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Definition:Panax ginseng are majorly composed of
Chemical information disclosed as following table:
Research Update:Panax ginseng and Ginsenoside.
Neuroprotective effect of individual ginsenosides on astrocytes primary culture.:Biochim Biophys Acta. 2007 Jun 28;L¨®pez MV, Cuadrado MP, Ruiz-Poveda OM, Del Fresno AM, Accame ME.Department of Pharmacology, School of Pharmacy, Complutense University, Madrid, Spain.
Most of the known pharmacological effects of Panax ginseng on the central nervous system are due to its major components - ginsenosides. Although the antioxidant ability of ginseng root has already been established, this activity has never been evaluated for isolated ginsenosides on astrocytes. The activity of protopanaxadiols Rb(1), Rb(2), Rc and Rd, and protopanaxatriols Re and Rg(1) was evaluated in vitro on astrocytes primary culture by means of an oxidative stress model with H(2)O(2). The viability of astrocytes was determined by the MTT reduction assay and by the LDH release into the incubation medium. The effects on the antioxidant enzymes catalase, superoxide dismutase (SOD), glutathione peroxidases (GPx) and glutathione reductase (GR) and on the intracellular reactive oxygen species (ROS) formation were also investigated. Exposure of astrocytes to H(2)O(2) decreased cell viability as well as the antioxidant enzymes activity and increased ROS formation. Oxidative stress produced significant cell death that was reduced by previous treatment with the tested ginsenosides. Ginsenosides Rb(1), Rb(2), Re and Rg(1) were effective in reducing astrocytic death, while Rb(1), Rb(2), Rd, Re and Rg(1) decreased ROS formation, ginsenoside Re being the most active. Ginsenosides from P. ginseng induce neuroprotection mainly through activation of antioxidant enzymes.
Protective effects of ginsenoside Rb1, ginsenoside Rg1, and notoginsenoside R1 on lipopolysaccharide-induced microcirculatory disturbance in rat mesentery.:Life Sci. 2007 Jul 19;81(6):509-18. Epub 2007 Jun 28.Sun K, Wang CS, Guo J, Horie Y, Fang SP, Wang F, Liu YY, Liu LY, Yang JY, Fan JY, Han JY.Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China.
Ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1), and notoginsenoside R1 (R1) are major active components of Panax notoginseng, a Chinese herb that is widely used in traditional Chinese medicine to enhance blood circulation and dissipate blood stasis. To evaluate the effect of these saponins on microcirculatory disturbance induced by lipopolysaccharide (LPS), vascular hemodynamics in rat mesentery was observed continuously during their administration using an inverted microscope and a high speed video camera system. LPS administration decreased red blood cell velocity but Rb1, Rg1, and R1 attenuated this effect. LPS administration caused leukocyte adhesion to the venular wall, mast cell degranulation, and the release of cytokines. Rb1, Rg1, and R1 reduced the number of adherent leukocytes, and inhibited mast cell degranulation and cytokine elevation. In vitro experiments using flow cytometry further demonstrated that a) the LPS-enhanced expression of CD11b/CD18 by neutrophils was significantly depressed by Rb1 and R1, and b) hydrogen peroxide (H(2)O(2)) release from neutrophils in response to LPS stimulation was inhibited by treatment with Rg1 and R1. These results suggest that the protective effect of Rb1 and R1 against leukocyte adhesion elicited by LPS may be associated with their suppressive action on the expression of CD11b/CD18 by neutrophils. The protective effect against mast cell degranulation by Rb1 and R1, and the blunting of H(2)O(2) release from neutrophils by Rg1 and R1 suggest mechanistic diversity in the effects of Panax notoginseng saponins in the attenuation of microcirculatory disturbance induced by LPS
Vinegar-processed ginseng radix improves metabolic syndrome induced by a high fat diet in ICR mice.:Arch Pharm Res. 2007 May;30(5):587-95.Yun SN, Ko SK, Lee KH, Chung SH.College of Pharmacy, Kyung Hee University, Seoul 130-701, Korea.
