.9%). The heated ginseng protected cell viability against H2O2-induced oxidative damage, and enhanced the activities of superoxide dismutase and catalase by dose dependently in V79-4 cells.

  Comparison of qualitative and quantitative in vitro ginsenoside production in callus cultures of three Panax species.:Planta Med. 1999 Jun;65(5):484-6.thur A, Mathur AK, Pal M, Uniyal GC.Division of Genetic Resources, Central Institute of Medicinal and Aromatic Plants, Lucknow, India. root@cimao.sirnetd.ernet.in

 The qualitative and quantitative difference in the various ginsenoside constituents of the crude butanol-soluble saponin fractions of callus cultures of two Indian species of Panax namely P. sikkimensis and P. pseudoginseng have been compared with that of P. quinquefolium (American ginseng). The 45-50 days old calli of the two Indian species, though found to accumulate crude ginsenoside at levels (0.9% and 1.1%, respectively) comparable to that in P. quinquefolium (1.2%), P. pseudoginseng callus showed high productivity of ginsenosides Rf (40.57%) and Ro (19.60%). P. quinquefolium calli on the other hand accumulated more of Rb and Rg group of ginsenosides but while the former appeared to be a Rg (2) accumulator the callus of the later was rich in the Rg (1) fraction.

  A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.:Int J Cancer. 2007 Apr 1;120(7):1523-8.Rebbeck TR, Troxel AB, Norman S, Bunin GR, DeMichele A, Baumgarten M, Berlin M, Schinnar R, Strom BL.Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. trebbeck@cceb.med.upenn.edu

 Hormone-related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population-based case-control study in 3 counties of the Philadelphia metropolitan area consisting of 949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p=0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p=0.003), ginseng (12.5% vs. 7.9%, p<0.001) and red clover (4.7% vs. 0.6%, p<0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22-0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer.


  Steamed American ginseng berry: ginsenoside analyses and anticancer activities.:J Agric Food Chem. 2006 Dec 27;54(26):9936-42.Wang CZ, Zhang B, Song WX, Wang A, Ni M, Luo X, Aung HH, Xie JT, Tong R, He TC, Yuan CS.Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, 5841 South Maryland Avenue, MC 4028, Chicago, Illinois 60637, USA.

 This study was designed to determine the changes in saponin content in American ginseng berries after treatment by heating and to assess the anticancer effects of the extracts. After steaming treatment (100-120 degrees C for 1 h, and 120 degrees C for 0.5-4 h), the content of seven ginsenosides, Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd, decreased; the content of five ginsenosides, Rh1, Rg2, 20R-Rg2, Rg3, and Rh2, increased. Rg3, a previously identified anticancer ginsenoside, increased significantly. Two hours of steaming at 120 degrees C increased the content of ginsenoside Rg3 to a greater degree than other tested ginsenosides. When human colorectal cancer cells were treated with 0.5 mg/mL steamed berry extract (120 degrees C 2 h), the antiproliferation effects were 97.8% for HCT-116 and 99.6% for SW-480 cells. At the same treatment concentration, the effects of unsteamed berry extract were 34.1% for HCT-116 and 4.9% for SW-480 cells. After staining with Hoechst 33258, apoptotic cells increased significantly by treatment with steamed berry extract compared with unheated extracts. Induction of apoptosis activity was confirmed by flow cytometry after staining with annexin V/PI. The steaming of American ginseng berries augments ginsenoside Rg3 content and increases the antiproliferative effects on two human colorectal cancer cell lines.

   Simultaneous determination of ginsenosides and polyacetylenes in American ginseng root (Panax quinquefolium L.) by high-performance liquid chromatography.:J Agric Food Chem. 2006 Nov 29;54(24):8995-9003.Christensen LP, Jensen M, Kidmose U.Departments of Food Science and of Horticulture, Danish Institute of Agricultural Sciences, Research Centre Aarslev, Kirstinebjergvej 10, DK-5792 Aarslev, Denmark. larsp.christensen@agrsci.dk

 A method for simultaneous determination of ginsenosides and polyacetylenes in Panax quinquefolium L. (American ginseng) roots was developed. The ginsenosides Rb1, Rb2, Rc, Rd, Re, Rg1, Ro, malonyl-Rb1, malonyl-Rc, and malonyl-Rd and the polyacetylenes falcarinol and panaxydol were extracted from fresh ginseng roots in a sequential extraction process with 100% methanol followed by 80% aqueous methanol and quantified simultaneously in extracts by high-performance liquid chromatography using diode array detection. Separations were achieved with a phosphate buffer-acetonitrile gradient system using an RP-C18 column. Except for Rd, the present extraction method resulted in similar or significantly higher concentrations of both ginsenosides and polyacetylenes in comparison to commonly used extraction methods for these compounds. The contents of polyacetylenes and ginsenosides were determined in the root hairs, lateral roots, and main roots of 6 year old ginseng plants. The total mean concentrations of ginsenosides and polyacetylenes in root hairs were 31.0 g/kg fresh weight (FW) and 2.6 g/kg FW, respectively, whereas the concentrations of these bioactive compounds in the main roots were significantly lower with total mean concentrations of 17.8 g/kg FW for ginsenosides and 0.6 g/kg FW for polyacetylenes. The concentration of individual and total ginsenosides and polyacetylenes did not differ significantly between main roots of different sizes. Consequently, it is possible to do quantitative screening for ginsenosides and polyacetylenes to breed ginseng roots with higher levels of bioactive compounds.

  Authentication of traditional Chinese medicine using infrared spectroscopy: distinguishing between ginseng and its morphological fakes.:J Biomed Sci. 2007 Mar;14(2):265-73. Epub 2006 Nov 16.Yap KY, Chan SY, Lim CS.Biosensors Group, Biomedical Engineering Research Centre, Nanyang Technological University, Singapore 637553, Singapore.

 The quality of pharmaceutical products such as ginseng is important for ensuring consumer safety and efficacy. Ginseng is an expensive herb, and adulteration with other cheaper products may occur. Quality assurance of ginseng is needed since many of its commercial products now come in various formulations such as capsules, powder, softgels and tea. Thus traditional means of authentication via smell, taste or physical appearance are hardly reliable. Herbs like ginseng tend to exhibit characteristic infrared fingerprints due to their different chemical constituents. Here we report for the first time a rapid means of distinguishing American and Asian ginsengs from two morphological fakes--sawdust and Platycodon grandiflorum, via pattern differences and principal component analysis of their infrared spectra. Our results show that ginseng can be distinguished from both sawdust and Platycodon grandiflorum, hence there is a potential of using infrared spectroscopy as a novel analytical technique in the authentication of ginseng.

  Chronic pretreatment with American ginseng berry and its polyphenolic constituents attenuate oxidant stress in cardiomyocytes.:Eur J Pharmacol. 2006 Dec 28;553(1-3):209-14. Epub 2006 Sep 30.Mehendale SR, Wang CZ, Shao ZH, Li CQ, Xie JT, Aung HH, Yuan CS.Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA. smehendale@dacc.uchicago.edu

 The acute anti-oxidant and protective effect of American ginseng berry extract (AGBE) has been demonstrated in cultured cardiomyocytes in our previous study. In the current study we evaluated if a chronic pretreatment of cultured cardiomyocytes with AGBE can alter the cellular antioxidant potential. Chick embryo cardiomyocytes were treated with AGBE (0.5-2.5 mg/ml) for up to 72 h. The treated cells were then exposed to exogenously added hydrogen peroxide (H(2)O(2); 500 microM). The oxidant-mediated injury was measured using a fluorescent probe 2',7'-dichlorofluorescin diacetate (DCFH/DA) while cell death was measured using propidium iodide (PI) staining. The non-treated (control) cells exposed to H(2)O(2) showed significant increase in DCF- and PI-mediated fluorescence suggesting significant oxidative injury and cell death. Pretreatment with AGBE demonstrated a significant attenuation of DCF fluorescence (p<0.005) with AGBE 0.5 mg/ml showing a 17% decrease, AGBE 1.0 mg/ml showing a 26% decrease, and AGBE 2.5 mg/ml showing a 49% decrease from control DCF fluorescence following a 72 h pretreatment. Cell death caused by H(2)O(2) was also significantly attenuated in AGBE-pretreated cells in a concentration- and time-dependent manner (p<0.005). We also demonstrated that active polyphenolic constituents in AGBE, caffeic acid and chlorogenic acid, appear to contribute significantly to AGBE's protective effects. Finally, catalase inhibition resulted in a significantly increased fluorescence in AGBE-treated cells compared to the control. The results suggest that pretreatment with AGBE upregulates peroxide detoxifying mechanisms, which could affect intracellular oxidant dynamics in cardiomyocytes.

  American Ginseng Stimulates Insulin Production and Prevents Apoptosis through Regulation of Uncoupling Protein-2 in Cultured beta Cells.:Evid Based Complement Alternat Med. 2006 Sep;3(3):365-72.Luo JZ, Luo L.

 American ginseng root displays the ability to achieve glucose homeostasis both experimentally and clinically but the unknown mechanism used by ginseng to achieve its therapeutic effects on diabetes limits its application. Disruption in the insulin secretion of pancreatic beta cells is considered the major cause of diabetes. A mitochondrial protein, uncoupling protein-2 (UCP-2) has been found to play a critical role in insulin synthesis and beta cell survival. Our preliminary studies found that the extracts of American ginseng inhibit UCP-2 expression which may contribute to the ability of ginseng protecting beta cell death and improving insulin synthesis. Therefore, we hypothesized that ginseng extracts suppress UCP-2 in the mitochondria of pancreatic beta cells, promoting insulin synthesis and anti-apoptosis (a programmed cell-death mechanism). To test the hypothesis, the serum-deprived quiescent beta cells were cultured with or without interleukin-1beta (IL-1beta), (200 pg ml(-1), a cytokine to induce beta cell apoptosis) and water extracts of American ginseng (25 mug per 5 mul administered to wells of 0.5 ml culture) for 24 h. We evaluated effects of ginseng on UCP-2 expression, insulin production, anti-/pro-apoptotic factors Bcl-2/caspase-9 expression and cellular ATP levels. We found that ginseng suppresses UCP-2, down-regulates caspase-9 while increasing ATP and insulin production/secretion and up-regulates Bcl-2, reducing apoptosis. These findings suggest that stimulation of insulin production and prevention of beta cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro-apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.


  Extraction-dependent effects of American ginseng (Panax quinquefolium) on human breast cancer cell proliferation and estrogen receptor activation.:Integr Cancer Ther. 2006 Sep;5(3):236-43.King ML, Adler SR, Murphy LL.Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 62901-6523, USA.

 HYPOTHESIS: Ginseng root extracts and the biologically active ginsenosides have been shown to inhibit proliferation of human cancer cell lines, including breast cancer. However, there are conflicting data that suggest that ginseng extracts (GEs) may or may not have estrogenic action, which might be contraindicated in individuals with estrogen-dependent cancers. The current study was designed to address the hypothesis that the extraction method of American ginseng (Panax quinquefolium) root will dictate its ability to produce an estrogenic response using the estrogen receptor (ER)-positive MCF-7 human breast cancer cell model. METHODS: MCF-7 cells were treated with a wide concentration range of either methanol-(alc-GE) or water-extracted (w-GE) ginseng root for 6 days. Cells were grown in media containing either normal or charcoal-stripped fetal calf serum to limit exposure to exogenous estrogen. Thus, an increase in MCF-7 cell proliferation by GE indicated potential estrogenicity. This was confirmed by blocking GE-induced MCF-7 cell proliferation with ER antagonists ICI 182,780 (1 nM) and 4-hydroxytamoxifen (0.1 microM). Furthermore, the ability of GE to bind ERalpha or ERbeta and stimulate estrogen-responsive genes was examined. RESULTS: Alc-GE, but not w-GE, was able to increase MCF-7 cell proliferation at low concentrations (5-100 microg/mL) when cells were maintained under low-estrogen conditions. The stimulatory effect of alc-GE on MCF-7 cell proliferation was blocked by the ER antagonists ICI 182,780 or 4-hydroxyta-moxifen. At higher concentrations of GE, both extracts inhibited MCF-7 and ER-negative MDA-MB-231 cell proliferation regardless of media conditions. Binding assays demonstrated that alc-GE, but not w-GE, was able to bind ERalpha and ERbeta. Alc-GE (50 microg/mL) also induced an approximate 2.5-fold increase in expression of the estrogen-responsive pS2 gene, as well as progesterone receptor (PgR) gene expression, whereas w-GE was without effect. CONCLUSION: These data indicate that low concentrations of alc-GE, but not w-GE, elicit estrogenic effects, as evidenced by increased MCF-7 cell proliferation, in a manner antagonized by ER antagonists, interactions of alc-GE with estrogen receptors, and increased expression of estrogen-responsive genes by alc-GE. Thus, discrepant results between different laboratories may be due to the type of GE being analyzed for estrogenic activity.

  Ginsenoside content and variation among and within American ginseng (Panax quinquefolius L.) populations.:Phytochemistry. 2006 Jul;67(14):1510-9. Epub 2006 Jul 12.Schlag EM, McIntosh MS.Department of Natural Resource Sciences and Landscape Architecture, University of Maryland, 2102 Plant Sciences Building #36, College Park, MD 20742, United States.

 The contents of five ginsenosides (Rg1, Re, Rb1, Rc and Rd) were measured in American ginseng roots collected from 10 populations grown in Maryland. Ginsenoside contents and compositions varied significantly among populations and protopanaxatriol (Rg1 and Re) ginsenosides were inversely correlated within root samples and among populations. The most abundant ginsenoside within a root and by population was either Rg1 or Re, followed by Rb1. Ginseng populations surveyed grouped into two chemotypes based on the relative compositions of Rg1 and Re. Four populations, including the control population in which plants were grown from TN and WI seed sources, contained roots with the recognized chemotype for American ginseng of low Rg1 composition relative to Re. The remaining 6 populations possessed roots with a distinctive chemotype of high relative Rg1 to Re compositions. Chemotype did not vary by production type (wild versus cultivated) and roots within a population rarely exhibited chemotypes different from the overall population chemotype. These results provide support for recent evidence that relative Rg1 to Re ginsenoside contents in American ginseng roots vary by region and that these differences are likely influenced more by genotype than environmental factors. Because the physiological and medicinal effects of different ginsenosides differ and can even be oppositional, our findings indicate the need for fingerprinting ginseng samples for regulation and recommended usage. Also, the High Rg1/Low Re chemotype discovered in MD could potentially be used therapeutically for coronary health based on recent evidence of the positive effects of Rg1 on vascular growth.

  Cisplatin's tumoricidal effect on human breast carcinoma MCF-7 cells was not attenuated by American ginseng.:Cancer Chemother Pharmacol. 2007 Feb;59(3):369-74. Epub 2006 Jun 24.Aung HH, Mehendale SR, Wang CZ, Xie JT, McEntee E, Yuan CS.Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 4028, Chicago, IL 60637, USA.

 PURPOSE: We previously observed that American ginseng berry and ginsenoside Re attenuated cisplatin-induced emesis in a rat model, suggesting that the herb may have a value in treating chemotherapy-induced nausea/vomiting. However, it is not clear whether consuming ginseng concurrently with chemotherapy affects the efficacy of chemotherapeutic agents. In this study, we explored if the ginseng extract and its constituents, ginsenosides Rb1, Rb3, and Re, alter tumoricidal activity of cisplatin in human cancer cells. METHODS: Tumoricidal effects of cisplatin, and/or American ginseng berry extract (AGBE) and ginsenosides Rb1, Rb3, and Re, on human breast carcinoma MCF-7 cells were measured as cell proliferation in vitro. Cell counts were performed in MCF-7 cells pretreated with test agents for 72 h. RESULTS: Cisplatin decreased MCF-7 cell proliferation significantly in a concentration-dependent manner. Compared to control group, cisplatin reduced the cell proliferations to 56.5+/-3.3% at 1 microg/ml, to 36.6+/-2.4% at 5 microg/ml, and to 26.9+/-2.4% at 15 microg/ml (P<0.01). AGBE also inhibited the cell proliferation significantly, although in a less extended manner. When the berry extract at 0.5 mg/ml was used with cisplatin at 1 microg/ml, a significant enhancement of cisplatin's activity was observed (35.8+/-2.5%; P<0.05). We also observed that Rb1 did not change cisplatin's activity; Rb3, at a higher concentration, increased cisplatin's anti-proliferation activity (48.0+/-1.2%; P<0.05); Re increased cisplatin's activity (Re 0.1 mg/ml, 48.0+/-2.8%; Re 0.3 mg/ml, 31.9+/-2.2%, P<0.01). CONCLUSION: Our data suggest that AGBE and the tested ginsenosides do not attenuate cisplatin's tumoricidal activity in MCF-7 cells, but in fact may actually enhance it. Additionally, the ginseng extract and ginsenoside Re by themselves exerted anti-proliferative activity against MCF-7 cells. The herb might potentially serve a complementary role with the chemotherapeutic agents in treating cancer, in addition to decreasing chemotherapy-induced nausea/vomiting.

  Anticonvulsant and neuroprotective effects of ginsenosides in rats.:Epilepsy Res. 2006 Aug;70(2-3):244-56. Epub 2006 Jun 16. Lian XY, Zhang Z, Stringer JL. Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

 A partially purified extract from American ginseng has been shown to have anticonvulsant activity. To identify the active components in this extract, the activities of the individual ginsenosides (Rb(1), Rb(3) and Rd), mixtures of the purified ginsenosides and a newly prepared Rb fraction were determined. One hour after treatment with vehicle or one of the ginseng products, seizures were induced in adult, Sprague-Dawley rats with kainic acid (KA, 10 mg/kg), pilocarpine (300 mg/kg) or pentylenetetrazole (PTZ, 50mg/kg i.p. or 90 mg/kg s.c.). Time to seizure onset, duration of seizure activity and seizure severity were determined. Weight change and neuronal damage were assessed 24h after administration of KA or pilocarpine. Mixtures of purified Rb(1), Rb(3) with or without Rd had significant anticonvulsant effects in all three models of acutely induced seizures demonstrating that the ginsenosides are the active components in the Rb extract. The individual ginsenosides significantly increased the latency to onset of seizures after administration of kainic acid. Since no one individual ginsenoside accounted for the majority of the activity of the Rb extract, the results suggest that the most effective anticonvulsant product is a combination of ginsenosides. In addition, all of the ginseng products had significant neuroprotective activity beyond the reduction in seizure severity and duration.

  Efficacy of COLD-fX in the prevention of respiratory symptoms in community-dwelling adults: a randomized, double-blinded, placebo controlled trial.:J Altern Complement Med. 2006 Mar;12(2):153-7.McElhaney JE, Goel V, Toane B, Hooten J, Shan JJ.Center for Immunotherapy of Cancer and Infectious Diseases, School of Medicine, University of Connecticut, Farmington, CT, USA.

 BACKGROUND: COLD-fX (CVT-E002), a proprietary extract of the roots of North American ginseng (Panax quinquefolium), rich in poly-furanosyl-pyranosyl-saccharides, has been found efficacious in the prevention of respiratory infections in institutionalized seniors and healthy adults. OBJECTIVE: We examined the efficacy of COLD-fX in the prevention of acute respiratory illness (ARI) in community dwelling seniors. DESIGN: This was a randomized, double-blind, placebo controlled trial. INTERVENTION: The participants were asked to take 2 capsules/day of either COLD-fX or placebo (200 mg/ capsule) for a period of 4 months. SUBJECTS: A total of 43 community-dwelling adults aged 65 years or older were recruited. Following one month of intervention, subjects were immunized with influenza vaccine. OUTCOME MEASURES: Subjects recorded the incidence and duration of respiratory symptoms during the study. They also recorded the incidence of adverse events during the study. RESULTS: The frequency and duration of ARI during the first two months of the study was found to be similar in the two groups. However, during the last 2 months (November and December) significantly fewer subjects in the COLD-fX group 32% reported ARI compared to the placebo group 62%. The duration of symptoms during the last 2 months was significantly shorter in the COLD-fX group than the placebo group (5.6 days in the COLD-fX group vs 12.6 days in the placebo group). There was no influenza illness circulating in the community during the period of the study. CONCLUSIONS: Ingestion of COLD-fX by immunocompetent seniors during an early "cold and flu" season reduced the relative risk and duration of respiratory symptoms by 48% and 55%, respectively. Daily COLD-fX administration can thus be a safe, natural therapeutic means for the prevention of ARI in healthy seniors.


  Saponins composition in American ginseng leaf and berry assayed by high-performance liquid chromatography.:J Agric Food Chem. 2006 Mar 22;54(6):2261-6.Wang CZ, Wu JA, McEntee E, Yuan CS.Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, Illnois 60637, USA.

 The root of American ginseng is a commonly used herbal medicine in the United States. However, the compositions of American ginseng leaves and berries are not clear to date. In this study, we improved a method for the analysis of 12 ginsenosides based on solid phase extraction and high-performance liquid chromatography-ultraviolet. Good resolution was obtained for all tested ginsenosides: Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, Rg2, 20(R)-Rg2, Rg3, Rh1, and Rh2. Ginsenosides Rh1, Rg2, and 20(R)-Rg2 were easily separated with this column. The modified gradient elution program resulted in satisfactory linearity and precision. Solid phase extraction made the analysis accurate and efficient. Other investigators recently observed that ginsenoside Rb3 is a potent neuroprotective compound; it can promote learning and memory. In this report, we found that the major ginsenoside in American ginseng leaves and berries was ginsenoside Rb3, while Rb3 only had limited amounts in the root of American ginseng and other species of the Panax genus. Ginsenoside Rb3 was quantified as 4.71% in American ginseng leaves and 5.35% in berries, suggesting that American ginseng leaves and berries are new sources of ginsenoside Rb3.

  Long-term intake of North American ginseng has no effect on 24-hour blood pressure and renal function.:Hypertension. 2006 Apr;47(4):791-6. Epub 2006 Mar 6.Stavro PM, Woo M, Leiter LA, Heim TF, Sievenpiper JL, Vuksan V.Risk Factor Modification Centre, St Michael's Hospital, Toronto, Ontario, Canada.

 Ginseng is consumed by 10% to 20% of adults in Asia and by up to 5% in Western countries. Despite observational evidence suggesting a link between its intake and the development of hypertension, there remains no long-term scrutiny for its effect on blood pressure (BP). We therefore undertook a randomized, placebo-controlled, double-blinded, crossover trial in 52 hypertensive individuals to determine the effect of 12-week North American ginseng intake on 24-hour BP; we also measured serum cystatin C as a marker of renal function. After a 4-week placebo run-in, we randomly assigned 52 participants to 3 g/day of ginseng or placebo for 12 weeks. This was followed by an 8-week washout and a subsequent 12-week period in which the opposite treatment was administered. At run-in and at weeks 0 and 12 of each treatment period, participants were fitted with an ambulatory BP monitor to assess 24-hour BP. The primary outcome was the treatment difference at week 12 in mean 24-hour systolic BP. Secondary outcomes were treatment differences at week 12 in other ambulatory BP parameters and serum cystatin C. Forty participants (77%) completed the trial, with 3 removed from main analysis (n=2, antihypertensive drug changes; n=1, incomplete ambulatory monitoring). In the remaining 37, 12-week ginseng treatment was associated with a neutral effect on all ambulatory BP parameters compared with placebo; an intention-to-treat analysis supported this. Ginseng did not affect serum cystatin C level. Overall, long-term ginseng use had no effect on 24-hour BP and renal function in hypertensive individuals.