Ginseng has made a successful transition from the world of traditional tonic remedies to conventional medicine, and since the 1920s ginseng root has been documented to be effective in diabetes, hypertension, dyslipidemia and obesity. Based on this wide spectrum of activity we wondered whether ginseng root extract might also be effective in metabolic syndrome (MetSyn). In a series of investigations to develop a potential anti-MetSyn agent, we prepared a vinegar-processed form of ginseng radix (ginsam, GS) and compared its anti-MetSyn effects to those of non-processed ginseng radix (GR) in an ICR mouse model of MetSyn induced by a high fat diet. GR- and GS-treated mice (500 mg/kg/day for 8 weeks) had an 81% and 90% decrease in insulin resistance respectively, compared to the high fat diet (HFD) control. White adipocyte size was dramatically reduced by 67% and 80% in GR- ahd GS-treated groups respectively, compared to the HFD fed control. This result was reflected by a marked inhibition of weight gain in GS-treated mice (GR vs. GS, 53% vs. 86%). Analysis of ginsenoside composition indicated that prosapogenin Rg3 might be responsible for the anti-MetSyn activity of GS. In conclusion, Vinegar-processed ginseng radix (GS) was found to have a significantly greater anti-MetSyn effect than ginseng radix, and we suggest that ginsam should be subjected to clinical trials in the future, and that the role of prosapogenin Rg3 in the anti-MetSyn effect of ginsam should be confirmed.
Combined effects of phytohormone, indole-3-butyric acid, and methyl jasmonate on root growth and ginsenoside production in adventitious root cultures of Panax ginseng C.A. Meyer.:Biotechnol Lett. 2007 Jul 4;Kim YS, Yeung EC, Hahn EJ, Paek KY.Research Center for the Development of Advanced Horticultural Technology, Chungbuk National University, Cheongju, Korea.
Indole-3-butyric acid at 25 muM with methyl jasmonate (MJ) at 100 muM in Panax ginseng synergistically stimulated both root growth and ginsenoside accumulation compared with 100 muM MJ alone. Productivity of ginsenoside was 10 mg l(-1) d(-1) compared to 7.3 mg l(-1) d(-1) with MJ elicitation alone.
Medicinal flowers. XVI. New dammarane-type triterpene tetraglycosides and gastroprotective principles from flower buds of Panax ginseng.:Chem Pharm Bull. 2007 Jul;55(7):1034-8.
The oligoglycoside fraction from the flower buds of Panax ginseng C. A. MEYER (Araliaceae) was found to show protective effects on ethanol-induced gastric mucosal lesions in rats. From the oligoglycoside fraction, new dammarane-type triterpene tetraglycosides, floralginsenosides M, N, O, and P, were isolated together with the major oligoglycosides ginsenoside Rd and Re. The structures of the new floralginsenosides were elucidated on the basis of chemical and physicochemical evidence. Ginsenoside Rd (protopanaxadiol 3,20-O-bisdesmoside) exhibited inhibitory effects on ethanol- and indomethacin-induced gastric mucosal lesions in rats.
Intravenous infusion of dihydroginsenoside Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL.:J Neurotrauma. 2007 Jun;24(6):1037-54.
Red ginseng root (Panax Ginseng CA Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of Red ginseng root is ginsenoside Rb(1) (gRb1). Previously, we showed that intravenous infusion of gRb1 ameliorated ischemic brain damage through upregulation of an anti-apoptotic factor, Bcl-x(L) and that topical application of gRb1 to burn wound lesion facilitated wound healing through upregulation of vascular endothelial growth factor (VEGF). In the present study, we produced dihydroginsenoside Rb1 (dgRb1), a stable chemical derivative of gRb1, and showed that intravenous infusion of dgRb1 improved spinal cord injury (SCI) as well as ischemic brain damage. As we expected, the effective dose of dgRb1 was ten times lower than that of gRb1. Intravenous infusion of dgRb1 at this effective dose did not affect brain temperature, blood pressure or cerebral blood flow, suggesting that dgRb1 rescued damaged neurons without affecting systemic parameters. In subsequent in vitro studies that focused on dgRb1-induced expression of gene products responsible for neuronal death or survival, we showed that dgRb1 could upregulate the expression of not only Bcl-x(L), but also a potent angiogenic and neurotrophic factor, VEGF. We also showed that dgRb1-induced expression of bcl-x(L) and VEGF mRNA was HRE (hypoxia response element) and STRE (signal transducers and activators of transcription 5 (Stat5) response element) dependent, respectively.