  A method for the analysis of ginsenosides, malonyl ginsenosides, and hydrolyzed ginsenosides using high-performance liquid chromatography with ultraviolet and positive mode electrospray ionization mass spectrometric detection.:J AOAC Int. 2006 Jan-Feb;89(1):16-21.Sloley BD, Lin YC, Ridgway D, Semple HA, Tam YK, Coutts RT, Lobenberg R, Tam-Zaman N.Novokin Biotech Inc., Analytical Department, 108 Advanced Technology Centre, 9650 20th Ave NW, Edmonton, Alberta, Canada. duff@novokin.com

 A high-performance liquid chromatographic separation coupled to diode array absorbance and positive mode electrospray mass spectrometric detection has been developed for the analysis of ginsenosides, malonyl ginsenosides, and hydrolyzed ginsenosides in extracts of Asian ginseng (Panax ginseng) and American ginseng (P. quinquefolius). The method is capable of separating, identifying, and quantifying the predominant ginsenosides found in heated alcoholic extracts of Asian and American ginseng roots routinely sold as nutraceuticals. It also separates and identifies the malonyl ginsenosides often found in cold alcoholic extracts of ginseng root and has the potential to quantify these compounds if pure standards are available. Furthermore, it can separate and identify ginsenoside hydrolysis products such as those readily produced in situations mimicking gastric situations, including those used for dissolution studies (i.e., 0.1 N HCl, 37 degrees C).

  Antioxidant effects of ginsenoside Re in cardiomyocytes.:Eur J Pharmacol. 2006 Feb 27;532(3):201-7. Epub 2006 Feb 21.Xie JT, Shao ZH, Vanden Hoek TL, Chang WT, Li J, Mehendale S, Wang CZ, Hsu CW, Becker LB, Yin JJ, Yuan CS.Tang Center for Herbal Medicine Research, Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA.

 We have previously demonstrated that American ginseng berry extract exhibited significant protection against oxidant-mediated injury in cardiomyocytes. To extend this work, we sought to investigate the antioxidant effects of Re, a protopanaxatriols-type and single chemical integrant present in American ginseng berry extract, using the same chick cardiomyocyte model of oxidant injury as well as ESR spectroscopy in a cell-free chemical system. In cells exposed to 2 h of H2O2 (0.5 mM), pretreatment with Re (0.05, 0.1, or 0.5 mg/ml for 2 h) significantly attenuated 2',7'-dichlorofluorescein (DCF) fluorescence by 51% (from 1345+/-67 to 658+/-46 a.u., P<0.001), and remarkably reduced cell death (from 51.5+/-3.0% to 11.8+/-1.5%, P<0.001, compared to the control). Similar results were also observed in cells exposed to antimycin A (100 microM), a mitochondrial electron transport chain site III inhibitor which increases endogenous oxidative stress. In the ESR study, however, Re failed to reduce the formation of the superoxide/DMPO adduct and DPPH radicals. These results suggest that ginsenoside Re functions as an antioxidant, protecting cardiomyocytes from oxidant injury induced by both exogenous and endogenous oxidants, and that its protective effects may be mostly attributed to scavenging H2O2 and hydroxyl radicals.

  Effectiveness of activated charcoal and equilibrium dialysis in removing Asian, American, Siberian and Indian ginseng from human serum.:Clin Chim Acta. 2006 May;367(1-2):144-9. Epub 2006 Jan 31.Dasgupta A, Veras E.Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 2.292, Houston, TX 77030, United States. Amitava.Dasgupta@uth.tmc.edu

 BACKGROUND: Ginsengs are used by the general population worldwide and toxicity of various ginsengs has been reported. We studied the effectiveness of activated charcoal and in vitro equilibrium dialysis for removal of Asian, American, Siberian and Indian ginseng from human serum by measuring digoxin-like immunoreactivity using the fluorescence polarization immunoassay. METHODS: 1xPBS (phosphate buffered saline) or drug free serum pool was supplemented with Asian, American, Siberian or Indian ginseng extract in amount expected in overdose. The aliquots of supplemented buffer or serum pool were treated with activated charcoal (15 or 50 mg of activated charcoal/ml of buffer/serum) for 5, 10, 20 and 30 min and digoxin-like immunoreactivities were compared with the original specimens. Other drug free serum pools were also supplemented with various ginsengs and then passed through a small column packed with activated charcoal or subjected to in vitro equilibrium dialysis against phosphate buffer at pH 7.4. RESULTS: Complete removal of digoxin-like immunoreactivity from buffer solution or serum pool supplemented with various ginsengs can be achieved by treatment with activated charcoal. Moreover, when serum pools supplemented with various ginsengs were passed through columns packed with activated charcoal, we observed complete removal of digoxin-like immunoreactivity. In addition, significant removal of digoxin-like immunoreactivity was observed when serum pools supplemented with ginsengs were subjected to equilibrium dialysis for 24 h. CONCLUSIONS: Removal of digoxin-like immunoreactivity from buffer solution or serum due to the presence of ginsengs can be achieved by treatment with activated charcoal in vitro but complete removal of digoxin-like activity from serum is not possible even after 24 h of equilibrium dialysis.


  Menopause: a review of botanical dietary supplements.:Am J Med. 2005 Dec 19;118 Suppl 12B:98-108. Review.Low Dog T.Program in Integrative Medicine, Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona, USA. tlowdog@ahsc.arizona.edu

 Since the release of the Women's Health Initiative (WHI) findings, an increasing number of dietary supplement products specifically targeting women in menopause have appeared in the American marketplace. This growth highlights the need for a critical evaluation of the tolerability and effectiveness of these products. The purpose of this article is to assess the evidence for safety and benefit of botanical monopreparations used for relief of menopause-related symptoms. The Cochrane Library and Medline databases were searched from January 1966 to October 2004, using a detailed list of terms related to botanicals and menopausal symptoms. Studies were considered eligible (1) if they were controlled trials of a botanical monopreparation administered orally for a minimum of 6 weeks to perimenopausal or postmenopausal women with hot flashes and (2) if they included a placebo or comparative treatment arm. Topical preparations, botanical combinations, and dietary interventions, such as soy food or protein, were not included. No language restrictions were imposed on the search. A total of 19 studies met the inclusion criteria. The majority of studies indicate that extract of black cohosh (Actaea racemosa L.) improves menopause-related symptoms; however, methodologic shortcomings in the trials were identified. To date, 4 case reports of possible hepatotoxicity have been published, although previous safety reviews suggest that black cohosh is well tolerated and that adverse events are rare when it is used appropriately. The results of 6 clinical studies on soy (Glycine max L.) isoflavone extracts are mixed. Moreover, the composition and dose of soy supplements varies widely across studies, making comparisons and definitive conclusions difficult. One study challenged the long-term safety of high-dose soy isoflavone extract (150 mg/day for 5 years) on the uterine endometrium. Clinical data from 5 controlled trials assessing the efficacy of semipurified isoflavone red clover (Trifolium pratense L.) leaf extracts to reduce hot flash frequency and severity or to relieve symptoms associated with the domains of the Greene Menopausal Symptom Scale are contradictory. The largest study showed no benefit for reducing symptoms associated with menopause for 2 different red clover isoflavone products compared with placebo. No significant adverse events have been reported in the literature. Single clinical trials do not support the use of dong quai (Angelica sinensis L.), ginseng (Panax ginseng C.A. Mey), or evening primrose seed oil (Oenothera biennis L.) for improving menopausal symptoms. We conclude that black cohosh extracts appear to ease menopausal symptoms; ongoing studies funded by the National Institutes of Health (NIH) will provide more definitive safety and efficacy data. Soy isoflavone extracts appear to have minimal to no effect, although definitive conclusions are difficult given the wide variation in product composition and dose. Long-term safety of higher dosage (150 mg/day) soy isoflavone extracts is uncertain. Semipurified isoflavone red clover leaf extracts have minimal to no effect in reducing menopausal symptoms. Dong quai, ginseng extract, and evening primrose seed oil appear to be ineffective in ameliorating menopausal symptoms at the dosages and in the preparations used in these studies.

  Simplified extraction of ginsenosides from American ginseng (Panax quinquefolius L.) for high-performance liquid chromatography-ultraviolet analysis.:J Agric Food Chem. 2005 Dec 28;53(26):9867-73.Corbit RM, Ferreira JF, Ebbs SD, Murphy LL.Department of Plant Biology, Southern Illinois University Carbondale, Carbondale, Illinois 62901, USA.

 Four methods were tested for extraction and recovery of six major ginsenosides (Rb1, Rb2, Rc, Rd, Re, and Rg1) found in roots of American ginseng (Panax quinquefolius): method A, sonication in 100% methanol (MeOH) at room temperature (rt); method B, sonication in 70% aqueous MeOH at rt; method C, water extraction (90 degrees C) with gentle agitation; and method D, refluxing (60 degrees C) in 100% MeOH. After 0.5-1 h, the samples were filtered and analyzed by high-performance liquid chromatography (HPLC)-UV. A second extraction by methods C and D was done, but 85-90% of ginsenosides were obtained during the first extraction. Lyophilization of extracts did not influence ginsenoside recovery. Method D resulted in the highest significant recoveries of all ginsenosides, except Rg1. Method C was the next most effective method, while method A resulted in the lowest ginsenoside recoveries. Method B led to similar recoveries as method C. All methods used one filtration step, omitted time-consuming cleanup, but maintained clear peak resolution by HPLC, and can be used for quantitative screening of ginsenosides from roots and commercial ginseng preparations.

  Quality and safety assessment of ginseng extracts by determination of the contents of pesticides and metals.:Food Addit Contam. 2005 Dec;22(12):1224-30.Durgnat JM, Heuser J, Andrey D, Perrin C.Quality & Safety Assurance Department, Nestl¨¦ Research Center, PO Box 44, Vers-chez-les-Blanc, CH-1000 Lausanne 26, Switzerland.

 Ginseng extracts are available as ingredients for improving energy and vitality and can be used in functional foods and as flavouring ingredients. A survey was been performed to determine the content of pesticides and toxic metals in ginseng extracts. Forty-seven samples from 20 suppliers, including both Panax ginseng C. A. Meyer (Asian ginseng) and P. quinquefolius (American ginseng) species, were analysed for arsenic content and for the following metals: aluminium, molybdenum, chromium, copper, magnesium, zinc, cadmium, mercury and lead, while pesticide residues were analysed in 30 samples from 17 suppliers. The results showed that 24 samples (80%) contained pesticides above the detection limit and 13 samples (43%) did not comply with the maximum residue limits (MRL) for total quintozene, hexachlorobenzene, total hexachlorocyclohexane, lindane, total heptachlor, e-chlorpyrifos and folpet, imposed for botanical extracts. Total quintozene, hexachlorobenzene, total hexachlorocyclohexane and lindane were present in all contaminated samples and exceeded the MRL in eleven samples, with levels up to 55 and 30 times their respective MRL. Cadmium (<0.05-259 microg kg(-1)), mercury (<0.3-72 microg kg(-1)), lead (3-2710 microg kg(-1)) and arsenic (<0.3-918 microg kg(-1)) were present in most samples at concentrations lower than the MRL imposed for flavouring substances. Among the other elements, aluminium (0.3-1068 mg kg(-1)) was the most abundant.

  Ginsenoside extraction from Panax quinquefolium L. (American ginseng) root by using ultrahigh pressure.:J Pharm Biomed Anal. 2006 Apr 11;41(1):57-63. Epub 2005 Dec 5.Zhang S, Chen R, Wu H, Wang C.College of Biological and Agricultural Engineering, Jilin University, Changchun, China.

 A new method of ultrahigh pressure extraction (UPE) was used to extract the ginsenosides from Panax quinquefolium L. (American ginseng) root at room temperature. Several solvents, including water, ethanol, methanol, and n-butanol were used in the UPE. The ginsenosides were quantified by a HPLC equipped with UV-vis detector. The results showed that ethanol is the most efficient solvent among the used ones. Compared with other methods, i.e., Soxhlet extraction, heat reflux extraction, ultrasound-assisted extraction, microwave-assisted extraction, and supercritical CO2 extraction, the UPE has the highest extraction yield in the shortest time. The extraction yield of 0.861% ginsenoside-Rc in 2 min was achieved by the UPE, while the yields of 0.284% and 0.661% were obtained in several hours by supercritical CO2 extraction and the heat reflux extraction, respectively.

  The influence of lead and arsenite on the inhibition of human breast cancer MCF-7 cell proliferation by American ginseng root (Panax quinquefolius L.).:Life Sci. 2006 Feb 16;78(12):1336-40. Epub 2005 Nov 9.Corbit R, Ebbs S, King ML, Murphy LL.Department of Plant Biology, Southern Illinois University Carbondale, Carbondale, IL 62901, USA.

 American ginseng root (Panax quinquefolius) has a number of purported therapeutic effects, including inhibition of cancer cell proliferation. The ability of environmentally relevant heavy metals to alter ginseng effects on cancer cell growth was the subject of this study. A water extract of American ginseng root was applied alone or in combination with physiologically relevant doses of either lead (Pb) or arsenite to MCF-7 breast cancer cells in vitro and effects on cell proliferation were determined. Ginseng alone produced a significant dose-dependent inhibition of MCF-7 cell proliferation starting at 0.5 mg ml(-1). Treatment of MCF-7 cells with 2.5 microM arsenite significantly decreased MCF-7 cell proliferation (p < 0.01). When cells were treated with arsenite (1.25 or 2.5 microM) in combination with ginseng extract (0.5 mg ml(-1)), there was an apparent synergistic inhibition of cell proliferation. Treatment of MCF-7 breast cancer cells with 50 microM Pb significantly decreased cell proliferation relative to control (p < 0.01), and concomitant ginseng and Pb treatment did not lead to a further decrease. These results suggest that contaminant heavy metals, some of which have been detected in ginseng root extracts or commercial ginseng preparations, may alter the biological activity of ginseng.


  High efficiency plant production of North American ginseng via somatic embryogenesis from cotyledon explants.:Plant Cell Rep. 2006 Mar;25(3):166-73. Epub 2005 Nov 11.Zhou S, Brown DC.Southern Crop Protection and Food Research Centre, Agriculture and Agri-Food Canada, 1391 Sandford St., London, ON N5V 4T3, Canada. browndc@agr.gc.ca

 An efficient in vitro protocol for plant production of North American ginseng has been established. The pretreatment of cotyledon explants with 1.0 M sucrose at 4 degrees C resulted in an improvement of embryo quality and, combined with a higher sucrose content (7%) in induction medium, improved the embryogenesis frequency from 40% to 75% and the number of embryos per explant from 10 to 21. The frequency of secondary embryogenesis from somatic embryo-derived tissues cultured on MS medium with 1.0 mg l(-1) 2, 4-D and 1.0 mg l(-1) NAA is up to 90%. Somatic embryos can further develop to maturity on SH medium supplemented with 1% activated charcoal and half of them can germinate. About 85% of the germinated embryos will convert into plants with well-developed taproot systems on 1/2 SH medium with 0.5% activated charcoal. The growth chamber and field establishment rates were 95.6 and 93.7%, respectively. The plants transplanted to growth chambers and field plots appear normal.

  Isolation and determination of ginsenosides in American ginseng leaves and root extracts by LC-MS.:Anal Bioanal Chem. 2005 Dec;383(7-8):1098-105. Epub 2005 Nov 9.Ligor T, Ludwiczuk A, Wolski T, Buszewski B.Department of Environmental Chemistry and Ecoanalytics, Faculty of Chemistry, Nicolaus Copernicus University, 7 Gagarina Street, 87100, Toru¨½, Poland. bbusz@chem.uni.torun.pl

 Ginseng saponins (ginsenosides) were extracted from the root and leaves of locally cultivated American ginseng (Panax quinquefolium L.). For the isolation of compounds from plant samples three different extraction methods were utilized: accelerated solvent extraction, the ultrasound-assisted solvent extraction and mechanical shaking assisted solvent extraction. The separation of compounds was achieved with a water-acetonitrile gradient system using a C18 reversed-phase column. Target compounds were identified in MS(2) and MS(3) experiments. The relative distribution of these ginsenosides in each root and leaf extract was established. The limit of detection of the method was less than 30 ng/ml. Recovery of ginseng saponins in spiked samples exceeded 80%, while the relative standard deviation ranged from 7.1 to 9.1%. The total concentrations of ginsenosides were 41 and 13 mg/g in root and leaves.

  Effects of population, age, and cultivation methods on ginsenoside content of wild American ginseng (Panax quinquefolium).:J Agric Food Chem. 2005 Nov 2;53(22):8498-505.Lim W, Mudge KW, Vermeylen F.Department of Horticulture, 13 Plant Science Building, Cornell University, Ithaca, NY 14853, USA.

 Genotype and environmental effects on ginsenoside content among eight wild populations of American ginseng (Panax quinquefolium) were investigated. Root concentrations of six ginsenosides were determined at the time of collection of plants from the wild (T0) and 2 years (T2) after transplanting roots from each of the eight populations to each of two different forest garden locations. Both location and population had significant effects on root and shoot growth. Overall, ginsenoside Rb1 was most abundant, followed by Rg1 and Re. Concentrations of Rg1 and Re were inversely related among and within populations. The relative ranking of populations differed depending upon the particular ginsenoside and sampling time. The relative importance of genotype and environment was not the same for all ginsenosides. Ginsenoside Re was influenced by population but not location, whereas Rb1, Rc, and Rb2 were influenced only by location (environment), while Rg1 and Rd were influenced by both. Ginsenoside levels were consistently lower, but growth was consistently higher at the more intensively managed garden location.

  Efficacy of an extract of North American ginseng containing poly-furanosyl-pyranosyl-saccharides for preventing upper respiratory tract infections: a randomized controlled trial.:CMAJ. 2005 Oct 25;173(9):1043-8.Predy GN, Goel V, Lovlin R, Donner A, Stitt L, Basu TK.Capital Health, Edmonton, Alta.

 BACKGROUND: Upper respiratory tract infections are a major source of morbidity throughout the world. Extracts of the root of North American ginseng (Panax quinquefolium) have been found to have the potential to modulate both natural and acquired immune responses. We sought to examine the efficacy of an extract of North American ginseng root in preventing colds. METHODS: We conducted a randomized, double-blind, placebo-controlled study at the onset of the influenza season. A total of 323 subjects 18-65 years of age with a history of at least 2 colds in the previous year were recruited from the general population in Edmonton, Alberta. The participants were instructed to take 2 capsules per day of either the North American ginseng extract or a placebo for a period of 4 months. The primary outcome measure was the number of Jackson-verified colds. Secondary variables measured included symptom severity, total number of days of symptoms and duration of all colds. Cold symptoms were scored by subjects using a 4-point scale. RESULTS: Subjects who did not start treatment were excluded from the analysis (23 in the ginseng group and 21 in the placebo group), leaving 130 in the ginseng group and 149 in the placebo group. The mean number of colds per person was lower in the ginseng group than in the placebo group (0.68 [standard deviation (SD) 0.82] v. 0.93 [SD 0.91], difference 0.25%, 95% confidence interval [CI] 0.04-0.45). The proportion of subjects with 2 or more Jackson-verified colds during the 4-month period (10.0% v. 22.8%, 12.8% difference, 95% CI 4.3-21.3) was significantly lower in the ginseng group than in the placebo group, as were the total symptom score (77.5 [SD 84.6] v. 112.3 [SD 102.5], difference 1.5%, 95% CI 1.2-2.0) and the total number of days cold symptoms were reported (10.8 [SD 9.7] v. 16.5 [SD 13.8] days, difference 1.6%, 95% CI 1.3-2.0) for all colds. INTERPRETATION: Ingestion of a poly-furanosyl-pyranosyl-saccharide-rich extract of the roots of North American ginseng in a moderate dose over 4 months reduced the mean number of colds per person, the proportion of subjects who experienced 2 or more colds, the severity of symptoms and the number of days cold symptoms were reported.

  American ginseng supplementation attenuates creatine kinase level induced by submaximal exercise in human beings.:World J Gastroenterol. 2005 Sep 14;11(34):5327-31.Hsu CC, Ho MC, Lin LC, Su B, Hsu MC.Graduate Institute of Sports Science, National College of Physical Education and Sports, Taoyuan County, Taiwan, China.

 AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance. METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo) and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk. They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover, the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise, immediately after exercise, and 20, 40, 60, and 120 min after exercise. RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen. CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.


  Determination of major ginsenosides in Panax quinquefolius (American ginseng) using high-performance liquid chromatography.:Phytochem Anal. 2005 Jul-Aug;16(4):272-7.Wang A, Wang CZ, Wu JA, Osinski J, Yuan CS.Tang Center for Herbal Medicine Research, The University of Chicago, Chicago, IL 60637, USA.

 In order to determine the active ingredients in root extracts of Panax quinquefolius (American ginseng), a gradient HPLC method involving UV photodiode array detection was applied to separate and quantify simultaneously the ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf and Rg1. All ginseng saponins were baseline-resolved under the selected conditions, and the detection limits were 1.0 microg/mL or less. The method has been applied to analyse ginsenosides extracted from American ginseng cultivated in both Wisconsin and Illinois. Ginsenosides Re and Rb1 were the two main ginseng saponins in the root. The amounts of Re in 5- and 7-year Illinois-cultivated samples were greater than those found in ginseng cultivated for 3 or 4 years in Wisconsin, whereas the levels of Rb1 were greater in the younger Wisconsin samples.

  Effect of Brazilian, Indian, Siberian, Asian, and North American ginseng on serum digoxin measurement by immunoassays and binding of digoxin-like immunoreactive components of ginseng with Fab fragment of antidigoxin antibody (Digibind).:Am J Clin Pathol. 2005 Aug;124(2):229-36.Dasgupta A, Reyes MA.Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, 77030, USA.

 We compared Brazilian, Indian, Siberian, Asian, and North American ginseng for potential interference with 3 digoxin immunoassays: fluorescence polarization (FPIA), microparticle enzyme (MEIA), and Tina-quant (Roche Diagnostics, Indianapolis, IN). We supplemented aliquots of a drug-free serum pool with ginseng extracts representing expected in vivo concentrations and overdose. We observed apparent digoxin-like immunoreactivity with FPIA, modest immunoreactivity with MEIA, and no apparent digoxin immunoreactivity with the Tina-quant with all ginsengs except Brazilian, which showed no immunoreactivity with any assay. When aliquots of serum pools prepared from patients receiving digoxin were supplemented with ginsengs, we observed falsely elevated digoxin values with FPIA, falsely lower digoxin values (negative interference) with MEIA, and no interference with the Tina-quant. Digoxin-like immunoreactive components of various ginsengs have moderate protein binding; monitoring free digoxin concentrations does not eliminate such interference. We also observed that Digibind (Burroughs Wellcome, Research Triangle Park, NC) can bind free digoxin-like immunoreactive components of ginsengs; such effects can be monitored by measuring apparent free digoxin concentrations. Indian, Asian, and North American ginsengs interfere with serum digoxin measurement by FPIA and MEIA; the Tina-quant is free of such interference. Digibind can bind free digoxin-like immunoreactive components of ginseng.

  North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension.:Hypertension. 2005 Aug;46(2):406-11. Epub 2005 Jul 5.Stavro PM, Woo M, Heim TF, Leiter LA, Vuksan V.Risk Factor Modification Centre, St. Michael's Hospital, 61 Queen St E, 6th Floor, Suite 138, Toronto, Ontario, M5C 2T2, Canada.

 An early observational study suggested that ginseng could elevate blood pressure. This caused concern because 4.5% of American adults use ginseng, with a popular choice being North American ginseng. To date, North American ginseng lacks hemodynamic evaluation; therefore, we conducted a randomized, double-blinded, controlled trial to investigate its effect on blood pressure in 16 hypertensive individuals (mean+/-SD age 61.1+/-8.1 years; systolic/diastolic blood pressure 132.4+/-12.8/83.3+/-8.1 mm Hg; 13 on antihypertensives). We used 6 batches of North American ginseng root that varied in quality and ginsenoside content, representing the spectrum of this ginseng on the market. On 8 mornings, each participant was fitted with an ambulatory blood pressure monitor, which measured blood pressure during a 30-minute baseline period. Each participant then consumed in a randomized and double-blind fashion 3 g of encapsulated treatment: placebo (on 2 mornings) or powdered North American ginseng (on 6 mornings). After treatment, blood pressure was measured every 10 minutes for 160 minutes, and its change at each post-treatment time point relative to baseline was determined per individual and averaged, and the mean was obtained for the overall 160-minute period. None of the North American ginsengs or their mean differed from placebo in their effect on overall (160 minutes) mean blood pressure change. None affected blood pressure versus placebo at the 10-minute intervals; but their mean versus placebo increased systolic and diastolic blood pressure at 140 and 160 minutes, respectively, and lowered diastolic blood pressure at 100 minutes. The findings together suggested that North American ginseng exerts a neutral acute effect on blood pressure in hypertensive individuals.

  Protective effects of ginseng components in a rodent model of neurodegeneration.:Ann Neurol. 2005 May;57(5):642-8.Lian XY, Zhang Z, Stringer JL.Department of Pharmacology, Baylor College of Medicine, Houston 77030, USA.

 To test the proposed neuroprotective activity of whole ginseng extract and its components, we used 3-nitropropionic acid (3-NP), an inhibitor of succinate dehydrogenase, to produce neurodegeneration. Treatment with 3-nitropropionic acid (90 mg/kg) over a 5-day period resulted in severe impairment of movement and loss of neurons in the striatum. Pretreatment with a preparation from the whole root of American ginseng had no protective effects. Pretreatment with a preparation of ground leaves and stems, which contains greater levels of ginsenosides than ground root, improved the behavioral score and reduced the volume of the striatal lesion. A partial purification of American ginseng was performed to concentrate the putative protective components: Rb1, Rb3, and Rd (termed Rb extract). Pretreatment with the Rb extract significantly reduced the 3-nitropropionic acid-induced motor impairment and cell loss in the striatum, and it completely prevented any mortality. Significant effects on motor function, mortality, and the striatal lesion volume also were measured in animals pretreated with the individual ginsenosides, Rb1, Rb3, or Rd. The results demonstrate that some of the ginsenosides have neuroprotective activity, and that a partial purification of whole ginseng to concentrate the neuroprotective components may have utility as a neuroprotective agent.

  Identification of Panax species in the herbal medicine preparations using gradient PCR method.:Biol Pharm Bull. 2005 Apr;28(4):671-6.Shim YH, Park CD, Kim DH, Cho JH, Cho MH, Kim HJ.College of Pharmacy, Chung Ang University, Seoul, Korea.

 In order to identify the existence of Panax species in herbal medicine preparations, the Ginseng specific marker primer was selected and created based on the sequence of Korean ginseng DNA fragment, 359 bp. The gradient PCR was performed on 40 types of the herbal medicines including the 7 types of Araliaceae that are in the same family with the Panax ginseng using the created Ginseng maker primer. As result, Panax notoginseng (Chinese), Panax japonicus (Japanese) and Panax quinquefolius (American), along with Panax ginseng (Korean) were the only ones amplified. However, in the case of Atractylodes lancea, one of the herbal medicines not categorized as Panax species, the DNA was prominently amplified by the Ginseng marker primer. The sequence of the amplified DNA of Atractylodes lancea was identified, resulting in enabling the differentiation from the Panax species by the Restriction Fragment Length Polymorphisms (RFLP) method. In addition, the results of the gradient PCR performed on the herbal medicine preparations that consists of Panax ginseng showed that 290 bp size of the original DNA fragments of Panax ginseng was amplified on the herbal medicine preparations containing Panax ginseng. Therefore, these results suggest a possibility of creating a new testing method for identifying specific herb medicines using the gradient PCR, a molecular biological method not only on Panax ginseng, but also on other herbal medicines and herbal medicine preparations.


  American ginseng berry extract and ginsenoside Re attenuate cisplatin-induced kaolin intake in rats.:Cancer Chemother Pharmacol. 2005 Jul;56(1):63-9. Epub 2005 Mar 25.Mehendale S, Aung H, Wang A, Yin JJ, Wang CZ, Xie JT, Yuan CS.Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, IL 60637, USA.

 PURPOSE: Cisplatin, a chemotherapeutic agent, causes significant nausea and vomiting. It is postulated that cisplatin-induced oxidant stress may be responsible for these symptoms. We tested whether pretreatment with American ginseng berry extract (AGBE), an herb with potent antioxidant capacity, and one of its active antioxidant constituents, ginsenoside Re, could counter cisplatin-induced emesis using a rat pica model. METHODS: In rats, exposure to emetic stimuli such as cisplatin causes significant kaolin intake, a phenomenon called pica. We therefore measured cisplatin-induced kaolin intake as an indicator of the emetic response. Rats were pretreated with vehicle, AGBE (dose range 50-150 mg/kg, IP) or ginsenoside Re (2 and 5 mg/kg, IP). Rats were treated with cisplatin (3 mg/kg, IP) 30 min later. Kaolin intake, food intake, and body weight were measured every 24 h for 120 h. Additionally, the free radical scavenging activity of AGBE was measured in vitro using ESR spectroscopy. RESULTS: A significant dose-response relationship was observed between increasing doses of pretreatment with AGBE and reduction in cisplatin-induced pica. Kaolin intake was maximally attenuated by AGBE at a dose of 100 mg/kg. Food intake also improved significantly at this dose (P<0.05). Pretreatment with ginsenoside Re (5 mg/kg) also decreased kaolin intake (P<0.05). In vitro studies demonstrated a concentration-response relationship between AGBE and its ability to scavenge superoxide and hydroxyl radicals. CONCLUSION: Pretreatment with AGBE and its major constituent, Re, attenuated cisplatin-induced pica, and demonstrated potential for the treatment of chemotherapy-induced nausea and vomiting. Significant recovery of food intake further strengthens the conclusion that AGBE may exert an antinausea/antiemetic effect.

  Recent trends in use of herbal and other natural products.:Arch Intern Med. 2005 Feb 14;165(3):281-6.Kelly JP, Kaufman DW, Kelley K, Rosenberg L, Anderson TE, Mitchell AA.Slone Epidemiology Center, Boston University School of Public Health, Boston, MA 02215, USA. jkelly@slone.bu.edu

 BACKGROUND: The benefits of herbal and other natural products (dietary supplements) are increasingly cited in the media. Dramatic increases in use reported during the last decade have led to growing concerns about efficacy and safety. METHODS: To determine which dietary supplements American adults use, whether the prevalence has continued to increase in recent years, and whether popularity of individual supplements has changed, demographic information and details of use of all medicines and dietary supplements in the preceding week were obtained by telephone interview from February 1998 through December 2002 from households in 48 contiguous states and the District of Columbia. Participants included randomly selected residents of households with telephones; compared with 2000 US Census data, participants were representative of the US population. The main outcome measure was the weekly prevalence of dietary supplement use, alone or in a multicomponent product. RESULTS: There were 8470 subjects 18 years or older. The annual prevalence of dietary supplement use increased from 14.2% in 1998-1999 to 18.8% in 2002. Although use did not change among younger subjects, it doubled for men and women 65 years or older. Use of Ginkgo biloba and Panax ginseng declined during the study, while lutein use increased dramatically, because of its addition to multivitamin products. The overall 2002 prevalence excluding lutein use was 13.9%. CONCLUSIONS: The popularity of specific supplements has varied over time and differs according to age and sex. The sharp increase in supplement use in the 1990s appears to have slowed. However, the addition of supplements, such as lutein and lycopene, to mainstream multivitamins has become an important source of exposure.

  Modulating angiogenesis: the yin and the yang in ginseng.:Circulation. 2004 Sep 7;110(10):1219-25. Epub 2004 Aug 30.Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW, Yeung HW, Wong RN, Sasisekharan R, Fan TP.Angiogenesis Laboratory, Department of Pharmacology, University of Cambridge, Cambridge, UK. shiladit@MIT.edu

 BACKGROUND: Ginseng is a commonly used nutraceutical. Intriguingly, existing literature reports both wound-healing and antitumor effects of ginseng extract through opposing activities on the vascular system. To elucidate this perplexity, we merged a chemical fingerprinting approach with a deconstructional study of the effects of pure molecules from ginseng extract on angiogenesis. METHODS AND RESULTS: A mass spectrometric compositional analysis of American, Chinese and Korean, and Sanqi ginseng revealed distinct "sterol ginsenoside" fingerprints, especially in the ratio between a triol, Rg1, and a diol, Rb1, the 2 most prevalent constituents. Using a Matrigel implant model and reconstituting the extracts using distinct ratios of the 2 ginsenosides, we demonstrate that the dominance of Rg1 leads to angiogenesis, whereas Rb1 exerts an opposing effect. Rg1 also promoted functional neovascularization into a polymer scaffold in vivo and the proliferation of, chemoinvasion of, and tubulogenesis by endothelial cells in vitro, an effect mediated through the expression of nitric oxide synthase and the phosphatidylinositol-3 kinase-->Akt pathway. In contrast, Rb1 inhibited the earliest step in angiogenesis, the chemoinvasion of endothelial cells. CONCLUSIONS: The present study explains, for the first time, the ambiguity about the effects of ginseng in vascular pathophysiology based on the existence of opposing active principles in the extract. We also unraveled a speciogeographic variation impinging on the compositional fingerprint that may modulate the final phenotype. This emphasizes the need for regulations standardizing herbal therapy, currently under the Dietary Supplement and Health Education Act. Furthermore, we propose that Rg1 could be a prototype for a novel group of nonpeptide molecules that can induce therapeutic angiogenesis, such as in wound healing.

  Ruggedness/robustness evaluation and system suitability test on United States Pharmacopoeia XXVI assay ginsenosides in Asian and American ginseng by high-performance liquid chromatography.:J Pharm Biomed Anal. 2004 Sep 3;35(5):1083-91.Li YG, Chen M, Chou GX, Wang ZT, Hu ZB.Shanghai R&D Center for Standardization of Traditional Chinese Medicines, No 1200 Cai Lun Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China. yongguoli@yahoo.com

 The work of the ruggedness/robustness evaluation and system suitability tests was oriented to profound understand the practicability of using assay methods issued by United States Pharmacopoeia (USP XXVI and XXVII) for ginsenosides in Asian ginseng and American ginseng. The items chosen for the method validation included quantitative related items such as recovery of Rg(1) and Rb(1), respectively, and qualitative related items such as resolution, theoretical plate number, relative retention time of two critical-band-pairs, Rg(1)/Re and Rb(1) with its neighboring peak, respectively. Totally, 16 column types were used for comparison of different vendors, different packing materials, different size, etc. and five sets of LC systems and two laboratories were involved in comparing the data of both quantitative and qualitative items. The results showed that different packing materials of columns used might significantly alters separation. The column packing material Hypersil afforded the preferable separating for the ginsenosides. No significant difference was observed from the different instrumentations and inter-laboratories. Our results suggest a modification of the system suitability test as given in USP26-NF21 and the latest version of USP27-NF22, which was not suitable for most systems. Using resolutions of Rg(1)/Re and Rb(1) with its neighboring peak as critical parameters for the ginsenosides assay and omitting the relative retention time of both Rg(1)/Re and Rb(1) with its neighboring peak is our suggestion for a more reasonable, yet practicable system suitability. Six typical chromatograms gain from different columns were figured out as well.

  Mechanistic studies on protopanaxadiol, Rh2, and ginseng (Panax quinquefolius) extract induced cytotoxicity in intestinal Caco-2 cells.:J Biochem Mol Toxicol. 2004;18(3):143-9.Popovich DG, Kitts DD.Food, Nutrition and Health, Faculty of Agricultural Science, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4.

 Certain ginsenosides, also known as triterpene glycosides, have been recently reported to have a characteristic effect on cultured intestinal and leukemia cell growth. Ginsenoside aglycones 20(S)-protopanaxadiol (PD), 20(S)-protopanaxatriol (PT), and ginsenoside Rh2 have been identified as having a strong effect on reducing cell viability. Furthermore, ginsenoside Rh2 is thought to be a rare ginsenoside not found in all ginseng products. Rather, Rh2 has been recently reported to be a breakdown product of thermal processing of North American ginseng. In this study, pure ginsenosides PD, PT, Rh2 standards and an enriched Rh2 fraction derived from ginseng leaf were tested in cultured Caco-2 cells for relative cytotoxic potency. PD and Rh2 LC50 were similar after 24 to 72 h, whereas a drop in PT LC50 occurred later at 48 and 72 h. Furthermore, PD and Rh2 affected membrane integrity as indicated by LDH secretion earlier than PT and the enriched Rh2 fraction (P < or = 0.05). Ginsenoside Rh2 showed the greatest (P < or = 0.05) build up of necrotic cells (18.3 +/- 0.1%) at the respective LC50 after 24 h and PD (21.3 +/- 0.3%) showed the largest effect after 44 h of exposure. The effect on apoptotic cells at 44 h of treatment were significantly different (P < or = 0.05) for Rh2 (21 +/- 0.4%), PD (14.6 +/- 0.1%), enriched Rh2 leaf fraction (9.9 +/- 0.6%), and PT (2.3 +/- 0.1%) treatments. Caco-2 caspase-3 activity was different between ginsenoside exposure; Rh2 (10.6 +/- 0.3 nM pNA) had the greatest (P < or = 0.05) activity followed by the enriched Rh2 leaf fraction (8.3 +/- 0.2 nM pNA), PT (7.3 +/- 0.3 nM pNA). The PD (4.8 +/- 0.04 nM pNA) treatment was similar to untreated cells (4.3 +/- 0.05 nM pNA) in caspase-3 activity. These results show variable bioactive response in cultured intestinal cell to specific ginsenosides and an enriched Rh2 North American ginseng extract which may be explained on basis of hydrophobic/hydrophilic balance.


  Spatial and genetic structure within populations of wild American ginseng (Panax quinquefolius L., Araliaceae)..:J Hered. 2004 Jul-Aug;95(4):309-21.Cruse-Sanders JM, Hamrick JL.Department of Plant Biology, 2502 Plant Sciences Building, University of Georgia, Athens, GA 30602, USA. jennifer.cruse-sanders@cgu.edu

 Spatial structure and fine-scale genetic structure were analyzed for the medicinal plant American ginseng (Panax quinquefolius L.) to more fully understand biological processes within wild populations. P. quinquefolius has been harvested for more than 250 years and is now considered threatened or rare throughout its range. Plants within four protected and four unprotected populations were significantly clumped based on Ripley's univariate analysis. Analysis with Ripley's bivariate test determined that juvenile plants were significantly clumped with adult plants at the shortest distance classes in all populations. Although plants were highly clumped, we found that significant fine-scale genetic structure was restricted to the shortest distance classes based on estimates of coancestry (f(ij)). In most cases, estimates of f(ij) were more significant among juveniles than among adults, especially at the shortest distance classes. The spatial structure of ginseng seems to result from the establishment and persistence of plants in favorable microhabitats coupled with limited seed dispersal around maternal individuals. There were no differences in patterns of fine-scale genetic structure between protected and unprotected populations.

  Brief communication: American ginseng reduces warfarin's effect in healthy patients: a randomized, controlled Trial.:Ann Intern Med. 2004 Jul 6;141(1):23-7.Yuan CS, Wei G, Dey L, Karrison T, Nahlik L, Maleckar S, Kasza K, Ang-Lee M, Moss J.Tang Center for Herbal Medicine Research, Committee on Clinical Pharmacology and Pharmacogenomics, Anticoagulation Consult Service, Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637, USA. cyuan@uchicago.edu

 BACKGROUND: People using prescription medication often concurrently take herbal supplements. In a case report, the anticoagulant effect of warfarin decreased after patients consumed ginseng. OBJECTIVE: To evaluate the interactions between American ginseng and warfarin. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: General Clinical Research Center, University of Chicago, Chicago, Illinois. PARTICIPANTS: 20 healthy patients. INTERVENTION: In this 4-week study, 20 patients received warfarin for 3 days during weeks 1 and 4. Beginning in week 2, patients were assigned to receive either American ginseng or placebo. MEASUREMENTS: International normalized ratio (INR) and plasma warfarin level. RESULTS: The peak INR statistically significantly decreased after 2 weeks of ginseng administration compared with placebo (difference between ginseng and placebo, -0.19 [95% CI, -0.36 to -0.07]; P = 0.0012). The INR area under the curve (AUC), peak plasma warfarin level, and warfarin AUC were also statistically significantly reduced in the ginseng group as compared with the placebo group. Peak INR and peak plasma warfarin level were positively correlated. LIMITATIONS: The study sample consisted of young, healthy volunteers in a research setting rather than patients taking therapeutic doses of warfarin. CONCLUSIONS: American ginseng reduces warfarin's anticoagulant effect. When prescribing warfarin, physicians should ask patients about ginseng use.

  Decreasing, null and increasing effects of eight popular types of ginseng on acute postprandial glycemic indices in healthy humans: the role of ginsenosides.:J Am Coll Nutr. 2004 Jun;23(3):248-58.Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, ON, Canada.

 BACKGROUND: It is unclear whether other ginseng sources can replicate the glycemic-lowering efficacy observed previously with American ginseng and whether ginsenosides are mediators. We assessed the effect of eight popular ginseng types on postprandial plasma glucose (PG) and insulin (PI) indices, linking effects to ginsenoside profiles. METHODS: Using a double-blind, randomized, multiple-crossover design, 12 healthy participants (gender: 6M:6F, age: 34 +/- 3 y, BMI: 25.8 +/- 1.2 kg/m(2)) received 10 3g treatments: American, American-wild, Asian, Asian-red, Vietnamese-wild, Siberian, Japanese-rhizome, and Sanchi ginsengs and two placebos. Each treatment was given 40-minutes before a 75g-oral-glucose-tolerance-test (75g-OGTT) with blood drawn at -40, 0, 15, 30, 45, 60, 90, 120-minutes. HPLC-UV analysis quantified seven principal ginsenosides. RESULTS: Two-factor analysis showed the main effects of ginseng-type and time were significant for PG and PI, with an interaction for PG (p < 0.05). Subsequent one-factor analysis showed an effect of ginseng-type on 90-min-PG and 90-min-PI (p < 0.05). This was reflected in effects on peak-PG, area under the curve (AUC)-PG and AUC-PI (p < 0.05). But the effect on 90-min-PI and AUC-PI were significant (p < 0.05) only in overweight participants (BMI > 25 kg/m(2), n = 6). Planned comparisons with placebo showed a tendency for American ginseng and Vietnamese ginseng to lower 90-min-PG (p < 0.06), while Asian ginseng raised peak-PG and AUC-PG, American-wild ginseng raised 120-min-PG, and Siberian ginseng raised 90-min-PG, 120-min-PG, and AUC-PG (p < 0.05). Stepwise-multiple-regression assessed the protopanaxadiol:protopanaxatriol (PPD:PPT)-ginsenoside ratio as the sole predictor (p < 0.05) for 90-min-PG (beta = -0.43, r(2) = 0.072), AUC-PG (beta = -0.25, r(2) = 0.06), 90-min-PI (beta = -0.26, r(2) = 0.065), AUC-PI (beta = -0.20, r(2) = 0.04). CONCLUSIONS: Ginseng has variable glycemic effects, in which the PPD:PPT-ginsenoside ratio might be involved. But the low variance explained suggests the involvement of other unmeasured ginsenoside or non-ginsenoside components.

  Effects of different light transmission rate on American ginseng's photosynthesis.:Ying Yong Sheng Tai Xue Bao. 2004 Feb;15(2):261-4. Chinese.Li W, Wan Z, Yang S.Department of Environmental Science, East China Normal University, Shanghai 200062, China. lwlanne@163.com

 From 1997 to 1998, series of experiments were carried out to study American ginseng's photosynthesis related to light transmission rate of plastic cover. The results showed that American ginseng's light saturation point for photosynthesis was different under the different light transmission rate (LTR) because of shading. At about 29.0 degrees C and under 12%, 30%, 42% LTR, 4-year-old American ginseng's light saturation point were 171.0, 323.0, and 429.0 mumol.m-2.s-1, respectively. The maximum net photosynthesis rate (Pn) was 6.54 mg CO2.dm-2.h-1, which appeared under the shading of 30% LTR. The daily course of 3-year-old American ginseng's Pn changed with LTR. When LTR was less than 25.8%, the daily curves of Pn had a single peak, and when LTR was higher than 25.8%, it had two peaks and the leaf's photosynthesis noon break phenomenon was remarkable. The results of single correlative analysis showed that the dominant factor that influenced Pn was photon flux density (PFD), and the results of plural regression analysis showed that the synthetic effect of all the influencing factors together on Pn was significant.