Experimental study on anti-platelet effects of ginsenoside -2A in vitro.:Zhongguo Zhong Xi Yi Jie He Za Zhi. 2006 Jun;26 Suppl:83-5. Chinese.Nie DN, Yin SM, Xie SF.Department of Hematology, The Second Hospital of Zhongshan University, Guangzhou (510120). niedanian@hotmail.com
OBJECTIVE: To explore the in vitro anti-platelet effects of Ginsenoside -2A,a purified extract from Panax notoginseng. METHODS: Platelet rich plasma (PRP) was prepared routinely from venous blood samples of patients with essential hypertension and normal persons. PRP was incubated with different concentrations of Nifedipine, Ginsenoside-2A ,and SK&F96365. Maximal platelet aggregation rate[ PAG (M) ] induced by 2 micromol/L ADP was taken as the observed index. Five-minute PAG( M) was determined for 5 consecutive times. RESULTS: (1) PAG (M) in essential hypertension group was 0. 89 +/- 0. 06, which was higher than that in the normal group (0. 68 +/-0. 07 ) with significant difference (P <0.01). (2)Nifedipine of two concentrations (10 p.mol/L,20 pVmol/L) had no effect on PAG(M) in either essential hypertension group or normal group(P >0. 05). (3)Different concentrations of SK&F96365 (2.5 micromol/L,5 micromol/L,10 micromol/L and 20 micromol/L) could inhibit the PAG(M) in essential hypertension group; (4) Differen concentrations of Ginsenoside -2A (2. 5 micromol/L, 5 micromol/L, 10 micromol/L and 20 micromol/L) could inhibit PAG ( M) in essential hypertension group; three concentrations of Ginsenoside -2A (5 micromol/L, 10 micromol/L, 20 micromol/L) could inhibit the PAG(M) in the normal group (all P <0.05). CONCLUSION: Platelet aggregating function in essential hypertension patients was obviously higher than that in the normal persons and platelets was in the high reactive status. Nifedipine had no inhibitive effect on platelet aggregation. SK&F96365 could inhibit the platelet aggregation. Ginsenoside-2A could inhibit platelet aggregation, and had the definite anti-platelet action.
Simultaneous quantification of 14 ginsenosides in Panax ginseng C.A. Meyer (Korean red ginseng) by HPLC-ELSD and its application to quality control.:J Pharm Biomed Anal. 2007 May 6;Kim SN, Ha YW, Shin H, Son SH, Wu SJ, Kim YS.Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-460, South Korea.
A new method of high-performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD) was developed for the simultaneous quantification of 14 major ginsenosides, which are the marker compounds of Panax ginseng C.A. Meyer (Korean red ginseng). Various types of ginseng samples were extracted, and the amounts of the 14 ginsenosides (Rg1, Re, Rf, Rh1, Rg2, Rb1, Rc, Rb2, Rb3, Rd, Rg3, Rk1, Rg5, and Rh2) were determined by reverse-phase HPLC-ELSD using digoxin as an internal standard. The mobile phase consisted of a programmed gradient of aqueous acetonitrile. Calibration curves for each ginsenoside were determined for the quantification. The method was validated for linearity, precision, accuracy, limit of detection, and limit of quantification. This quantification method was applied to several finished ginseng products including white ginseng, red ginseng powder, and red ginseng concentrate. The amounts of the 14 ginsenosides in the various ginseng samples could be analyzed simultaneously. This validated HPLC method is expected to provide a new basis for the quality assessment of ginseng products.