  Anti-hyperglycemic effect of the polysaccharides fraction from American ginseng berry extract in ob/ob mice.:Phytomedicine. 2004 Feb;11(2-3):182-7.Xie JT, Wu JA, Mehendale S, Aung HH, Yuan CS.Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, The University of Chicago, Illinois, USA

 In this study, we evaluated the anti-hyperglycemic effect of a polysaccharides fraction from American ginseng berry extract in diabetic ob/ob mice. All animals received daily intraperitoneal injections of polysaccharides at 150 mg/kg body wt. (n = 5), polysaccharides at 50 mg/kg body wt. (n = 5), or vehicle (n = 5) for 10 consecutive days. On Day 5, as compared to the vehicle-treated mice (230.5 +/- 13.5 mg/dl, mean +/- S.E), mice from both treated groups showed significantly lower fasting blood glucose levels (187.4 +/- 20.5 mg/dl and 187.4 +/- 17.1 mg/dl), respectively (both P < 0.05). On Day 10, compared to the vehicle group (240.1 +/- 12.3 mg/dl), the 50 mg/kg dose group were at 188.4 +/- 12.6 mg/dl (P < 0.05), and the 150 mg/kg dose group were normoglycemic (148.8 +/- 17.6 mg/dl, P < 0.01). Those ob/ob mice treated with vehicle did not, however, show significant changes in fasting blood glucose levels. Data from the intraperitoneal glucose tolerance test (IPGTT) showed that, compared to Day 0, there was a significant improvement in glucose tolerance in animals who received the 50 and 150 mg/kg polysaccharide doses, and the area under the curve (AUC) decreased 15.5% (P < 0.05) and 28.2% (P < 0.01), respectively. Interestingly, after cessation of polysaccharide treatment, the fasting blood glucose levels stayed lower, and returned to control concentration on Day 30. We also observed that the polysaccharides fraction did not affect body weight changes in ob/ob mice. Our data suggest that the polysaccharides fraction from American ginseng berry extract has a potential clinical utility in treating diabetic patients.


  A proprietary extract from North American ginseng (Panax quinquefolium) enhances IL-2 and IFN-gamma productions in murine spleen cells induced by Con-A.:Int Immunopharmacol. 2004 Feb;4(2):311-5.Wang M, Guilbert LJ, Li J, Wu Y, Pang P, Basu TK, Shan JJ.CV Technologies Inc, Edmonton Research Park, Edmonton, AB, Canada T6N 1E5.

 A patented aqueous extract from North American ginseng (Panax quinquefolium), containing mainly oligosaccharides and polysaccharides, is commercially available over the counter as COLD-FX (CVT-E002). This proprietary extract is used for the treatment of upper respiratory tract infections. Its in vitro stimulating effects on the immunoglobulin production by B lymphocytes and on natural immune responses by peritoneal exudates macrophages have been previously reported. Using C57 BL/6 mice, an ex vivo study was conducted to examine Con-A-induced splenocytic productions of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) as markers of acquired immune responses. CVT-E002 (10-500 microg/ml) significantly increased Con-A-induced IL-2 and IFN-gamma productions in spleen cells in a dose-dependent manner. Such response was seen by the ginseng extract originated from three different lots, suggesting consistency between the lots.

  Antioxidant effects of American ginseng berry extract in cardiomyocytes exposed to acute oxidant stress.:Biochim Biophys Acta. 2004 Feb 24;1670(3):165-71.Shao ZH, Xie JT, Vanden Hoek TL, Mehendale S, Aung H, Li CQ, Qin Y, Schumacker PT, Becker LB, Yuan CS.Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, The University of Chicago, IL 60637, USA.

 It is postulated that antioxidant properties of American ginseng root mediate its cardioprotective actions. The antioxidant capabilities of the American ginseng root have been demonstrated previously, however, the berry of the American ginseng has not yet been evaluated. In this study, we tested the American ginseng berry extract (AGBE) for its antioxidant effects in cell-free chemical systems using H(2)O(2)/FeSO(4) to generate hydroxyl radicals which were measured by a fluorescent probe, 2', 7'-dichlorofluorescin diacetate (DCFH/DA). Xanthine/xanthine oxidase was used to generate superoxide anion, which was measured by a fluorescent probe dihydroethidium (DHE). We found that AGBE decreased fluorescence significantly, suggesting that AGBE scavenges oxygen free radicals. We further tested whether AGBE (0.1-1 mg/ml) can protect cardiomyocytes from oxidative injury induced by exogenous or endogenous oxidants. Cells were exposed to either H(2)O(2) or antimycin A (a mitochondrial electron transport chain site III inhibitor that augments mitochondrial oxidant production). The resulting oxidant stress was measured using DCFH/DA and the cell death was assessed using propidium iodide staining. Pretreatment with AGBE (1 mg/ml) significantly attenuated DCF fluorescence by 49% or 85% and reduced cell death by 59% or 63% in cells exposed to H(2)O(2) or antimycin A, respectively. When the effects of extracts from berry and root of American ginseng were compared in cardiomyocytes exposed to antimycin A, we observed that AGBE conferred greater antioxidant protection at the same dose. We conclude that AGBE is a potent antioxidant that protects cardiomyocytes against oxidant-mediated injury and this protection is partly mediated by its free radical scavenging properties.

  Generation of ginsenosides Rg3 and Rh2 from North American ginseng.:Phytochemistry. 2004 Feb;65(3):337-44.Popovich DG, Kitts DD.Food, Nutrition and Health, Faculty of Agricultural Science, University of British Columbia, 6650 NW Marine Drive, Vancouver, BC, Canada V6T 1Z4.

 Rg3 and Rh2 ginsenosides are primarily found in Korean red ginseng root (Panax ginseng C.A. Meyer) and valued for their bioactive properties. We quantified both Rh2 and Rg3 ginseng leaf and Rg3 from root extracts derived from North American ginseng (Panax quinquefolius). Quantification was obtained by application of HPLC with ion fragments detected using ESI-MS. Ginseng leaf contained 11.3+/-0.5 mg/g Rh2 and 7.5+/-0.9 mg/g Rg3 in concentrated extracts compared to 10.6+/-0.4 mg/g Rg3 in ginseng root. No detectable Rh2 was found in root extracts by HPLC, although it was detectable by ESI-MS analysis. Ginsenosides Rg3 and Rh2 were detected following hot water reflux extraction, but not from tissues extracted with 80% aqueous ethanol at room temperature. Therefore ginsenosides Rg3 and Rh2 are not naturally present in North American ginseng, but are products of a thermal process. Using ESI-MS analysis, it was found that formation of Rg3 and Rh2, among other compounds, were a function of heating time and were breakdown products of the more abundant ginsenosides Rb1 and Rc. Our findings that heat processed North American ginseng leaf is an excellent source of Rh2 ginsenoside is an important discovery considering that ginseng leaf material is obtainable throughout the entire plant cycle for recovery of valuable ginsenosides for pharmaceutical use.

  Treatment of menopause-associated vasomotor symptoms: position statement of The North American Menopause Society.:Menopause. 2004 Jan-Feb;11(1):11-33.North American Menopause Society.North American Menopause Society, Cleveland, OH 44101, USA.

 OBJECTIVE: To create an evidence-based position statement regarding the treatment of vasomotor symptoms associated with menopause. DESIGN: The North American Menopause Society (NAMS) enlisted clinicians and researchers acknowledged to be experts in the field of menopause-associated vasomotor symptoms to review the evidence obtained from the medical literature and develop a document for final approval by the NAMS Board of Trustees. RESULTS: For mild hot flashes, lifestyle-related strategies such as keeping the core body temperature cool, participating in regular exercise, and using paced respiration have shown some efficacy without adverse effects. Among nonprescription remedies, clinical trial results are insufficient to either support or refute efficacy for soy foods and isoflavone supplements (from either soy or red clover), black cohosh, or vitamin E; however, no serious side effects have been associated with short-term use of these therapies. Single clinical trials have found no benefit for dong quai, evening primrose oil, ginseng, a Chinese herbal mixture, acupuncture, or magnet therapy. Few data support the efficacy of topical progesterone cream; safety concerns should be the same as for other progestogen preparations. No clinical trials have been conducted on the use of licorice for hot flashes. Among nonhormonal prescription options, the antidepressants venlafaxine, paroxetine, and fluoxetine and the anticonvulsant gabapentin have demonstrated some efficacy for treating hot flashes and were well tolerated. Two antihypertensive agents, clonidine and methyldopa, have shown modest efficacy but with a relatively high rate of adverse effects. For moderate to severe hot flashes, systemic estrogen therapy, either alone (ET) or combined with progestogen (EPT) or in the form of estrogen-progestin oral contraceptives, has been shown to significantly reduce hot flash frequency and severity. Clinical trials have associated ET/EPT with adverse effects, including breast cancer, stroke, and thromboembolism. Several progestogens (both oral and intramuscular formulations) have shown efficacy in treating hot flashes, including women with a history of breast cancer, although no definitive data are available on long-term safety in these women. CONCLUSIONS: In women who need relief for mild vasomotor symptoms, NAMS recommends first considering lifestyle changes, either alone or combined with a nonprescription remedy, such as dietary isoflavones, black cohosh, or vitamin E. Prescription systemic estrogen-containing products remain the therapeutic standard for moderate to severe menopause-related hot flashes. Recommended options for women with concerns or contraindications relating to estrogen-containing treatments include prescription progestogens, venlafaxine, paroxetine, fluoxetine, or gabapentin. Clinicians are advised to enlist women's participation in decision making when weighing the benefits, harms, and scientific uncertainties of therapeutic options. Regardless of the management strategy adopted, treatment should be periodically reassessed as menopause-related vasomotor symptoms will abate over time without any intervention in most women.

  Phytochemistry of wild populations of Panax quinquefolius L. (North American ginseng).:J Agric Food Chem. 2003 Jul 30;51(16):4549-53.Assinewe VA, Baum BR, Gagnon D, Arnason JT.Department of Biology, University of Ottawa, 30 Marie Curie Street, P.O. Box 450, Station A, Ottawa, Ontario K1N 6N5, Canada.

 A survey of the phytochemistry of Panax quinquefolius L. (North American ginseng) collected from wild populations in Ontario, Quebec, Maine, Vermont, and Wisconsin was undertaken. Reverse-phase HPLC was used to determine the natural variation of levels of ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd and their total in leaf, stem, and root of authentic wild-grown material. The totals in roots varied from 1 to 16%, with the greatest number of individual samples having 4-5% total ginsenosides. The lack of ginsenoside Rf in roots of authentic wild populations confirmed its status as a phytochemical marker differentiating American and Asian ginseng. Ten geographically isolated wild populations were collected, and several showed significant variation in the levels of major ginsenosides. There was no statistical difference in mean ginsenoside content between wild and cultivated P. quinquefolius roots at 4 years of age, suggesting there is no phytochemical justification for wild crafting. Baseline data on total ginsenoside levels for authentic wild P. quinquefolius reported here provide reference levels for quality assurance programs.


  A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults.:J Am Geriatr Soc. 2004 Jan;52(1):13-9. Erratum in: J Am Geriatr Soc. 2004 May;52(5):following 856.McElhaney JE, Gravenstein S, Cole SK, Davidson E, O'neill D, Petitjean S, Rumble B, Shan JJ.Eastern Virginia Medical School, Norfolk, Virginia, USA. jmcelhaney@uchc.edu

 OBJECTIVES: To compare a proprietary extract of American ginseng, CVT-E002, with placebo in preventing acute respiratory illness (ARI) in an institutional setting during the influenza season. DESIGN: Two randomized, double-blind, placebo-controlled trials conducted late in the 2000 (8 week) and 2000-2001 (12 week) influenza seasons. SETTING: Long-term care setting that included nursing home and assisted living at three sites. PARTICIPANTS: Eighty-nine (2000) and 109 (2000-2001) enrolled subjects, average age 81 and 83.5, respectively; 74% women. Approximately 90% had received influenza vaccine in each of the 2 years. INTERVENTION: Oral twice-daily administration of a proprietary ginseng extract, CVT-E002, 200 mg or placebo. MEASUREMENTS: ARI was defined as two new respiratory symptoms or one with a constitutional symptom. Confirmation of viral ARI was by culture (influenza or respiratory syncytial virus (RSV)) or serology for influenza. Laboratory safety monitoring was done at 0, 4, and 8 or 12 weeks. RESULTS: An intent-to-treat analysis of pooled data corrected for drug exposure time showed that the incidence of laboratory-confirmed influenza illness (LCII) was greater in placebo- (7 cases/101 subjects) than CVT-E002-treated (1/97) groups (odds ratio (OR)=7.73, P=.033). Combined data for LCII and RSV illness were also greater in placebo- (9/101) than CVT-E002-treated (1/97) groups (OR=10.50, P=.009), for an overall 89% relative risk reduction of ARI in the CVT-E002 group. CONCLUSION: CVT-E002 was shown to be safe, well tolerated, and potentially effective for preventing ARI due to influenza and RSV.

  American ginseng leaf: ginsenoside analysis and hypoglycemic activity.:Pharmacol Res. 2004 Feb;49(2):113-7.Xie JT, Mehendale SR, Wang A, Han AH, Wu JA, Osinski J, Yuan CS.Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 4028, Chicago, IL 60637, USA.

 Previous studies showed that both American ginseng root and American ginseng berry extracts possess hypoglycemic properties. In this study, we investigated whether American ginseng leaves also have similar capabilities. We first analyzed the chemical constituents of American ginseng leaf and determined the content of six major ginsenosides, i.e., Rb(1), Rb(2), Rc, Rd, Re, and Rg(1), by high performance liquid chromatography (HPLC). Subsequently, we evaluated the hypoglycemic effect of American ginseng leaf extract (AGLE) in diabetic ob/ob adult mice. Animals received daily intraperitoneal injections of AGLE 50, 150 mg/kg or vehicle for 12 consecutive days. Fasting blood glucose levels, intraperitoneal glucose tolerance test (IPGTT), body weight and temperature were measured. On day 5, the 150 mg/kg AGLE group had significantly lower fasting blood glucose levels compared to vehicle-treated mice (223.0+/-13.9 mg/dl versus 258.0+/-14.0 mg/dl, P<0.05), while the blood glucose levels in 50 mg/kg group did not decrease significantly. On day 12, the glucose levels in both AGLE-treated groups were reduced significantly compared to vehicle group (180.0+/-10.0 mg/dl and 220.2+/-19.3 versus 268.0+/-10.0 mg/dl, P<0.01 and <0.05, respectively). IPGTT data showed that both AGLE 150 and 50 mg/kg groups significantly increased the glucose disposal on day 12 compared to the vehicle group. In addition, body weight decreased in ob/ob mice after AGLE treatment, and these body weight changes were accompanied by significant increases in body temperature (P<0.05). Our results suggest that AGLE possesses a significant anti-hyperglycemic and thermogenic activity and may prove to be beneficial in improving the management of type 2 diabetes.

  Chronic ginseng consumption attenuates age-associated oxidative stress in rats.:J Nutr. 2003 Nov;133(11):3603-9.Fu Y, Ji LL.Department of Kinesiology and Nutritional Science, University of Wisconsin-Madison, Madison, WI 53706, USA.

 The antioxidant properties of North American ginseng (Panax quinquefolium) were investigated in young and old rats fed a ginseng-supplemented diet for 4 mo. Female Fischer 344 rats at 4 (Y, n = 38) or 22 (O, n = 25) mo of age were randomly divided into three groups and fed either a AIN-93G formula-based control diet (C) or a diet containing 0.5 g/kg (low dose, L) or 2.5 g/kg (high dose, H) dry ginseng power for 4 mo. Oxidant generation, measured with 2'7'-dichlorofluorescin (DCFH), was significantly lowered with ginseng feeding in the homogenates of heart, soleus, and the deep portion of vastus lateralis muscle (DVL) (P < 0.05) in both Y and O rats, and the effects were dose dependent. Superoxide dismutase activity was elevated in heart and DVL of H rats, and in soleus of L rats (P < 0.05). H rats showed higher glutathione peroxidase activity in DVL and soleus muscle (P < 0.05), and elevated citrate synthase activity in the heart of both age groups and DVL of Y rats (P < 0.05). Neither the H nor L diet affected age-dependent lipid peroxidation in the heart or muscle, but protein carbonyl content was attenuated with the H diet in the heart (P < 0.05) and with both the L and H diets in DVL (P < 0.01). We conclude that ginseng supplementation can prevent age-associated increase in oxidant production and oxidative protein damage in rats. These protective effects are explained in part by elevated antioxidant enzyme activities in the various tissues.

  Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice.:Pharmacol Biochem Behav. 2003 Aug;76(1):103-9.Wu CF, Liu YL, Song M, Liu W, Wang JH, Li X, Yang JY.Department of Pharmacology, Shenyang Pharmaceutical University, Wenhua Road 103, 110016 Shenyang, People's Republic of China. wuchunf@21cn.com

 In the present study, pseudoginsenoside-F(11) (PF(11)), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF(11) was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF(11) did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF(11) significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF(11) greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF(11) significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF(11) could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF(11) is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

  Genetic authentication of ginseng and other traditional Chinese medicine.:Acta Pharmacol Sin. 2003 Sep;24(9):841-6. Review.Hon CC, Chow YC, Zeng FY, Leung FC.Department of Zoology, The University of Hong Kong, Hong Kong SAR, China.

 The main objective of this paper is to review the chemical and genetic methods used in authentication of ginseng, especially the recent advances in microsatellite genotyping and its application to the authentication of other traditional Chinese medicines (TCM). The standardization and modernization of TCM hinge on the authentication of their botanical identities. Analysis of well-characterized marker compounds is now the most popular method for identifying the herbal materials and quality control of TCM, eg, ginsenoside profiling for authentication of Panax species. However, in many herbal species the chemical composition of the plant changes with the external environment and processing conditions, which lowers the reliability of these authentication methods. In the light of the advances in molecular biotechnology in the past few decades, genetic tools are now considered to provide more standardized and reliable methods for authentication of herbal materials at the DNA level. These genetic tools include random amplified polymorphic DNA (RAPD), DNA fingerprinting using multi-loci probes, restriction fragment length polymorphism (RFLP), amplified fragment length polymorphism (AFLP), and microsatellite marker technology. The practicality of these methods varies in terms of their sensitivity, reliability, reproducibility, and running cost. Using ginseng as an example, we reviewed the advantages and limitations of these molecular techniques in TCM authentication. We have developed a set of microsatellite markers from American ginseng that are able to differentiate Panax ginseng and Panax quinquetolius with the resolution down to farm level, ie, confirmation of its botanical identity and origin. Compared with other molecular techniques, microsatellite marker technology is more robust, accurate, reproducible, reliable, and sensitive. This is essential for large-scale TCM authentication centers.


  Ginsenosides stimulate the growth of soilborne pathogens of American ginseng.:Phytochemistry. 2003 Sep;64(1):257-64.Nicol RW, Yousef L, Traquair JA, Bernards MA.Department of Biology, University of Western Ontario, London, ON, Canada N6A 5B7.

 Ginseng saponins (ginsenosides) were isolated from soil associated with the roots of commercially grown American ginseng (Panax quinquefolius L.), identified via LC-MS and quantified via analytical HPLC. The ginsenosides, including F(11), Rb(1), Rb(2), Rc, Rd, Re and Rg(1), represented between 0.02 and 0.098% (average 0.06%) of the mass of the soil collected from roots annually between 1999 and 2002. The same ginsenosides were also isolated from run-off of undisturbed plants grown in pots in a greenhouse using a root exudate trapping system. To investigate (1) whether these saponins could influence the growth of pythiaceous fungi pathogenic to ginseng, and (2) whether soil levels of ginsenosides were sufficient to account for any effects, bioassays were completed using a crude saponin extract and an ecologically relevant concentration of purified ginsenosides. Thus, when cultured on media containing crude saponins, the colony weight of both Phytophthora cactorum and Pythium irregulare was significantly greater than that of control, indicating a strong growth stimulation by ginsenosides. The growth of Pythium irregulare was also significantly stimulated after addition of an ecologically relevant, low concentration (i.e. 0.06%) of purified ginsenosides to culture medium. By contrast, growth of the saprotrophic fungus Trichoderma hamatum was slightly (but not significantly) inhibited under the same conditions. These results imply that ginsenosides can act as allelopathic stimulators of the growth of pythiaceous fungi in the rhizosphere, and this may contribute to the disease(s) of this crop.

  A rapid method for detecting seven kinds of American ginseng tea bags by FTIR spectroscopy.:Guang Pu Xue Yu Guang Pu Fen Xi. 2002 Aug;22(4):600-2. Sun SQ, Zhou Q, Leung HW, Yeung HW.Department of Chemistry, Tsinghua University, Beijing 100084, China.Chinese.

 A rapid and non-destructive method, was used to identify seven commercial American Ginseng Tea bags by Fourier-transform infrared spectroscopy (FTIR) in this paper. It could be seen from the results, that each sample has its own characteristic infrared spectrum. Also, the seven tea bags could be divided into two groups: one is made from pure Ginseng powders, and the other is made by Ginseng extractives and additives. The information of additives used by factories could be identified by IR spectra. For example, some factories use glucose, and the others use sucrose as the additives. Furthermore, the quality of the tea bags was identified by the intensity ratio of Ginsengs and additives. In HPLC, the total saponin in tea bags made from Ginseng powders is 4 times higher than that made by Ginseng extractives. Therefore, HPLC analysis gave the same result with FTIR. It is proved that FTIR is a very fast, simple and reliable method to identify Chinese medicine.

  Understory light and root ginsenosides in forest-grown Panax quinquefolius.:Phytochemistry. 2003 Aug;63(7):777-82.Fournier AR, Proctor JT, Gauthier L, Khanizadeh S, B¨¦langer A, Gosselin A, Dorais M.Horticultural Research Centre, Envirotron Building, Laval University, Quebec, Canada G1K 7P4

 The objective of this study was to determine the relationship between light levels in the understory of a broadleaf forest and the content of six ginsenosides (Rg(1), Re, Rb(1), Rc, Rb(2,) and Rd) in 1- and 2-year-old American ginseng (Panax quinquefolius L.) roots. Our results revealed that ginsenoside contents in 1- and 2 year-old roots collected in September were significantly related to direct and total light levels, and duration of sunflecks. At this time, the effect of light levels accounted for up to 48 and 62% of the variation in ginsenoside contents of 1- and 2-year-old American ginseng roots. Also, red (R) and far red (FR) light, and the R:FR ratio significantly affected Rd, Rc, and Rg(1) contents in 2-year-old roots, accounting for up to 40% of the variation in ginsenoside contents.

  Herbs commonly used by women: an evidence-based review.:Am J Obstet Gynecol. 2003 May;188(5 Suppl):S44-55. Review.Tesch BJ.Division of General Internal Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.

 OBJECTIVE: To review the evidence of herbs commonly used by women. DATA SOURCES: Articles were located by searching Medline, Cochrane Database of Systemic Reviews, and the Combined Health Information Database and by hand searching the reference lists of recent systematic reviews. The databases were searched in January 2000 and October 2000 by using the Latin and common name of each herb. METHODS OF STUDY SELECTION: Preference was given to randomized, placebo-controlled trials. When available, English language studies were reviewed. If not, data are presented from review articles that summarize the foreign study. RESULTS: Many women use herbal therapies. In the United States, herbs are considered dietary supplements. The Food and Drug Administration (FDA) cannot remove them from the market unless they are proven unsafe. The herb industry plans to improve monitoring. Many prospective randomized controlled trials are being funded. Gingko biloba seems to slow the progression of dementia but increases the risk of bleeding. St John's Wort is efficacious for treating mild to moderate depression but has many drug interactions. Ginseng seems to improve well being in perimenopausal women, but it is often impure and has side effects and drug interactions. Garlic slightly lowers blood pressure and lipids. Echinacea slightly decreases the duration of colds but does not prevent them. Valerian is beneficial for insomnia, but there is no long-term safety data. Black cohosh may help the symptoms of perimenopause, and chasteberry may improve premenstrual syndrome. More study is needed on both herbs. CONCLUSION: Some herbs are medically useful, but the American public would benefit from increased regulation. Manufacturers should be able to ensure that herbs contain pure ingredients. Side effects and drug interactions should be listed. Well-designed studies are being conducted. The results will be helpful to physicians and patients when the clinical evidence becomes available.

  Systematic review of herbs and dietary supplements for glycemic control in diabetes.:Diabetes Care. 2003 Apr;26(4):1277-94. Review.Yeh GY, Eisenberg DM, Kaptchuk TJ, Phillips RS.Division for Research and Education in Complementary and Integrative Medical Therapies, Harvard Medical School, Boston, Massachusetts, USA. gyeh@caregroup.harvard.edu

 OBJECTIVE: To conduct a systematic review of the published literature on the efficacy and safety of herbal therapies and vitamin/mineral supplements for glucose control in patients with diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic literature search of MEDLINE, OLDMEDLINE, Cochrane Library Database, and HealthSTAR, from database inception to May 2002, in addition to performing hand searches and consulting with experts in the field. Available clinical studies published in the English language that used human participants and examined glycemic control were included. Data were extracted in a standardized manner, and two independent investigators assessed methodological quality of randomized controlled trials using the Jadad scale. RESULTS: A total of 108 trials examining 36 herbs (single or in combination) and 9 vitamin/mineral supplements, involving 4,565 patients with diabetes or impaired glucose tolerance, met the inclusion criteria and were analyzed. There were 58 controlled clinical trials involving individuals with diabetes or impaired glucose tolerance (42 randomized and 16 nonrandomized trials). Most studies involved patients with type 2 diabetes. Heterogeneity and the small number of studies per supplement precluded formal meta-analyses. Of these 58 trials, the direction of the evidence for improved glucose control was positive in 76% (44 of 58). Very few adverse effects were reported. CONCLUSIONS: There is still insufficient evidence to draw definitive conclusions about the efficacy of individual herbs and supplements for diabetes; however, they appear to be generally safe. The available data suggest that several supplements may warrant further study. The best evidence for efficacy from adequately designed randomized controlled trials (RCTs) is available for Coccinia indica and American ginseng. Chromium has been the most widely studied supplement. Other supplements with positive preliminary results include Gymnema sylvestre, Aloe vera, vanadium, Momordica charantia, and nopal.


  Biological effects of supplements on soil properties and the growth of Panax quinquefolium.:Zhong Yao Cai. 2000 Apr;23(4):187-8. Chinese.Liu H, Hu B, Zhao Y, Song J, Zhang G, Fu J, Liu W.Institute of Medicinal Plants, Chinese Academy of Medical Scienses/Peking Union Medical University, Beijing 100094.

 This paper suggests that the physical and chemical characteristics of soil in American ginseng field were greatly improved after utilization of supplement on soil. Compared with the contrast, the soil gravity ratio decreased from 0.812 g/cm3 to 0.715 g/cm3, while the soil porosity increased from 69.36% to 73.03%. These improvements are benefit for the growth of Panax quinquefolium. Biological observations show that the fresh weight of ginseng root enhanced 53.8%, and the content of total saponins in root enhanced 0.5%-1% (get to 8.28%).

  Herbal preparations have both effects and side effects. Widespread usage dictates knowledge among physicians.:Lakartidningen. 2002 Dec 12;99(50):5095-7. Swedish.Mattsson K, Nilsson I.karin.mattsson@apoteket.se

 The article gives a clinically oriented overview of the efficacy and safety of Ginkgo biloba, St. John's wort, ginseng, Echinacea, saw palmetto and kava based on American experiences. Clinical data support the efficacy for some of these drugs. None of them is free of adverse effects. Generally speaking, trials of herbal medicinal products have been too few, too small and too short. The lack of long-term studies is especially unfortunate since many of the drugs are used for a long time. The difference between American and Swedish legislation on herbal medicine products is described.

  Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.) with a depressed ginsenoside profile does not affect postprandial glycemia.:Eur J Clin Nutr. 2003 Feb;57(2):243-8.Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

 BACKGROUND: We have repeatedly reported that American ginseng (AG) with a specific ginsenoside profile significantly decreases postprandial glycemia. Whether this effect is reproducible using AG with a different profile is unknown. We therefore investigated the effect of a different batch of AG on glycemia following a 75 g oral glucose tolerance test (OGTT). METHODS: Using a randomized, single blind design, 12 normal subjects (six males and six females, aged 31+/-3 y, body mass index (BMI) 28+/-2 kg/m(2)) received 6 g AG or placebo 40 min before a 75 g OGTT. The protocol followed the guidelines for the OGTT, with venous blood samples drawn at -40, 0, 15, 30, 45, 60, 90 and 120 min. Ginsenosides in the AG were assessed by established methods for HPLC-UV. RESULTS: Repeated measures analysis of variance demonstrated that there was no significant effect of the AG on incremental plasma glucose (PG) or insulin (PI) or their areas under the curve Indices of insulin sensitivity (insulin sensitivity index (ISI)) and release (deltaPI(30-0)/deltaPG(30-0)) calculated from the OGTT were also unaffected. The AG contained 1.66% total ginsenosides, 0.90% (20S)-protopanaxadiol (PPD) ginsenosides, and 0.75% (20S)-protopanaxatriol (PPT) ginsenosides, with the following key ratios: PPD:PPT of 1.2, Rb(1):Rg(1) of 8.1, and Rb(2):Rc of 0.18. CONCLUSIONS: The present batch of AG was unable to reproduce the postprandial hypoglycemic effects we observed previously. Possible explanations for this discrepancy include marked decrements in total ginsenosides and the key ratios PPD:PPT, Rb(1):Rg(1), and Rb(2):Rc. These data suggest that the ginsenoside profile of AG might play a role in its hypoglycemic effects. The involvement of other components cannot, however, be precluded.

  Pressurized liquid extraction of active ingredients (ginsenosides) from medicinal plants using non-ionic surfactant solutions.:J Chromatogr A. 2003 Jan 3;983(1-2):153-62.Choi MP, Chan KK, Leung HW, Huie CW.Department of Chemistry, Hong Kong Baptist University, 224 Waterloo Road, Kowloon Tong, Hong Kong.

 The feasibility of employing aqueous non-ionic surfactant solutions as an alternative solvent system in pressurized liquid extraction (PLE) is demonstrated for the first time using the roots of American ginseng as model solid samples. When compared to the use of pure water or methanol, the presence of a common non-ionic surfactant (Triton X-100) in water at a concentration above its critical micelle concentration was shown to enhance the amount of pharmacologically active ingredients (ginsenosides) extracted from ginseng roots. The advantages of using aqueous non-surfactant solutions were also demonstrated by comparing extraction performances between ultrasonic-assisted extraction and PLE methods. Furthermore, the combination of PLE and cloud point extraction was shown to be a new and effective approach for the rapid sample preconcentration of herbal materials prior to analysis by high-performance liquid chromatography.

  Herbs commonly used by women: an evidence-based review.:Dis Mon. 2002 Oct;48(10):671-96. Review.Tesch BJ.

 OBJECTIVE: To review the evidence of herbs commonly used by women. DATA SOURCES: Articles were located by searching Medline, Cochrane Database of Systemic Reviews, and the Combined Health Information Database and by hand searching the reference lists of recent systematic reviews. The databases were searched in January 2000 and October 2000 by using the Latin and common name of each herb. METHODS OF STUDY SELECTION: Preference was given to randomized, placebo-controlled trials. When available, English language studies were reviewed. If not, data are presented from review articles that summarize the foreign study. RESULTS: Many women use herbal therapies. In the United States, herbs are considered dietary supplements. The Food and Drug Administration (FDA) cannot remove them from the market unless they are proven unsafe. The herb industry plans to improve monitoring. Many prospective randomized controlled trials are being funded. Gingko biloba seems to slow the progression of dementia but increases the risk of bleeding. St John's Wort is efficacious for treating mild to moderate depression but has many drug interactions. Ginseng seems to improve well being in perimenopausal women, but it is often impure and has side effects and drug interactions. Garlic slightly lowers blood pressure and lipids. Echinacea slightly decreases the duration of colds but does not prevent them. Valerian is beneficial for insomnia, but there is no long-term safety data. Black cohosh may help the symptoms of perimenopause, and chasteberry may improve premenstrual syndrome. More study is needed on both herbs. CONCLUSION: Some herbs are medically useful, but the American public would benefit from increased regulation. Manufacturers should be able to ensure that herbs contain pure ingredients. Side effects and drug interactions should be listed. Well-designed studies are being conducted. The results will be helpful to physicians and patients when the clinical evidence becomes available.


  Botanical dietary supplement use in peri- and postmenopausal women.:Menopause. 2003 Jan-Feb;10(1):65-72.Mahady GB, Parrot J, Lee C, Yun GS, Dan A. University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research, Department of Pharmacy Practice, Center for Excellence in Women's Health, Chicago, Illinois, USA. mahady@uic.edu

 OBJECTIVE: To determine use of botanical dietary supplements (BDS) in women between the ages of 40 and 60 years at the University of Illinois at Chicago (UIC) clinics, including information about commonly used BDS, the reason for use, information resources used, and the overall perception of safety and efficacy of BDS. DESIGN: Five hundred female outpatients at UIC clinics were interviewed by healthcare practitioners using a botanical/drug history questionnaire. Respondents were 46.8% African American, 39.6% Caucasian, 11.7% Hispanic, and 1.5% Asian, with a mean age of 50.34 years. RESULTS: BDS were used by 79% of respondents ( = 395), of which 36.5% used BDS daily. Of the positive respondents, 51.7% used one or two BDS, whereas 48.4% used three or more. Commonly used botanicals included soy (42%), green tea (34.68%), chamomile (20.76%), gingko (20.51%), ginseng (17.97%), Echinacea (15.44%), and St. John's wort (7.34%). Black cohosh, garlic, red clover, kava, valerian, evening primrose, and ephedra were used by less than 15% of respondents. Efficacy ratings were high for BDS, and 68% claimed to have no side effects. Only 3% of respondents obtained BDS information from healthcare professionals, and 70% of respondents were not informing their physician of BDS use. CONCLUSIONS: A high percentage of women at UIC clinics were using multiple BDS. The respondents believed that these products were both safe and effective for the treatment of common ailments. Concomitant BDS use with prescription and over-the-counter medications was commonplace, often without a physician's knowledge. Consumer education about the possible benefits and risks associated with BDS use is urgently needed.

  Liquid chromatography/mass spectrometry of malonyl-ginsenosides in the authentication of ginseng.:Rapid Commun Mass Spectrom. 2003;17(3):238-44.Kite GC, Howes MJ, Leon CJ, Simmonds MS.Royal Botanic Gardens, Kew, Richmond, Surrey TW9 3AB, UK.

 Different negative ion electrospray (ES) source conditions are required to concentrate the ion current in [M-H](-) for malonylated and non-malonylated ginsenosides. However, both can be ionised optimally in a single liquid chromatography/mass spectrometry (LC/MS) analysis by employing switchable voltages in the post-source ion optics of a quadrupole ion trap mass spectrometer. Coupled with automatic MS/MS scanning and post-acquisition neutral loss data analysis, this method provides a means of profiling the malonylated and acetylated ginsenosides in ginseng extracts. Analyses revealed numerous malonylated ginsenosides that could be partially characterised by serial MS/MS experiments. The ratio of mRb(1) to other isomeric forms present and to mRb(2) and mRc appears to show consistent differences among Panax ginseng (Asian ginseng), P. quinquefolius (American ginseng) and P. notoginseng (Sanchi ginseng). The ratio of malonylated to non-malonylated ginsenosides is reduced in the red form of Asian ginseng compared with the white form and there is a concomitant increase in the levels of the corresponding acetylated ginsenosides. The ability to analyse malonylated ginsenosides is an important contribution to the range of chemical characteristics that can be used to authenticate the different species of ginseng and will assist in quality control and standardisation.

  Peripheral blood mononuclear cell production of TNF-alpha in response to North American ginseng stimulation.:Can J Physiol Pharmacol. 2002 Oct;80(10):1030-3.Zhou DL, Kitts DD.Food, Nutrition, and Health, Faculty of Agricultural Science, University of British Columbia, 6650 NW Marine Drive, Vancouver, BC V6T 1Z4, Canada.

 North American ginseng (Panax quinquefolium) root extract (NAGE) with known ginsenosides composition was examined for its affinity to stimulate human tumour necrosis factor alpha (TNF-alpha) production in human peripheral blood mononuclear cells. Case studies were conducted in three donors, one that was diagnosed with an atopic allergy and two that were normal, healthy subjects. Cultured mononuclear cells were incubated with varying concentrations of NAGE for up to 72 h and culture media were tested for TNF-alpha concentration. Direct stimulation of mononuclear cell TNF-alpha production in vitro by NAGE occurred as early as 6 h with 200 microg NAGE/mL. The stimulation of TNF-alpha production was confirmed by TNF-alpha mRNA gene expression. These interesting results show the immunostimulating activity of NAGE components in reference to TNF-alpha production. This observation requires further investigation with more subjects to determine the affinity of ginseng in stimulating the human immune system. Moreover, the method of evaluating this response is very useful for standardizing ginseng extracts to a known bioactivity.

  Decreased Hill reaction rates and slow turnover of transitory starch in the obligate shade plant Panax quinquefolius L. (American ginseng).:Planta. 2002 Oct;215(6):969-79. Epub 2002 Aug 21.Miskell JA, Parmenter G, Eaton-Rye JJ.Biochemistry Department, University of Otago, P.O. Box 56, Dunedin, New Zealand.

 To identify physiological processes that might limit photosynthesis in Panax quinquefolius L. (American ginseng) a comparison has been made with Panax ginseng C.A. Meyer (Korean ginseng), Pisum sativum L. (pea) and Spinacia oleracea L. (spinach). The quantum yield of oxygen evolution in intact leaves and isolated thylakoid membranes was found to be smaller in ginseng than in pea or spinach. However, the number of photosystem II (PSII) centers on a chlorophyll basis was found to be similar in all species. This suggests that ginseng thylakoid membranes possess relatively more inactive PSII centers than thylakoids of pea and spinach when grown under similar conditions. Unexpectedly, whole-chain electron transport from water to methyl viologen, and partial photosystem I reactions, demonstrated that electron transport rates to methyl viologen were anomalously low in P. quinquefolius and P. ginseng. Additionally, at elevated light intensities, intact leaves of P. quinquefolius were more susceptible to lipid peroxidation than pea leaves. In plants grown at a light intensity of 80 micro mol photons m(-2) s(-1) the levels of fructose and starch were higher in both ginseng species than in pea or spinach. Significantly, the level of starch in P. quinquefolius was relatively constant throughout the entire 12 h/12 h light/dark cycle and remained high after an extended dark time of 48 h. In addition, P. quinquefolius had lower activities of alpha-amylase and beta-amylase than P. ginseng, pea and Arabidopsis thaliana (L.) Heynh. The significance of the elevated levels of leaf starch in P. quinquefolius remains to be determined. However, the susceptibility of P. quinquefolius to photoinhibition may arise as a consequence of a reduced fraction of active PSII centers. This may result in the normal dissipative mechanisms in these plants becoming saturated at elevated, but moderate, light intensities.

  Effects of American ginseng berry extract on blood glucose levels in ob/ob mice.:Am J Chin Med. 2002;30(2-3):187-94.Xie JT, Aung HH, Wu JA, Attel AS, Yuan CS.Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, Illinois 60637, USA.

 In this study, we evaluated antihyperglycemic effects of American ginseng berry extract in diabetic ob/ob mice. Animals received daily intraperitoneal (IP) injections of the extract 150 mg/kg for 12 days. On days 5 and 12, the extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to day 0 (both p < 0.05). Glucose tolerance improved significantly, which was shown by overall glucose excursion, calculated as area under the curve (AUC) during the two-hour IP glucose tolerance test. The AUC decreased by 31.8% on day 12 compared to day 0 (p < 0.01). In addition, after 12 days of the berry extract treatment, a significant reduction in body weight (p < 0.01 compared to day 0) and a significant increase in body temperature (p < 0.01 compared to day 0) was noticeable. Our results support in vivo antihyperglycemic and antiobese activity of American ginseng berry extract that may prove to be of clinical importance in the prevention and treatment of Type 2 diabetes.


  Extractable polysaccharides of Panax quinquefolius L. (North American ginseng) root stimulate TNFalpha production by alveolar macrophages.:Phytomedicine. 2002 Jul;9(5):398-404.Assinewe VA, Amason JT, Aubry A, Mullin J, Lemaire I.Department of Biology, University of Ottawa, Canada.

 We have investigated the immunostimulatory activity of the medicinal plant Panax quinquefolius L. (North American ginseng). Rat alveolar macrophages were treated with different extracts from 4-year old roots, and tumour necrosis factor alpha (TNF) production was used as a measure of immunostimulatory activity. Aqueous extracts of P. quinquefolius root (1-100 microg/ml) were found to significantly stimulate alveolar macrophage TNF release. Both a P. quinquefolius methanol extract containing ginsenosides (but no polysaccharides), and pure ginsenoside-Rb1, the major ginsenoside present in P. quinquefolius, were found to be inactive as TNF-stimulating agents. Significant TNF-stimulating activity was found in the extractable polysaccharide fraction, which was hydrolyzed and found to contain glucose, galactose, arabinose, rhamnose, and mannose. This represents the first evidence that North American ginseng exerts cytokine-stimulating activity on macrophages.

  Ginseng, sex behavior, and nitric oxide.:Ann N Y Acad Sci. 2002 May;962:372-7. Review.Murphy LL, Lee TJ.Department of Physiology, Southern Illinois University, School of Medicine, Carbondale, Illinois 62901, USA. lmurphy@siumed.edu

 In Asia, ginseng is commonly included in herbals used for the treatment of sexual dysfunction. Recent studies in laboratory animals have shown that both Asian and American forms of ginseng enhance libido and copulatory performance. These effects of ginseng may not be due to changes in hormone secretion, but to direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissues. Indeed, there is good evidence that ginsenosides can facilitate penile erection by directly inducing the vasodilatation and relaxation of penile corpus cavernosum. Moreover, the effects of ginseng on the corpus cavernosum appear to be mediated by the release and/or modification of release of nitric oxide from endothelial cells and perivascular nerves. Treatment with American ginseng also affects the central nervous system and has been shown to significantly alter the activity of hypothalamic catecholamines involved in the facilitation of copulatory behavior and hormone secretion. Recent findings that ginseng treatment decreased prolactin secretion also suggested a direct nitric oxide-mediated effect of ginseng at the level of the anterior pituitary. Thus, animal studies lend growing support for the use of ginseng in the treatment of sexual dysfunction and provide increasing evidence for a role of nitric oxide in the mechanism of ginsenoside action.

  Use of alternative pharmacotherapy in management of cardiovascular diseases.:Am J Manag Care. 2002 Mar;8(3):270-85; quiz 286-8. Review.Chagan L, Ioselovich A, Asherova L, Cheng JW.Shore Health System, Easton, MD, USA.

 OBJECTIVES: To review use of alternative pharmacotherapy (AP) in patients with cardiovascular disease (CVD) and significant drug interactions between AP and traditional CVD medications. STUDY DESIGN: A literature search of MEDLINE and the National Complementary and Alternative Medicine database was done using these search terms: supplements, vitamins, garlic, fish oil, L-arginine, soy, coenzyme Q10, herbs, phytosterols, chelation therapy, alternative medicine, and CVD. PATIENTS AND METHODS: English human clinical trials measuring surrogate and clinical end points. RESULTS: Antioxidants have not been consistently proven beneficial in reducing cardiovascular mortality. Fish oils may be beneficial in patients with hypertension and hypercholesterolemia, but therapeutic doses need to be defined. Use of coenzyme Q10 in patients with heart failure has not demonstrated consistent benefits. Garlic may lower blood pressure and cholesterol levels, but also may increase bleeding, so its use in CVD patients should be monitored. Clinical studies with small sample sizes have demonstrated that L-arginine may be useful to prevent and treat CVD. The Food and Drug Administration recommends 25 g/day of soy protein as part of a diet low in saturated fats for cholesterol reduction. Plant sterols are recommended by the American Heart Association and the National Cholesterol Education Program Expert Panel as adjunct therapy to reduce low-density lipoprotein. No data support use of chelation therapy. Some APs interact with common prescription CVD medications (eg, gingko and ginseng with warfarin, St. John's Wort with digoxin). CONCLUSIONS: The benefits of APs as part of the treatment for CVD are controversial. Routine use is not recommended.

  In vitro effect of standardized ginseng extracts and individual ginsenosides on the catalytic activity of human CYP1A1, CYP1A2, and CYP1B1.:Drug Metab Dispos. 2002 Apr;30(4):378-84.Chang TK, Chen J, Benetton SA.Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada. tchang@unixg.ubc.ca

 Ginseng extract has been reported to decrease the incidence of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated tumorigenesis in mice. A potential mechanism for this effect by ginseng is inhibition of DMBA-bioactivating cytochrome P450 (P450) enzymes. In the present in vitro study, we examined the effect of a standardized Panax ginseng (or Asian ginseng) extract (G115), a standardized Panax quinquefolius (or North American ginseng) extract (NAGE), and individual ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) on CYP1 catalytic activities, as assessed by 7-ethoxyresorufin O-dealkylation. G115 and NAGE decreased human recombinant CYP1A1, CYP1A2, and CYP1B1 activities in a concentration-dependent manner. Except for the competitive inhibition of CYP1A1 by G115, the mode of inhibition was the mixed-type in the other cases. A striking finding was that NAGE was 45-fold more potent than G115 in inhibiting CYP1A2. Compared with G115, NAGE also preferentially inhibited 7-ethoxyresorufin O-dealkylation activity in human liver microsomes. Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1, either individually or as a mixture and at the levels reflecting those found in an inhibitory concentration (100 microg/ml) of NAGE or G115, did not influence CYP1 activities. However, at a higher ginsenoside concentration (50 microg/ml), Rb1, Rb2, Rc, Rd, and Rf inhibited these activities. Overall, our in vitro findings indicate that standardized NAGE and G115 extracts, which were not treated with calf serum or subjected to acid hydrolysis, inhibited CYP1 catalytic activity in an enzyme-selective and extract-specific manner, but the effects were not due to Rb1, Rb2, Rc, Rd, Re, Rf, or Rg1.

  Phytosterol content in American ginseng seed oil.:J Agric Food Chem. 2002 Feb 13;50(4):744-50.Beveridge TH, Li TS, Drover JC.Pacific Agri-Food Research Centre, Agriculture and Agri-Food Canada, Summerland, British Columbia, Canada. beveridget@em.agr.ca

 North American ginseng (Panax quinquefolium L.) oil was saponifed and the unsaponifiable matter trimethylsilylated. The phytosterol fraction of hexane-extracted, air-dried seed was quantified and identified by GC and GC-MS. Phytosterol contents (milligrams per 100 g of oil) were as follows: squalene (514-569), oxidosqualene (8.97-48.2), campesterol (9.96-12.4), stigmasterol (93.2-113), clerosterol (1.91-2.14), beta-sitosterol (153-186), beta-amyrin (11.7-19.5), delta(5)-avenasterol (12.4-20.5), delta(5,24(25))-stigmasterol (3.70-.76), lupeol (14.4-15.2), delta(7)-sitosterol (12.5-14.6), delta(7)-avenasterol (4.11-8.09), 24-methylenecycloartanol (1.94-4.76), and citrostadienol (2.50-3.81). Seed stratification lowered the phytosterol levels. Oven-drying gave mixed results, and phytosterols varied slightly between the 1999 and 2000 harvests.


  American ginseng transcriptionally activates p21 mRNA in breast cancer cell lines.:J Korean Med Sci. 2001 Dec;16 Suppl:S54-60.Duda RB, Kang SS, Archer SY, Meng S, Hodin RA.Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. rduda@bidmc.harvard.edu

 American ginseng (AG) has been demonstrated to inhibit breast cancer cell growth in vitro. p21 protein, a universal cell cycle inhibitor, binds cyclin-CDK complexes, an important mechanism in cell cycle regulation. The purpose of this investigation was to determine if AG induces p21 gene expression in hormone sensitive (MCF-7) and insensitive (MDA-MB-231) breast cancer cell lines. Cells grown in steroid stripped medium (SSM) were treated with AG, 17-beta-estradiol (E2), genistein or cycloheximide (CHX). Northern blot analyses were performed using human p21Cip1 and 36B4 cDNA probes. Cell lines were transiently transfected with select mouse p21 CAT reporter constructs, including those lacking a p53 binding site. Cell cycle analyses was performed by FACScan. The results revealed that AG induced p21 mRNA expression in MCF-7 and MDA-MB-231 cells (p=0.0004; p < or =0.0001, respectively). Neither E2 nor genistein alter p21 mRNA expression. CHX, a protein synthesis inhibitor, did not block p21 mRNA expression induced by AG, indicating that p21 is induced as an immediate early gene. AG activated p21 reporter constructs in transfected cells, independent of p53 binding sites. The cell cycle proliferative phase was significantly decreased by AG and increased by E2 (p < or =0.0001). AG may inhibit breast cancer cell growth by transcriptional activation of the p21 gene, independent of p53.

  Immunomodulating activity of CVT-E002, a proprietary extract from North American ginseng (Panax quinquefolium).:J Pharm Pharmacol. 2001 Nov;53(11):1515-23.Wang M, Guilbert LJ, Ling L, Li J, Wu Y, Xu S, Pang P, Shan JJ.CV Technologies Inc, Alberta, Canada.

 The activity of CVT-E002, an aqueous extract containing mainly oligosaccharides and polysaccharides from North American ginseng (Panax quinquefolium), as an immunobooster on murine spleen cells and peritoneal macrophages, was studied in-vitro. CVT-E002 stimulated the proliferation of normal mouse spleen cells, of which the major responding subpopulation was identified as B lymphocytes. CVT-E002 also activated peritoneal exudate macrophages leading to enhanced interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production. In addition, CVT-E002 stimulated in-vivo immunoglobulin G (IgG) production in treated mice. These results identify some of the immunomodulating activities of CVT-E002 and suggest its use clinically for the modulation of immune responses.

  Quantitative determination of ginsenosides by high-performance liquid chromatography-tandem mass spectrometry.:Phytochem Anal. 2001 Sep-Oct;12(5):320-6.Ji QC, Harkey MR, Henderson GL, Gershwin ME, Stern JS, Hackman RM.ThermoQuest Corporation, San Jose, CA 95134, USA.

 An HPLC-MS/MS method was developed for the quantitative determination of ginsenosides, which are the marker compounds for herbal products containing Panax ginseng (Korean or Chinese ginseng) and P. quinquefolius (American ginseng). Samples were extracted with BondElut C18 HF extraction columns and the concentrations of seven major ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) were determined by reversed-phase HPLC-MS/MS employing a quadrupole-ion trap mass spectrometer. Both positive and negative electrospray ionisation techniques were evaluated. Positive ionisation spectra of these compounds gave strong sodium adduct molecular and sodium adduct dimer ions. Negative ionisation yielded the molecular ion primarily and was, therefore, used for analysis: quantitative determination was based on the most abundant product ions for each ginsenoside. The method was used to extract and analyse commercial samples of P. ginseng and P. quinquefolius.

  Konjac-Mannan and American ginsing: emerging alternative therapies for type 2 diabetes mellitus.:J Am Coll Nutr. 2001 Oct;20(5 Suppl):370S-380S; discussion 381S-383S. Review.Vuksan V, Sievenpiper JL, Xu Z, Wong EY, Jenkins AL, Beljan-Zdravkovic U, Leiter LA, Josse RG, Stavro MP.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Ontario, Canada. v.vuksan@utoronto.ca

 Despite significant achievements in treatment modalities and preventive measures, the prevalence of diabetes has risen exponentially in the last decade. Because of these limitations there is a continued need for new and more effective therapies. An increasing number of people are using dietary and herbal supplements, even though there is a general lack of evidence for their safety and efficacy. Consequently, science based medical and government regulators are calling for more randomized clinical studies to provide evidence of efficacy and safety. Our research group has selected two such promising and functionally complementary therapies for further investigation as potentially emerging alternative therapies for type 2 diabetes: Konjac-mannan (KJM) and American ginseng (AG). We have generated a mounting body of evidence to support the claim that rheologically-selected, highly-viscous KJM, and AG with a specific composition may be useful in improving diabetes control, reducing associated risk factors such as hyperlipidemia and hypertension, and ameliorating insulin resistance. KJM has a demonstrated ability to modulate the rate of absorption of nutrients from the small bowel, whereas AG has post-absorptive effects. Consequently, it appears that KJM and AG are acting through different, yet complementary, mechanisms: KJM by increasing insulin sensitivity and AG likely by enhancing insulin secretion. Before the therapeutic potential of KJM and AG as novel prandial agents for treatment of diabetes can be fully realized, further controlled trials with larger sample sizes and of longer duration are required. A determination of the active ingredients in AG, and the rheology-biology relationship of KJM are also warranted.

  Water-soluble ginsenosides in American ginseng.:Zhongguo Zhong Yao Za Zhi. 1998 Sep;23(9):551-2, inside back cover. Chinese.Zhou Y, Song F, Liu S, Li X.Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022.

 OBJECTIVE: To have further comprehension of American Ginseng on the basis of its water-soluble components. METHOD: The water suspension of 80% methanol extract of American Ginseng was sequentially extracted with ethyl ether and n-butyl alcohol. The saccharides in the water-soluble portion were removed by macro-reticular resin column, and three compounds were obtained by silica-gel column chromatography. Their structures were confirmed on the basis of spectral analysis(IR, NMR, MALDI-MS) melting points and optical degrees. RESULT: Three compounds were identified as malonyl ginsenosides Rb1, ginsenoside Rb1 and Re respectively. Among them Rb1 and Re are known, while malonyl ginsenoside Rb1 was isolated from American Ginseng for the first time. Its structure was elucidated as (3 beta, 12 beta)-20-[(-6-O-beta-D- glucopyranosyl-beta-D-glucopyranosyl)oxy]-12-hydroxylammar-24-en-3-yl-O- [6-O-(carboxyacetyl)-beta-D-glucopyranosyl)]-beta-D-glucopyranoside. CONCLUSION: Water-soluble ginsenosides were isolated from the water-soluble extract of American Ginseng suggesting that malonyl ginsenosides exist both in American Ginseng and Ginseng.


  Effects of Panax quinquefolius L. on brainstem neuronal activities: comparison between Wisconsin-cultivated and Illinois-cultivated roots.:Phytomedicine. 2001 May;8(3):178-83.Yuan CS, Wang X, Wu JA, Attele AS, Xie JT, Gu M.Tang Center for Herbal Medicine Research, Pritzker School of Medicine, The University of Chicago, Illinois, USA. cyuan@midway.uchicago.edu

 Brainstem neurons receiving subdiaphragmatic vagal inputs were recorded in an in vitro neonatal rat brainstem-gastric preparation. Aqueous extracts of American ginseng root (Panax quinquefolius L.) from Wisconsin and Illinois were applied to the gastric compartment or the brainstem compartment of the bath chamber to evaluate the peripheral gut or central brain effects of the extracts on brainstem unitary activity. After P. quinquefolius extract application to the gastric or brainstem compartment, a concentration-related inhibition in neuronal discharge frequency in brainstem unitary activity was observed, suggesting that P. quinquefolius plays an important role in regulating the digestive process and modulating the brain function in the rat. In this study, pharmacological effects of Wisconsin-cultivated P. quinquefolius and Illinois-cultivated P. quinquefolius were compared. Our results showed that Illinois-cultivated P. quinquefolius possesses a significantly stronger peripheral gastric as well as central brain modulating effect on brainstem neuronal activity. Data from our high performance liquid chromatography ginsenoside analysis suggest that this increase in inhibitory effects by Illinois-cultivated P. quinquefolius may be due to its different ginsenoside profile.

  Effect of the herbal extract combination Panax quinquefolium and Ginkgo biloba on attention-deficit hyperactivity disorder: a pilot study.:J Psychiatry Neurosci. 2001 May;26(3):221-8.Lyon MR, Cline JC, Totosy de Zepetnek J, Shan JJ, Pang P, Benishin C.Oceanside Functional Medicine Research Institute, Nanaimo, BC.

 OBJECTIVE: A combination herbal product containing American ginseng extract, Panax quinquefolium, (200 mg) and Ginkgo biloba extract (50 mg) (AD-FX; CV Technologies, Edmonton, Alta.) was tested for its ability to improve the symptoms of attention-deficit hyperactivity disorder (ADHD). DESIGN: Open study. PATIENTS: 36 children ranging in age from 3 to 17 years who fit the diagnostic criteria for ADHD. INTERVENTIONS: AD-FX capsules were taken twice a day on an empty stomach for 4 weeks. Patients were instructed not to change any other medications during the study. OUTCOME MEASURES: At the beginning of the study, after 2 weeks, and then at the end of the 4-week trial, parents completed the Conners' Parent Rating Scale--revised, long version, a questionnaire that assesses a broad range of problem behaviours (and was used as an indication of ADHD symptom severity). RESULTS: After 2 weeks of treatment, the proportion of the subjects exhibiting improvement (i.e., decrease in T-score of at least 5 points) ranged from 31% for the anxious-shy attribute to 67% for the psychosomatic attribute. After 4 weeks of treatment, the proportion of subjects exhibiting improvement ranged from 44% for the social problems attribute to 74% for the Conners' ADHD index and the DSM-IV hyperactive-impulsive attribute. Five (14%) of 36 subjects reported adverse events, only 2 of which were considered related to the study medication. CONCLUSIONS: These preliminary results suggest AD-FX treatment may improve symptoms of ADHD and should encourage further research on the use of ginseng and Ginkgo biloba extracts to treat ADHD symptoms.

  Variability in commercial ginseng products: an analysis of 25 preparations.:Am J Clin Nutr. 2001 Jun;73(6):1101-6.Harkey MR, Henderson GL, Gershwin ME, Stern JS, Hackman RM.Department of Medical Pharmacology and Toxicology, the Division of Clinical Immunology, School of Medicine, University of California at Davis, 95616, USA. martha@mother.com

 BACKGROUND: Because dietary supplements are not subject to the same regulations that pharmaceuticals are, there is concern among medical professionals that these products may lack purity or potency. OBJECTIVE: To determine the variability in a range of ginseng herbal products available in the United States, we identified and measured the concentration of marker compounds by using HPLC and liquid chromatography-tandem mass spectrometry. DESIGN: Twenty-five commercial ginseng preparations from the genera Panax or Eleutherococcus were obtained from a local health food store and analyzed for 7 ginsenosides (marker compounds for Panax species, which include Asian and American ginseng) and 2 eleutherosides (marker compounds for Eleutherococcus senticosus, also known as Siberian ginseng). RESULTS: All plant products were correctly identified by botanical plant species (ie, Panax species or E. senticosus); however, concentrations of marker compounds differed significantly from labeled amounts. There was also significant product-to-product variability: concentrations of ginsenosides varied by 15- and 36-fold in capsules and liquids, respectively, and concentrations of eleutherosides varied by 43- and 200-fold in capsules and liquids, respectively. Although a systematic search for adulterants was not conducted, review of the HPLC and liquid chromatography-tandem mass spectrometry data suggest that no substances other than ginsenosides or eleutherosides were extracted from the plant material. CONCLUSION: Our data suggest that US ginseng products are correctly labeled as to plant genus; however, variability in concentrations of marker compounds suggests that standardization may be necessary for quality assurance and that characterization of herbal products should be considered in the design and evaluation of studies on herbal products.

  Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms.:J Agric Food Chem. 2001 May;49(5):2472-9. Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL.Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research, College of Pharmacy, M/C 781, University of Illinois at Chicago, 833 South Wood Street, Chicago, Illinois 60612, USA.

 Eight botanical preparations that are commonly used for the treatment of menopausal symptoms were tested for estrogenic activity. Methanol extracts of red clover (Trifolium pratense L.), chasteberry (Vitex agnus-castus L.), and hops (Humulus lupulus L.) showed significant competitive binding to estrogen receptors alpha (ER alpha) and beta (ER beta). With cultured Ishikawa (endometrial) cells, red clover and hops exhibited estrogenic activity as indicated by induction of alkaline phosphatase (AP) activity and up-regulation of progesterone receptor (PR) mRNA. Chasteberry also stimulated PR expression, but no induction of AP activity was observed. In S30 breast cancer cells, pS2 (presenelin-2), another estrogen-inducible gene, was up-regulated in the presence of red clover, hops, and chasteberry. Interestingly, extracts of Asian ginseng (Panax ginseng C.A. Meyer) and North American ginseng (Panax quinquefolius L.) induced pS2 mRNA expression in S30 cells, but no significant ER binding affinity, AP induction, or PR expression was noted in Ishikawa cells. Dong quai [Angelica sinensis (Oliv.) Diels] and licorice (Glycyrrhiza glabra L.) showed only weak ER binding and PR and pS2 mRNA induction. Black cohosh [Cimicifuga racemosa (L.) Nutt.] showed no activity in any of the above in vitro assays. Bioassay-guided isolation utilizing ER competitive binding as a monitor and screening using ultrafiltration LC-MS revealed that genistein was the most active component of red clover. Consistent with this observation, genistein was found to be the most effective of four red clover isoflavones tested in the above in vitro assays. Therefore, estrogenic components of plant extracts can be identified using assays for estrogenic activity along with screening and identification of the active components using ultrafiltration LC-MS. These data suggest a potential use for some dietary supplements, ingested by human beings, in the treatment of menopausal symptoms.

  Effect of American ginseng extract (Panax quinquefolius) on formalin-induced nociception in mice.:Am J Chin Med. 2001;29(1):149-54.Yang JC, Pang CS, Tsang SF, Ng KF.Department of Anaesthesiology, The University of Hong Kong.

 Twenty-three ICR mice were force fed orally with American ginseng extract, Panax quinquefolius, (Cold FX) for 4 days. Another 20 mice were fed with water as placebo in a similar fashion. Formalin tests which yield typically two phases of pain behavior were done in both groups. Although there was no difference in the first phase between groups, mice treated with Cold FX spent significantly less time in licking and biting of the injured paws in the second phase. The data indicate that American ginseng may have analgesic effect in this chronic pain model.


  Determination of 24(R)-pseudoginsenoside F(11) in North American ginseng using high performance liquid chromatography with evaporative light scattering detection.:J Pharm Biomed Anal. 2001 May;25(2):257-65.Li W, Fitzloff JF.Functional Foods for Health (FFH) Core Analytical Laboratory, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA.

 A gradient liquid chromatographic method with evaporative light scattering detection (ELSD) for the determination of 24(R)-pseudoginsenoside F(11) in North American ginseng is described. Samples are analyzed by means of a reverse-phase column (Waters Spherisorb ODS-2, C(18)) using acetonitrile and water under gradient conditions as the mobile phase over 20 min. The evaporative light scattering detector (ELSD) used, was set at an evaporating temperature of 35 degrees C and nitrogen gas pressure of 3.4 bar. The detection limit (S/N>5) of 24(R)-pseudoginsenoside F(11) is 53 ng on column.

  American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals.:Am J Clin Nutr. 2001 Apr;73(4):753-8.Vuksan V, Sievenpiper JL, Wong J, Xu Z, Beljan-Zdravkovic U, Arnason JT, Assinewe V, Stavro MP, Jenkins AL, Leiter LA, Francis T.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto. v.vuksan@utornto.ca

 BACKGROUND: We previously showed that 3 g American ginseng administered 40 min before an oral glucose challenge significantly reduces postprandial glycemia in subjects without diabetes. Whether this effect can be replicated with doses <3 g and administration times closer to the oral glucose challenge is unclear. OBJECTIVE: Our objective was to study the dosing and timing effects of American ginseng on postprandial glycemia. DESIGN: In a random crossover design, 12 healthy individuals [X +/- SEM age: 42 +/- 7 y; body mass index (BMI; in kg/m2): 24.1 +/- 1.1] received 16 treatments: 0 (placebo), 1, 2, or 3 g American ginseng at 40, 20, 10, or 0 min before a 25-g oral glucose challenge. Capillary blood was collected before administration and at 0, 15, 30, 45, 60, and 90 min after the start of the glucose challenge. RESULTS: Two-way analysis of variance showed that the main effects of treatment and administration time were significant (P < 0.05). Glycemia was lower over the last 45 min of the test after doses of 1, 2, or 3 g ginseng than after placebo (P < 0.05); there were no significant differences between doses. The reductions in the areas under the curve for these 3 doses were 14.4 +/- 6.5%, 10.6 +/- 4.0%, and 9.1 +/- 6%, respectively. Glycemia in the last hour of the test and area under the curve were significantly lower when ginseng was administered 40 min before the challenge than when it was administered 20, 10, or 0 min before the challenge (P < 0.05). CONCLUSIONS: American ginseng reduced postprandial glycemia in subjects without diabetes. These reductions were time dependent but not dose dependent: an effect was seen only when the ginseng was administered 40 min before the challenge. Doses within the range of 1-3 g were equally effective.

  The inhibitory effects of ginsenosides on protein tyrosine kinase activated by hypoxia/reoxygenation in cultured human umbilical vein endothelial cells.:Planta Med. 2001 Feb;67(1):19-23.Dou DQ, Zhang YW, Zhang L, Chen YJ, Yao XS.Department of Natural Products Chemistry, Shenyang Pharmaceutical University, China. doudeqiang@yahoo.com

 27 individual ginsenosides and aglycones, together with five extracts from ginseng roots, ginseng leaves, American ginseng roots, American ginseng leaves and non-saponin fraction from roots of Panax ginseng, were tested for their effects on protein tyrosine kinase (PTK) activation induced by an in vitro hypoxia/reoxygenation (H/R) model in cultured human umbilical vein endothelial cells (HUVEC). The results indicated that ginsenoside-Rb1 (3), -Rd (7), -Ra1 (1) and -Ro (27) showed significant inhibitory effects on PTK activation induced by H/R. Dose-response experiments revealed that ginsenoside-Rb1 was the most active compound and it completely blocked PTK activation at a wide range of concentrations. Most protopanaxadiol-type ginsenosides and some protopanaxatriol-type saponins also showed significant effects on PTK activation. However, the crude extracts did not protect against H/R-induced PTK activation.

  Effects of nitrogen form on American ginseng leaf blight.:Zhongguo Zhong Yao Za Zhi. 1998 Jan;23(1):17-8, 61-2. Chinese.Zhang G, Cheng H, Ding W. Institute of Medicinal Plant, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100094.

 The effects of two nitrogen forms(NO3-N and NH4-N) on American ginseng leaf blight were studied using sand culture method. The results indicated that American ginseng leaf blight caused by Alternaria panax was reduced with NO3-N, while increased with NH4-N.

  Micelle-mediated extraction and preconcentration of ginsenosides from Chinese herbal medicine.:J Chromatogr A. 2000 Dec 22;904(1):47-55.Fang Q, Yeung HW, Leung HW, Huie CW.Department of Chemistry, Hong Kong Baptist University, Kowloon Tong.

 The feasibility of employing micelle-mediated extraction as an alternative and effective method for the solubilization, purification and/or preconcentration of active ingredients from herbal products is demonstrated for the first time using the root of American ginseng as a model. When compared to methanol and water, an aqueous surfactant solution containing 10% Triton X-100 yielded faster kinetics and higher recovery for the extraction of various ginsenosides. An experimental design approach (uniform design) was demonstrated as a novel and useful method for the optimization of experimental factors involved in the micelle-mediated extraction process. For the preconcentration of ginsenosides prior to chromatographic determination, a salting-out agent (sodium sulfate) was employed to make the efficient cloud point extraction of both hydrophobic and hydrophilic ginsenosides into the surfactant-rich phase possible, as well as to increase the preconcentration factor by reducing the volume of the surfactant-rich phase.


  American ginseng improves glycemia in individuals with normal glucose tolerance: effect of dose and time escalation.:J Am Coll Nutr. 2000 Nov-Dec;19(6):738-44.Vuksan V, Stavro MP, Sievenpiper JL, Koo VY, Wong E, Beljan-Zdravkovic U, Francis T, Jenkins AL, Leiter LA, Josse RG, Xu Z.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto and Clinical Nutrition and Risk Factor Modification Centre, St. Michael's Hospital, Ontario, Canada. v.vuksan@utoronto.ca

 OBJECTIVE: We studied the effect of escalating the dose and administration time of American ginseng (AG, Panax quinquefolius L.) in nondiabetic individuals to achieve further improvements in glucose tolerance seen previously when 3 g of AG was taken 40 minutes before a 25 g glucose challenge. METHODS: Ten nondiabetic individuals (6M:4F; mean +/- STD: age = 41 +/- 13 years, BMI = 24.8 +/- 3.5 kg/m2, FBG = 4.5 +/- 0.1 mmol L(-1)) on 12 separate occasions, randomly received 0 (placebo), 3, 6 or 9 g of ground AG root at 40, 80, or 120 minutes before a 25 g oral glucose challenge. Capillary blood glucose was measured prior to ingestion of AG or placebo capsules and at 0, 15, 30, 45, 60 and 90 minutes from start of challenge. RESULTS: Compared with the placebo, 3, 6 and 9 g of AG reduced (p<0.05) postprandial incremental glucose at 30, 45 and 60 minutes; also, 3 and 9 g of AG did so at 90 minutes. At 60 minutes, 9 g of AG reduced incremental postprandial glucose relative to 3 g of AG (p<0.05). All AG doses reduced (p<0.05) area under the incremental glucose curve (3 g, 26.6%; 6 g, 29.3%; 9 g, 38.5%). AG taken at different times did not have an additional influence on postprandial glycemia. CONCLUSIONS: In nondiabetic individuals, 3, 6 or 9 g of AG taken 40, 80 or 120 minutes before a glucose challenge similarly improved glucose tolerance.

  Voltage-dependent inhibition of brain Na(+) channels by American ginseng.:Eur J Pharmacol. 2001 Feb 9;413(1):47-54.Liu D, Li B, Liu Y, Attele AS, Kyle JW, Yuan CS.Department of Neurobiology, Pharmacology and Physiology, The Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.

 American ginseng (Panax quinquefolius) is a major species of ginseng that has many pharmacological effects. Studies have demonstrated that constituents of ginseng have neuroprotective effects during ischemia. Neuronal damage during ischemic episodes has been associated with abnormal Na(+) fluxes. Drugs that block voltage-dependent Na(+) channels provide cytoprotection during cerebral ischemia. We thus hypothesized that American ginseng may block Na(+) channels. In this study, effects of an American ginseng aqueous extract was evaluated in tsA201 cells transfected with cDNA expressing alpha subunits of the Brain(2a) Na(+) channel using the whole-cell patch clamp technique. We found that American ginseng extract tonically and reversibly blocked the channel in a concentration- and voltage-dependent manner. It shifted the voltage-dependence of inactivation by 14 mV (3 mg/ml) in the hyperpolarizing direction and delayed recovery from inactivation, whereas activation of the channel was unaffected. Ginsenoside Rb(1), a major constituent of the American ginseng extract, produced similar effects. The data were compared with the actions of lidocaine, a Na(+) channel blocker. Our results suggest that Na(+) channel block by American ginseng extract and Rb(1) was primarily due to interaction with the inactive state of the channel. Inhibition of the Na(+) channel activity by American ginseng extract may contribute to its neuroprotective effect during ischemia.

  Use of high-performance liquid chromatography-tandem mass spectrometry to distinguish Panax ginseng C. A. Meyer (Asian ginseng) and Panax quinquefolius L. (North American ginseng).:Anal Chem. 2000 Nov 1;72(21):5417-22.Li W, Gu C, Zhang H, Awang DV, Fitzloff JF, Fong HH, van Breemen RB.Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago 60612, USA.

 A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed to distinguish Asian ginseng (Panax ginseng C. A. Meyer) and North American ginseng (Panax quinquefolius L.). The method is based on the baseline chromatographic separation of ginsenoside Rf and 24(R)-pseudoginsenoside F11, two potential chemical markers present in ginseng root methanolic extracts, and their unambiguous on-line identification using tandem mass spectrometry. Consistent with the literature, 24(R)-pseudoginsenoside F11 was detected in abundance in North American ginseng roots in excess of 0.1% (w/w) of the dried root. In contrast to some reports, 24(R)-pseudoginsenoside F11 was also identified in Asian ginseng roots at trace levels using LC-MS-MS but at less than 0.0001% (w/w). Besides showing identical tandem mass spectra to authentic 24(R)-pseudoginsenoside F11, the corresponding compound in Asian ginseng root coeluted with standard under different HPLC conditions, thus confirming this compound as 24(R)-pseudoginsenoside F11. Another ginsenoside often used to distinguish Asian and North American ginseng, ginsenoside Rf, was found in abundance in Asian ginseng roots at more than 0.021% (w/w). In Asian ginseng roots, the ratio of ginsenoside Rf to 24(R)-pseudoginsenoside F11 exceeded 700:1. The limit of detection of ginsenoside Rf or 24(R)-pseudoginsenoside F11 was 120 pg injected on-column, and the limit of quantification was 240 pg on-column. In summary, LC-MS-MS analysis of ginseng products for the presence and ratio of ginsenoside Rf and 24(R)-pseudoginsenoside F11 may be used for the unambiguous identification of Asian and North American ginsengs.

  Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes.:Diabetes Care. 2000 Sep;23(9):1221-6.Vuksan V, Stavro MP, Sievenpiper JL, Beljan-Zdravkovic U, Leiter LA, Josse RG, Xu Z.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada. v.vuksan@utoronto.ca

 OBJECTIVE: We previously demonstrated that 3 g American ginseng (AG) reduced postprandial glycemia (PPG) in type 2 diabetic individuals. We investigated whether further reductions can be achieved with escalation of dose and time of AG administration. RESEARCH DESIGN AND METHODS: Ten type 2 diabetic patients (6 men, 4 women; age 63+/-2 years; BMI 27.7+/-1.5 kg/m2; HbA1c 7.3+/-0.3%) were randomly administered 0 g (placebo) or 3, 6, or 9 g ground AG root in capsules at 120, 80, 40, or 0 min before a 25-g oral glucose challenge. Capillary blood glucose was measured before ingestion of AG or placebo and at 0, 15, 30, 45, 60, 90, and 120 min from the start of the glucose challenge. RESULTS: Two-way analysis of variance (ANOVA) demonstrated that treatment (0, 3, 6, and 9 g AG) but not time of administration (120, 80, 40, or 0 min before the challenge) significantly affected PPG (P<0.05), with significant (P = 0.037) interaction for area under the curve (AUC). Pairwise comparisons showed that compared with 0 g (placebo), 3, 6, or 9 g significantly (P<0.05) reduced AUC (19.7, 15.3, and 15.9%, respectively) and incremental glycemia at 30 min (16.3, 18.4, and 18.4%, respectively), 45 min (12.5, 14.3, and 14.3%, respectively), and 120 min (59.1, 40.9, and 45.5%, respectively). However, pairwise comparisons showed no differences between the 3-, 6-, or 9-g doses and any of the times of administration. CONCLUSIONS: AG reduced PPG irrespective of dose and time of administration. No more than 3 g AG was required at any time in relation to the challenge to achieve reductions. Because these reductions included glycemia at the 2-h diagnostic end point, there may be implications for diabetes diagnosis and treatment.

  Selected herbals and human exercise performance.:Am J Clin Nutr. 2000 Aug;72(2 Suppl):624S-36S. Review.Bucci LR.Weider Nutrition International, Salt Lake City, UT 84104-4726, USA. lukeb@weider.com

 Herbs have been used throughout history to enhance physical performance, but scientific scrutiny with controlled clinical trials has only recently been used to study such effects. The following herbs are currently used to enhance physical performance regardless of scientific evidence of effect: Chinese, Korean, and American ginsengs; Siberian ginseng, mahuang or Chinese ephedra; ashwagandha; rhodiola; yohimbe; CORDYCEPS: fungus, shilajit or mummio; smilax; wild oats; Muira puama; suma (ecdysterone); Tribulus terrestris; saw palmetto berries; beta-sitosterol and other related sterols; and wild yams (diosgenin). Controlled studies of Asian ginsengs found improvements in exercise performance when most of the following conditions were true: use of standardized root extracts, study duration (>8 wk, daily dose >1 g dried root or equivalent, large number of subjects, and older subjects. Improvements in muscular strength, maximal oxygen uptake, work capacity, fuel homeostasis, serum lactate, heart rate, visual and auditory reaction times, alertness, and psychomotor skills have also been repeatedly documented. Siberian ginseng has shown mixed results. Mahuang, ephedrine, and related alkaloids have not benefited physical performance except when combined with caffeine. Other herbs remain virtually untested. Future research on ergogenic effects of herbs should consider identity and amount of substance or presumed active ingredients administered, dose response, duration of test period, proper experimental controls, measurement of psychological and physiologic parameters (including antioxidant actions), and measurements of performance pertinent to intended uses.


  American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus.:Arch Intern Med. 2000 Apr 10;160(7):1009-13.Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan-Zdravkovic U, Xu Z, Vidgen E.Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, St. Michael's Hospital, Ontario, Canada. v.vuksan@utoronto.ca

 BACKGROUND: Despite a lack of medical evidence to support its therapeutic efficacy, the use of herbal medicine has increased considerably. Ginseng, one of the most widely used herbs, is hypothesized to play a role in carbohydrate metabolism and diabetes mellitus. We therefore undertook a preliminary short-term clinical study to assess whether American ginseng (Panax quinquefolius L) affects postprandial glycemia in humans. DESIGN: On 4 separate occasions, 10 nondiabetic subjects (mean [+/-SD] age, 34+/-7 years; mean [+/-SD] body mass index [BMI], 25.6 +/- 3 kg/m2) and 9 subjects with type 2 diabetes mellitus (mean [+/-SD] age, 62 +/- 7 years; mean [+/-SD] BMI, 29 +/- 5 kg/m2; mean [+/-SD] glycosylated hemoglobin A1c, 0.08+/-0.005) were randomized to receive 3-g ginseng or placebo capsules, either 40 minutes before or together with a 25-g oral glucose challenge. The placebo capsules contained com flour, in which the quantity of carbohydrate and appearance matched the ginseng capsules. A capillary blood sample was taken fasting and then at 15, 30, 45, 60, 90, and 120 (only for subjects with type 2 diabetes mellitus ) minutes after the glucose challenge. RESULTS: In nondiabetic subjects, no differences were found in postprandial glycemia between placebo and ginseng when administered together with the glucose challenge. When ginseng was taken 40 minutes before the glucose challenge, significant reductions were observed (P<.05). In subjects with type 2 diabetes mellitus, the same was true whether capsules were taken before or together with the glucose challenge (P<.05). Reductions in area under the glycemic curve were 18%+/-31% for nondiabetic subjects and 19+/-22% and 22+/-17% for subjects with type 2 diabetes mellitus administered before or together with the glucose challenge, respectively. CONCLUSIONS: American ginseng attenuated postprandial glycemia in both study groups. For nondiabetic subjects, to prevent unintended hypoglycemia it may be important that the American ginseng be taken with the meal.

  Differentiation and authentication of Panax ginseng, Panax quinquefolius, and ginseng products by using HPLC/MS.:Anal Chem. 2000 Mar 15;72(6):1281-7. Erratum in: Anal Chem 2000 May 15;72(10):2329.Chan TW, But PP, Cheng SW, Kwok IM, Lau FW, Xu HX.Chinese Medicinal Material Research Centre, Department of Chemistry, Chinese University of Hong Kong, Shatin, NT, Hong Kong.

 An LC/MS-based method is established for the differentiation and authentication of specimens and commercial samples of Panax ginseng (Oriental ginseng) and Panax quinquefolius (American ginseng). This method is based on the separation of ginsenosides present in the ginseng methanolic extracts using high-performance liquid chromatography (HPLC), followed by detection with electrospray mass spectrometry. Differentiation of ginsenosides is achieved through simultaneous detection of intact ginsenoside molecular ions and the ions of their characteristic thermal degradation products. An important parameter used for differentiating P. ginseng and P. quinquefolius is the presence of ginsenoside Rf and 24-(R)-pseudoginsenoside F11 in the RICs of Oriental and American ginsengs, respectively. It is important to stress that ginsenoside Rf and 24(R)-pseudoginsenoside F11, which possess the same molecular weight and were found to have similar retention times under most LC conditions, can be unambiguously distinguished in the present HPLC/MS method. The method developed is robust, reliable, reproducible, and highly sensitive down to the nanogram level.

  Antioxidant properties of a North American ginseng extract.:Mol Cell Biochem. 2000 Jan;203(1-2):1-10.Kitts DD, Wijewickreme AN, Hu C.Food, Nutrition and Health, Faculty of Agricultural Sciences, University of British Columbia, Vancouver, Canada.

 A North American ginseng extract (NAGE) containing known principle ginsenosides for Panax quinquefolius was assayed for metal chelation, affinity to scavenge DPPH-stable free radical, and peroxyl (LOO*) and hydroxyl (*OH) free radicals for the purpose of characterizing mechanisms of antioxidant activity. Dissociation constants (Kd) for NAGE to bind transition metals were in the order of Fe2+ > Cu2+ > Fe3+ and corresponded to the affinity to inhibit metal induced lipid peroxidation. In a metal-free linoleic acid emulsion, NAGE exhibited a significant (p < or = 0.05) concentration (0.01-10 mg/mL) dependent mitigation of lipid oxidation as assessed by the ammonium thiocyanate method. Similar results were obtained when NAGE was incubated in a methyl linoleate emulsion containing haemoglobin catalyst and assessed by an oxygen electrode. NAGE also showed strong DPPH radical scavenging activity up to a concentration of 1.6 mg/mL (r2 = 0.996). Similar results were obtained for scavenging of both site-specific and non site-specific *OH, using the deoxyribose assay method. Moreover, NAGE effectively inhibited the non site-specific DNA strand breakage caused by Fenton agents, and suppressed the Fenton induced oxidation of a 66 Kd soluble protein obtained from mouse brain over a concentration range of 2-40 mg/mL. These results indicate that NAGE exhibits effective antioxidant activity in both lipid and aqueous mediums by both chelation of metal ions and scavenging of free radicals.

  Interactions between Panax quinquefolium saponins and vitamin C are observed in vitro.:Mol Cell Biochem. 2000 Jan;204(1-2):77-82.Li JP, Huang M, Teoh H, Man RY.Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, SAR, China.

 Inasmuch as the oxidation of low-density lipoprotein (Ox-LDL) may play a key role in the initiation and progression of atherosclerosis, it has become increasingly important to identify potential antioxidants. Panax quinquefolium saponins (PQS) are extracted from the stems and leaves of the North American form of ginseng, Panax quinquefolium. Our previous studies have indicated that PQS (0.25-1 mg/ml) can protect against oxidation of LDL in vitro. The purpose of the current work was to investigate the potential interaction of lower concentrations of PQS (1-100 microg/ml) with vitamin C on the reduction of LDL oxidation. LDL was isolated from the plasma of healthy human donors by sequential ultracentrifugation. Native LDL (0.05 or 0.2 mg/ml) was incubated with PQS and/or vitamin C for 30 min at 20 degrees C. Oxidative modification was initiated with 2 microM or 5 microM CuSO4 at 37 degrees C for (0-24 h. Pretreatment with PQS (100 microg/ml) reduced alterations in phospholipids, lipid peroxide levels and relative electrophoretic mobility of Ox-LDL. The presence of vitamin C (1-10 microM) significantly enhanced the protective effects of PQS. Pretreatment with PQS (1-100 microg/ml) resulted in concentration-dependent inhibition of LDL oxidation and prolongation of lag time as determined from measurements of conjugated lipid hydroperoxide content in Ox-LDL samples. Interestingly, the inhibitory actions of lower amounts of PQS (1 and 10 microg/ml) on the formation of conjugated dienes were significantly increased when vitamin C (0.1 or 1 microM) was present. In conclusion, our results suggest that PQS not only have direct antioxidant property but at low concentrations, their actions can be enhanced by vitamin C.

  Quinqueginsin, a novel protein with anti-human immunodeficiency virus, antifungal, ribonuclease and cell-free translation-inhibitory activities from American ginseng roots.:Biochem Biophys Res Commun. 2000 Mar 5;269(1):203-8.Wang HX, Ng TB.Department of Microbiology, China Agricultural University, Beijing, China.

 A homodimeric protein designated quinqueginsin, with a molecular weight of 53 kDa, has been isolated from the roots of American ginseng Panax quinquefolium. It was unadsorbed on DEAE cellulose in low ionic strength and neutral pH, and adsorbed on Affigel blue gel and SP-Sepharose under similar conditions. Its N-terminal sequence bore similarity to those of plant ribosome inactivating proteins and fungal ribonucleases. The protein displayed a variety of biological activities. It possessed ribonucleolytic activity toward yeast tRNA and specific activity toward poly C. It inhibited cell-free translation in a rabbit reticulocyte lysate system with an IC(50) of 0.26 nM, and exerted antifungal action against Fusarium oxysporum, Rhizoctonia solani, and Coprinus comatus. An inhibitory action was expressed toward human immunodeficiency virus-1 reverse transcriptase. This action was potentiated after chemical modification with succinic anhydride.


  Simultaneous quantification of ginsenosides in American ginseng (Panax quinquefolium) root powder by visible/near-infrared reflectance spectroscopy.:J Agric Food Chem. 1999 Jul;47(7):2771-5.Ren G, Chen F.Department of Botany, The University of Hong Kong, Pokfulam Road, Hong Kong.

 Near-infrared reflectance spectroscopy (NIRS) was examined as a possible alternative to high-performance liquid chromatography (HPLC) for the analysis of ginsenosides from American ginseng (Panax quinquefolium) root powder (n = 26). NIR spectra were collected over 400-2500 nm. For each sample and individual ginsenoside quantified by HPLC, spectral data were regressed against the chemical data to develop prediction equations. The spectral prediction equations produced high correlation coefficient (1-VR) values and low standard errors of cross validation (SECV) values for the determination of individual and total ginsenosides. The contents of individual ginsenosides, Rb(1), Rb(2), Rc, Rd, Re, Rg(1), Ro, m-Rb(1), m-Rb(2), m-Rc, m-Rd, and total ginsenosides (X +/- SECV) were (1.29+/-0.18)%, (0.273+/-0.096)%, (0.298+/-0.052)%, (0.091+/-0.027)%, (1. 015+/-0.114)%, (0.116+/-0.018)%, (0.25+/-0.040)%, (0.776+/-0.116)%, (0.197+/-0.074)%, (0.239+/-0.083)%, (0.143+/-0.042)%, and (4.393+/-0.283)%, respectively. The (1-VR) values of cross validation were 0.877, 0.872, 0.955, 0.834, 0.899, 0.919, 0.325, 0.849, 0.902, 0.877, 0.871, and 0.963, respectively. Results indicated that the NIRS method could be used for the analysis of the major ginsenosides, Rb(1), Re, and m-Rb(1), as well as the total ginsenosides in American ginseng.

  Panax quinquefolium L. inhibits thrombin-induced endothelin release in vitro.:Am J Chin Med. 1999;27(3-4):331-8.Yuan CS, Attele AS, Wu JA, Lowell TK, Gu Z, Lin Y.Committee on Clinical Pharmacology, Pritzker School of Medicine, University of Chicago, IL 60637, USA.

 Endothelial cell damage is considered to be the initial step in the genesis of thrombosis and arteriosclerosis, the common precursors of cardiovascular disorders. In this study, we evaluated the protective effects of American ginseng or Panax quinquefolium L. extracts on endothelial cell injury, and investigated effects of ginseng extracts on thrombin-induced endothelin release using cultured human umbilical vein endothelial cells. We observed that when endothelial cells pretreated with 1, 10, and 100 micrograms/ml of Panax quinquefolium L. extracts were incubated for 4 and 24 hr with thrombin, the concentration of endothelin was significantly decreased in a concentration dependent, time related manner (at 4 hr, IC50 = 5.1 micrograms/ml; at 24 hr, IC50 = 6.2 micrograms/ml). We further evaluated the effects of NG-nitro-L-arginine (NLA), a nitric oxide (NO) synthetase inhibitor, on the activity of Panax quinquefolium L. extracts. Following pretreatment of cultured endothelial cells with NLA, the inhibition of thrombin-induced endothelin release by Panax quinquefolium L. was significantly reduced (P < 0.05). This result suggests that the pharmacological action of Panax quinquefolium L. is, at least partially, due to NO release. Our data demonstrate that American ginseng may play a therapeutic role in facilitating the hemodynamic balance of vascular endothelial cells.

  American ginseng and breast cancer therapeutic agents synergistically inhibit MCF-7 breast cancer cell growth.:J Surg Oncol. 1999 Dec;72(4):230-9.Duda RB, Zhong Y, Navas V, Li MZ, Toy BR, Alavarez JG.Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. rduda@bidmc.harvard.edu

 BACKGROUND AND OBJECTIVES: American ginseng (Panax quinquefolius L.) purportedly alleviates menopause symptoms because of putative estrogenicity. METHODS: Using a standardized American ginseng (AG) extract in MCF-7 breast cancer cells, the objectives were to evaluate the ability of AG to induce the estrogen- regulated gene pS2 by Northern blot analysis, determine the effect on cell growth using the MTT assay, and evaluate the cell cycle effects by flow cytometry. RESULTS: AG and estradiol equivalently induced RNA expression of pS2. AG, in contrast to estradiol, caused a dose-dependent decrease in cell proliferation (P < 0.005). AG had no adverse effect on the cell cycle while estradiol significantly increased the proliferative phase (percent S-phase) and decreased the resting phase (G(0)-G(1) phase) (P < 0.005). Concurrent use of AG and breast cancer therapeutic agents resulted in a significant (P < 0.005) suppression of cell growth for most drugs evaluated. CONCLUSIONS: In vitro use of AG and breast cancer therapeutics synergistically inhibited cancer cell growth.

  American ginseng extract reduces scopolamine-induced amnesia in a spatial learning task.:J Psychiatry Neurosci. 1999 Nov;24(5):442-52.Sloley BD, Pang PK, Huang BH, Ba F, Li FL, Benishin CG, Greenshaw AJ, Shan JJ.CV Technologies, Edmonton, Alta. Duff@cvtechnologies.com

 OBJECTIVE: To determine if HT-1001, an extract of American ginseng, affects scopolamine-induced memory and performance deficits in a spatial learning task, alters brain concentrations of aminergic neurotransmitters, and alters choline uptake in synaptosome preparations. DESIGN: Animal study. ANIMALS: 48 Sprague Dawley rats. INTERVENTIONS: Long-term oral administration of a test material or control solution. Intraperitoneal administration of scopolamine (2 mg/kg) 30 minutes before testing. OUTCOME MEASURES: Performance on Morris water maze task, choline uptake, aminergic neurotransmitter analysis, in vitro monoamine oxidase analysis (of compounds). RESULTS: HT-1001 protected against scopolamine-induced amnesia and increased choline uptake in synaptosomal preparations. HT-1001 did not alter brain concentrations of norepinephrine, dopamine, 5-HT (serotonin), 3,4-dihydroxyphenylacetic acid or 5-hydroxyindoleactic acid. HT-1001 had a very weak ability to inhibit monoamine oxidase activity in vitro. CONCLUSIONS: HT-1001 demonstrates a capacity to protect against scopolamine-induced memory deficits.

  Medicinal herbs: NTP extracts the facts.:Environ Health Perspect. 1999 Dec;107(12):A604-5.No authors listed

 The National Toxicology Program (NTP) has announced that it will design and initiate studies to identify and characterize possible adverse health effects that may be associated with prolonged use or higher doses of some of the most popular medicinal herbs, including Ginkgo biloba, Echinacea angustifolia, and Panax quinquefolius (American ginseng). The NTP studies a large variety of substances to which the population may be exposed in the environment, occupationally, in the food supply, or elsewhere.


  Degradation of ginsenosides in American ginseng (Panax quinquefolium) extracts during microwave and conventional heating.:J Agric Food Chem. 1999 Apr;47(4):1501-5.Ren G, Chen F.Department of Botany, The University of Hong Kong.

 The degradation of ginsenosides in American ginseng (Panax quinquefolium) extracts during microwave and water (oil) bath heating (conventional heating) was investigated. Both the 50% ethanol-water extracts and the aqueous extracts were boiled in a modified laboratory microwave oven and in a water (or oil) bath, respectively. The neutral ginsenosides (Rb(1), Rc, Rd, and Re) and malonyl ginsenosides (m-Rb(1), m-Rc, and m-Rd) were determined by reverse-phase high-performance liquid chromatography. The results showed that the degradation of ginsenosides in 50% ethanol-water extracts was a first-order reaction. The malonyl ginsenosides were much less stable than the corresponding neutral ginsenosides, with the rate constant value of the malonyl ginsenosides being 3-60 times that of the neutral ginsenosides. At the same temperature, the effect of microwave heating on the degradation of ginsenosides was the same as that of conventional heating.

  Pollen ultrastructure of Panax(the ginseng genus, Araliaceae),an eastern Asian and eastern NorthAmerican disjunct genus.:Am J Bot. 1999 Nov;86(11):1624.Wen J, Nowicke JW.Department of Biology, Colorado State University, Fort Collins, Colorado 80523 Department of Botany, NHB-166, Smithsonian Institution, Washington, D.C. 20560.

 Pollen of ten species of Panax and six species of Aralia was examined in light microscopy and scanning and transmission electron microscopy. Grains of both genera have similar complex apertures, short columellae, and overlapping tectal sculptures, suggesting a close relationship. Most species of Panax have pollen characterized by striato-reticulate tecta, short columellae, thick foot layers, costa ectocolpi, and lalongate endoapertures. The eastern North American P. trifolius, commonly known as the dwarf ginseng, has a distinctive pollen morphology and exine structure, supporting the hypothesis of its phylogenetically isolated position. Pollen of the eastern Asian P. ginseng (ginseng) can be distinguished from the eastern North American P. quinquefolius (American ginseng) by differences in ultrastructure. The monophyly of the three medicinally important species, P. ginseng, P. notoginseng, and P. quinquefolius, suggested by triterpenoid data, is not supported by pollen data. The results of the pollen study are generally congruent with those from the sequences of nuclear ribosomal DNA.

  Determination of ginsenosides in plant extracts from Panax ginseng and Panax quinquefolius L. by LC/MS/MS.:Anal Chem. 1999 Apr 15;71(8):1579-84.Wang X, Sakuma T, Asafu-Adjaye E, Shiu GK.Perkin-Elmer Sciex Instruments, Concord, Ontario, Canada.

 An HPLC/MS/MS method has been developed for the characterization and quantification of ginsenosides contained in extracts of the root of Panax ginseng (Korean ginsengs) and Panax quinquefolius L. (American ginsengs). The [M + H]+ and [M + Na]+ ions were observed for ginsenoside standards (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1) and four different ginseng extracts. The glycosidic linkages, the core, and the attached sugar(s) of the ginsenosides can be determined from the collision-induced dissociation spectra from the protonated molecules. The relative distribution of these ginsenosides in each extract of American or Korean ginseng was established.

  Panax quinquefolium saponins protects low density lipoproteins from oxidation.:Life Sci. 1999;64(1):53-62.Li J, Huang M, Teoh H, Man RY.Department of Pharmacology, The University of Hong Kong, China.

 Oxidized low-density lipoprotein (Ox-LDL) is believed to be involved in the pathogenesis of atherosclerosis. Panax quinquefolium saponins (PQS) are extracted from the stems and leaves of the North American form of ginseng, Panax quinquefolium. Earlier studies have suggested that this extract improves the lipid profile of hyperlipidemic rats and has antioxidant properties in cultured rat cardiac myocytes. The aims of the present study were to investigate the potential of PQS in reducing LDL oxidation as well as limiting the ability of Ox-LDL to impair endothelium-dependent relaxation in rat aortic rings. LDL was isolated from the plasma of healthy human donors by sequential ultracentrifugation. Native LDL (0.2 or 0.3 mg/ml) was incubated with PQS (0.25-1 mg/ml) for 30 min at 20 degrees C. For comparison, vitamin C (50 microM) was added in place of PQS. Oxidative modification was initiated with 5 microM CuSO4 at 37 degrees C for 0-24 h. In our hands, PQS concentration-dependently reduced lipid peroxide levels as measured by the amount of thiobarbituric acid reactive substances formed. This range of PQS also retarded the alterations in relative electrophoretic mobility of Ox-LDL in a similar manner. Furthermore, measurement of phospholipid fractions content indicated that PQS could reduce the conversion of phosphatidylcholine to lysophosphatidylcholine in Ox-LDL. Functional studies demonstrated that PQS-pretreated Ox-LDL was less potent than untreated Ox-LDL at impairing endothelium-dependent relaxation in rat aortic rings. In conclusion, our results suggest that PQS has antioxidant properties and that reduction of LDL oxidation by PQS may provide a protective effect against the detrimental actions of Ox-LDL.

  Modulation of American ginseng on brainstem GABAergic effects in rats.:J Ethnopharmacol. 1998 Oct;62(3):215-22.Yuan CS, Attele AS, Wu JA, Liu D.Department of Anesthesia and Critical Care, The Pritzker School of Medicine, The University of Chicago, IL 60637, USA. cyuan@midway.uchicago.edu

 Single neurons in the region of the medial nucleus tractus solitarius (NTS), responding or not responding to gastric vagal branch stimulation, were recorded in an in vitro neonatal rat brainstem-gastric preparation. The spontaneous activity of the majority of these two types of NTS units was inhibited by GABA(A) receptor agonist, muscimol (30 microM), and this inhibition (approximately 52% compared to 100% of the control level) could be antagonized by selective GABA(A) receptor antagonist, bicuculline (10 microM). Application of Panax quinquefolium L. extracts (3.0 microg/ml) into the brainstem compartment of the preparation also significantly reduced the discharge rate of these NTS neurons (approximately 27% compared to the control level), but this reduction could not be reversed by bicuculline (10 microM). Pretreatment with Panax quinquefolium L. (3.0 microg/ml) significantly decreased the NTS inhibitory effects induced by muscimol (30 microM), approximately from 51 to 33%. Our results demonstrated the interactions of Panax quinquefolium L. with ligand-bindings of GABA(A) receptors, and the modulation of the brainstem GABAergic mechanism by Panax quinquefolium L. Our data suggest that the regulation of GABAergic neurotransmission may be an important action of Panax quinquefolium L.


  Effect of American ginseng (Panax quinquefolium) on male copulatory behavior in the rat.:Physiol Behav. 1998 Jun 15;64(4):445-50.Murphy LL, Cadena RS, Ch¨¢vez D, Ferraro JS.Department of Physiology, Southern Illinois University School of Medicine, Carbondale 62901-6512, USA. lmurphy@som.siu.edu

 The effects of American ginseng (Panax quinquefolium) on male rat copulatory behavior were investigated. Adult Sprague-Dawley rats were administered either 10, 50 or 100 mg/kg of Panax quinquefolium or a sesame oil vehicle per os (p.o.) for 28 days and copulatory behavior parameters were measured. Ginseng-treated male rats demonstrated a significant decrease in mount, intromission and ejaculation latencies compared to vehicle controls. Hormone analyses revealed no difference in plasma luteinizing hormone or testosterone levels between ginseng- and vehicle-treated animals; however, plasma prolactin levels were significantly reduced by all doses of ginseng tested. When male rats were treated with the 100 mg/kg dose of ginseng for 1, 14 or 28 days, mount and intromission latencies were significantly reduced at 14 and 28 days of daily ginseng treatment, whereas ejaculation latency was significantly reduced after 1 day of ginseng treatment when compared to vehicle controls. Plasma prolactin levels were also significantly decreased after 14 and 28 days of daily ginseng administration. There were no differences in body weight or in testes, seminal vesicle, anterior pituitary or spleen weights between ginseng- and vehicle-treated rats. These results demonstrate that P. quinquefolium significantly facilitates male copulatory behavior. The reduction in plasma prolactin levels suggests that ginseng-induced alterations in dopaminergic neurotransmission may play a role in the ability of P. quinquefolium to stimulate copulatory behavior in the male rat.

  Gut and brain effects of American ginseng root on brainstem neuronal activities in rats.:Am J Chin Med. 1998;26(1):47-55.Yuan CS, Wu JA, Lowell T, Gu M. Department of Anesthesia and Critical Care, Pritzker School of Medicine, University of Chicago, IL 60637, USA.

 Brainstem neurons receiving subdiaphragmatic vagal inputs were recorded in an in vitro neonatal rat brainstem-gastric preparation. Aqueous extracts of American ginseng root (Panax quinquefolium L.) were applied to the gastric compartment or the brainstem compartment of the bath chamber to evaluate the peripheral gut and central brain effects of the extracts on brainstem unitary activity. After Panax quinquefolium L. application to the gastric or brainstem compartment, a concentration-related inhibition in neuronal discharge frequency in the brainstem unitary activity was observed, suggesting that Panax quinquefolium L. may play an important role in regulating the digestive process and modulating brain function. In this study, pharmacological effects of American-cultivated Panax quinquefolium L. and Chinese-cultivated Panax quinquefolium L. were also compared. Our results suggest that American-cultivated Panax quinquefolium L. possesses a significantly stronger gastric modulating effect on brain neuronal activity.

  Bioactive saponins and glycosides. XI. Structures of new dammarane-type triterpene oligoglycosides, quinquenosides I, II, III, IV, and V, from American ginseng, the roots of Panax quinquefolium L.:Chem Pharm Bull. 1998 Apr;46(4):647-54.

 The methanolic extract and 1-butanol-soluble fraction of American ginseng, the roots of Panax quinquefolium L., were found to exhibit a protective effect on liver injury induced by D-galactosamine and lipopolysaccharide. Five new dammarane-type triterpene oligoglycosides called quinquenosides I, II, III, IV, and V were isolated together with fourteen known dammarane-type triterpene oligoglycosides such as chikusetsusaponin IVa, pseudo-ginsenoside-RC1, malonyl-ginsenoside-Rb1, and notoginsenosides-A,-C, and -K from the 1-butanol-soluble fraction. From the ethyl acetate-soluble fraction, four known acetylenic compounds and 6'-O-acetyl ginsenoside-Rg1 were isolated. The structures of quinquenosides I, II, III, IV, and V were determined on the basis of chemical and physicochemical evidence as 3-O-[6-O-(E)-2-butenoyl-beta-D-glucopyranosyl(1-->2)-beta-D- glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol (quinquenoside I), 3-O-[6-O-(E)-2-octenoyl-beta-D- glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 20(S)-protopanaxadiol (quinquenoside II), 3-O-[beta-D-glucopyranosyl (1-->2)-6-O-acetyl-beta-D-glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol (quinquenoside III), 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl]-3 beta, 7 beta, 20(S)-trihydroxydammar-5,24-diene (quinquenoside IV), and 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[alpha-D- glucopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ] 20(S)-protopanaxadiol (quinquenoside V).

  Ginsenoside Rb1 regulates ChAT, NGF and trkA mRNA expression in the rat brain.:Brain Res Mol Brain Res. 1997 Jul;47(1-2):177-82.Salim KN, McEwen BS, Chao HM.Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA.

 Ginsenoside Rb1 (Rb1), a saponin of North American ginseng (Panax quinquefolium L.), has been found to exert beneficial effects on memory and learning, putatively through its actions on the cholinergic system. In situ hybridization studies show that Rb1 increases the expression of choline acetyltransferase and trkA mRNAs in the basal forebrain and nerve growth factor mRNA in the hippocampus. Other neurotrophins (brain-derived neurotrophic factor, neurotrophin-3), genes encoding neuropeptides (preproenkephalin, preprotachykinin) and amyloid protein precursor were also studied, but no significant change was observed. These findings support the specificity of the effects of Rb1 on certain aspects of the cholinergic and neurotrophic systems.

  18S ribosomal RNA gene sequences of three Panax species and the corresponding ginseng drugs.:Biol Pharm Bull. 1996 Nov;19(11):1530-2.

 Total DNA was extracted from the fresh underground parts of three Panax separate species. The 18S rRNA regions of extracted DNA were amplified by the polymerase chain reaction (PCR) and their sequences were determined. In each species, the sequences were found to be of 1809 base pairs (bps) but with different gene sequences. Different base substitutions were observed at nucleotide positions 497, 499, 501 and 712. The same procedure was performed on commercial samples of Ginseng Radix, Panacis Japonici Rhizoma and American Ginseng. Each sequence completely corresponded with that of each original plant, namely P. ginseng, P. japonicus and P. quinquefolius, respectively. This is the first time that 18S rRNA gene sequencing on Panax species was carried out. Previously, Ginseng drugs have been identified mainly by their external and internal structure. Thus this method will be useful in identifying Ginseng drugs at the gene level.


  pS2 expression induced by American ginseng in MCF-7 breast cancer cells.:Ann Surg Oncol. 1996 Nov;3(6):515-20.Duda RB, Taback B, Kessel B, Dooley DD, Yang H, Marchiori J, Slomovic BM, Alvarez JG.Division of Surgical Oncology, Beth Israel Hospital, Harvard Medical School, Boston, MA, USA.

 BACKGROUND: Alternative medicines are frequently used by patients with breast cancer for general health benefits. American ginseng, an herbal remedy, purportedly alleviates treatment-induced postmenopausal symptoms. METHODS: Estrogenic potential of American ginseng root extract to induce the expression of pS2, an estrogen-regulated gene, was evaluated in breast cancer cell lines MCF-7, T-47D, and BT-20 by Northern and Western blot analysis. Competitive studies were performed with ginseng in combination with tamoxifen. Cell proliferation assays were performed using the tetrazolium dye procedure and direct cell count. RESULTS: Ginseng and estradiol induce the expression of pS2 RNA and protein in MCF-7 cells, whereas tamoxifen suppresses expression. Neither ginseng nor estradiol induced increased pS2 expression in T-47D or BT-20 cell lines. Although estradiol exhibited a proliferative effect and tamoxifen had an inhibitory effect, ginseng demonstrated no significant effect on cell proliferation. CONCLUSIONS: The results of this study suggest that ginseng may exhibit estrogenlike effects on estrogen receptor-positive breast cancer cells by inducing pS2 expression and that the effect of ginseng may be mediated in part through the estrogen receptor. Because ginseng does not exhibit a proliferative effect, it may play a protective role against breast cancer rather than serve as a mitogen.

  Phylogeny and biogeography of Panax L. (the ginseng genus, araliaceae): inferences from ITS sequences of nuclear ribosomal DNA.:Mol Phylogenet Evol. 1996 Oct;6(2):167-77.Wen J, Zimmer EA.Laboratory of Molecular Systematics, National Museum of Natural History, Smithsonian Institution, Washington, DC 20560, USA.

 Panax, the ginseng genus, is one of the most medicinally important genera in the Orient and demonstrates a classical eastern Asian and eastern North American disjunct distributional pattern. Sequences of the internal transcribed spacers (ITS) and the 5.8S coding region of the nuclear ribosomal DNA repeat were obtained for the 12 species of Panax to reconstruct phylogenetic relationships. Of the 2 eastern North American species, P. quinquefolius and P. trifolius, P. quinquefolius was suggested to be more closely related to the eastern Asian species in the ITS tree, while P. trifolius was phylogenetically isolated. Monophyly of the three medicinally most important species, P. ginseng, P. notoginseng, and P. quinquefolius, suggested by previous workers, was not supported by the ITS data. A close phylogenetic relationship between Panax and Aralia was supported. Several biogeographical implications were inferred: (1) two divergence events have produced the eastern Asian and eastern North American disjunct distribution in Panax, (2) no intercontinental species pairs are found in Panax; (3) a discrepancy between the sequence divergence pattern and the phylogenetic pattern was observed in Panax, suggesting the need for caution in using sequence divergence data alone in inferring biogeographical patterns; (4) the Himalayas and central and western China are the current centers of diversity of the ginseng genus; and (5) the low ITS sequence divergence and a close relationship among species in that region suggest that rapid evolutionary radiation may have created such a diversity of Panax in the Himalayas and in central and western China.

  Immunological aspects of Chinese medicinal plants as antiageing drugs.:J Ethnopharmacol. 1993 Mar;38(2-3):167-75. Review.Xiao PG, Xing ST, Wang LW. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS), Beijing.

 The development of a predominantly geriatric community worldwide has become an inevitable fact. Antiageing agents could be, in a certain sense, attentive to the well-being of the aged. There are quite a lot of medicinal plants and prescriptions recorded in Chinese medical literatures aimed at the well-being of the aged as well as the prevention of diseases and prolongation of life-span. By means of modern scientific research, a strategy towards antiageing drugs is presented in this paper. One of the effective routes is to select the candidates based on their ethnopharmacological usages, followed by immunological investigation in connection with other antiageing experimentation. A list of Chinese medicinal plants used as or related to the antiageing agents are presented. Specifically, five Chinese traditional drugs, Herba Epimedii, Fructus Lycii, Radix Polygoni multiflori, Radix Cynanchi auriculati and Ganoderma along with a composite prescription 'American Ginseng Royal Jelly' are selected as representatives. The prospect of research and development of antiageing drugs based on natural origin is also discussed.

  Preliminary study on soilless cultivation techniques of Panax quinquefolium L.:Zhongguo Zhong Yao Za Zhi. 1991 Sep;16(9):528-30, 574. Chinese.Chen Z, Ma X, Zho Y, Lu R, Song J.Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing.

 Our experiment has shown 1. Vermiculite with sand (volume 1:1) is a good substrate of soil for American Ginseng. The yield and contents of ginsenoside of American ginseng in this soilless substrate are a little higher than those in ordinary soil. 2. This kind of substrate can be used continuously with fewer occurrences of insect pest and plant diseases and contributes significantly to the reduction of production cost.

  American ginseng compound liquor on retarding-aging process.:Zhong Xi Yi Jie He Za Zhi. 1991 Aug;11(8):457-60, 451. Chinese.Cui J, Chen KJ.Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing.

 71 cases with age over sixty were randomly divided into treated group and control group, and observed by single-blind method. 36 cases were administered with American ginseng compound liquor as a treated group, 35 cases were administered with American ginseng liquor only as a control group. The total effective rates of the treated group and the control group on symptoms associated with aging were 88.89% and 68.57% respectively (P less than 0.05). The effective rates of the treated group for Kidney-Yang, Kidney-Qi and Kidney-Yin deficiencies were 85.71%, 100% and 87.50% respectively. The effective rates of the control group were 81.82%, 100% and 61.53% respectively. The above results indicated that the symptoms of Kidney-Yang deficiency in the treated group were improved much better than those of the control group (P less than 0.05). Obviously, SOD activity of erythrocyte and SOD/LPO ratio increased remarkably and serum content of LPO decreased significantly in both groups (P less than 0.001). In the treated group, the functional months of age (physiological age) decreased from 751.77 +/- 5.215 to 743.53 +/- 5.144, the effective rate was 68.57%. It showed that these two recipes both had the efficiency on prolonging the functional age (P less than 0.05).


  Processing technique of American ginseng.:Zhongguo Zhong Yao Za Zhi. 1990 Jul;15(7):408-11, 446. Chinese.Wang T, Jia Z, Liu C, Ren G.Institute of Special Wild Economic Animal and Plant Sciences, C.A.A.S. Jilinzuojia.

 The article deals with a new technique for processing American ginseng cultivated in China by far-infrared and moisture absorption. The qualities of processed product as per ton-quantity (including appearance, physical properties and chemical compositions) show no difference from those of American ginseng imported from U.S.A. and Canada. The mathematical model of dry-loss weight of American ginseng during processing is given in this article.

  Isolation and hypoglycemic activity of quinquefolans A, B, and C, glycans of Panax quinquefolium roots.:J Nat Prod. 1987 Mar-Apr;50(2):188-90.

 An H2O extract of the American crude drug "Amerika-ninjin" (American ginseng), Panax quinquefolium roots, exhibited significant hypoglycemic activity in mice. Activity-guided fractionation of the extract led to isolation of three glycans, quinquefolans A, B, and C, which displayed hypoglycemic effects in normal and alloxan-induced hyperglycemic mice.

  The physiological effects of Aralia, Panax and Eleutherococcus on exercised rats.:Jpn J Pharmacol. 1984 Jun;35(2):79-85.Martinez B, Staba EJ.

 Relative and total amount of saponins in Panax ginseng, Panax quinquefolius, Aralia mandshurica and Eleutherococcus senticosus were determined by thin-layer chromatography and by a spectrophotometric method. The ginsenoside Rg1 was present in American ginseng. Aralia and Eleutherococcus did not contain diol- and triol-type ginsenosides. Low concentrations of ginsenosides were found in Oriental red ginsengs (1.4-2.7%). Orally administered Araliaceae saponin extracts did not affect plasma lactic acid, glucagon, insulin or liver glycogen levels in exercised rats and did not prolong their swimming time. Plasma glucose levels in resting rats were decreased by saponin extracts of Canadian white, American red, Sanchi, Aralia, Eleutherococcus, Korean red and Shiu-Chi ginsengs.

  American ginseng. II. Analysis of ginsenosides and their sapogenins in biological fluids.:J Nat Prod. 1980 Jul-Aug;43(4):463-6.Chen SE, Staba EJ.

 A gas-liquid chromatography (tlc) method was developed to assay individual ginsenosides and sapogenins in rabbit plasma and urine samples. A flavonoid, panasenoside, and a sterol, stigmasterol, were used as internal standards for ginsenosides and their sapogenins, respectively. Linear relationships of peak height ratio to weight ratio were obtained for ginsenosides (A1, 20-350 microgram; A2, 20-400 microgram; B2, 20-300 microgram; C, 20-500 microgram), and sapogenins (panaxadiol or panaxatriol, 10-200 microgram) in 0.1 ml of the silylation mixture. The glc assay method developed was sensitive to 0.2 microgram of ginsenosides and 0.1 microgram of sapogenins.

  American ginseng. III. Pharmacokinetics of ginsenosides in the rabbit.:Eur J Drug Metab Pharmacokinet. 1980;5(3):161-8.Chen SE, Sawchuk RJ, Staba EJ.

 The pharmacokinetics of ginsenosides A1, A2, B2, and C were studied in rabbits and were best described with a one-component open model. Ginsenoside C (protopanaxadiol group ginseng saponin) showed a significantly longer half-life, higher plasma protein binding, and lower metabolic and renal clearance than ginsenosides A1, A2, and B2 (protopanaxatriol group ginseng saponins). All ginsenosides except ginsenoside A1 were slowly absorbed after intraperitoneal administration. Ginsenosides were not found in rabbit plasma or urine samples after oral administration. The observed differences in the pharmacokinetics of the ginsenosides may be ascribed to differences in protein binding. Ginsenoside C was more toxic than ginsenoside A2 after intraperitoneal administration to mice. Toxicity was not observed after oral administration of any of the ginsenosides. The genins, panaxadiol and panaxatriol, were more toxic and had larger volumes of distribution than the ginsenosides.


  Scientific References:

  1.Research Update:American Ginseng or Panax quinquefolius.