Ginsenosides compound K and Rh(2) inhibit tumor necrosis factor-alpha-induced activation of the NF-kappaB and JNK pathways in human astroglial cells.:Neurosci Lett. 2007 Jun 21;421(1):37-41. Epub 2007 May 22.Choi K, Kim M, Ryu J, Choi C.Laboratory of Computational Cell Biology, Department of Brain and Bioengineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
Ginsenosides, the main component of Panax ginseng, have been known for the anti-inflammatory and anti-proliferative activities. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory effects of ginsenosides on activated astroglial cells. Among 13 different ginsenosides, intestinal bacterial metabolites Rh(2) and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh(2) exert anti-inflammatory effects by the inhibition of both NF-kappaB and JNK pathways in a cell-specific manner.
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, 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.
Chemical characteristics of three medicinal plants of the Panax genus determined by HPLC-ELSD.:J Sep Sci. 2007 Apr;30(6):825-32.Wan JB, Li SP, Chen JM, Wang YT.Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China.
The morphological appearance and main ingredients of three Chinese medicines (CMs), P. ginseng, P. quinquefolius, and P. notoginseng of the Panax genus, are similar. However, their pharmacological activities are obviously different. To ensure their safety and efficacy, chemical characteristics of the three CMs were determined using pressurized liquid extraction and HPLC-evaporative light scattering detection. Twelve major saponins, namely notoginsenoside R1, pseudo-ginsenoside F11, ginsenosides Rg1, Re, Rf, Rb1, Rg2, Rc, Rb2, Rb3, Rd, and Rg3 were also quantitatively compared among the three CMs. The contents of total investigated saponins varied considerably, by up to 4-14-fold, between the highest (P. notoginseng, 82.8-136.5 mg/g) and the lowest values (P. ginseng, 10.0-21.1 mg/g). Hierarchical clustering analysis based on the characteristics of 11 investigated saponins (except ginsenoside Rb3) and notoginsenoside R1, pseudo-ginsenoside F11, and the ratio of ginsenoside Rg1/Rb1 and Rg1/Re showed that 56 tested samples were divided into three main clusters in accordance with the three Panax species. Similarity evaluation of chromatograms was also performed using "Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (Version 2004A)". The results showed that a high degree of similarity existed within individual clusters, but a low degree between the clusters, which could be used for quality control of the three CMs.
Ginsenoside Rh2 is one of the active principles of Panax ginseng root to improve insulin sensitivity in fructose-rich chow-fed rats.:Horm Metab Res. 2007 May;39(5):347-54.Lee WK, Kao ST, Liu IM, Cheng JT.Graduate School of Chinese Traditional Medicine, China Medical University, Taichung City, Taiwan, RO China.
Ginsenoside Rh2, one of the ginsenosides contained in the Panax ginseng root, was employed to screen the effect on insulin resistance of rats induced by a diet containing 60% fructose. Single intravenous injection of ginsenoside Rh2 decreased the plasma glucose concentrations in 60 minutes in a dose-dependent manner from 0.1 mg/kg to 1 mg/kg in rats with insulin resistance induced by fructose-rich chow. Repeated intravenous injection of ginsenoside Rh2 (1 mg/kg per injection, 3 times daily) into rats which received fructose-rich chow for 3 consecutive days decreased the value of glucose-insulin index, the product of the areas under the curve of glucose and insulin during the intraperitoneal (i.p.) glucose tolerance test. This means that ginsenoside Rh2 has an ability to improve insulin action on glucose disposal. The plasma glucose lowering action of tolbutamide, induced by the secretion of endogenous insulin, is widely used to characterize the formation of insulin resistance. Time for the loss of plasma glucose lowering response to tolbutamide (10 mg/kg, i.p.) in rats during insulin resistance induction by fructose-rich chow was also markedly delayed by the repeated treatment of ginsenoside Rh2, as compared to the vehicle-treated control. Thus, the repeated treatment of ginsenoside Rh2 delayed the development of insulin resistance in high fructose feeding rats. Increase of insulin sensitivity by ginsenoside Rh2 was further identified using the plasma glucose lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Repeated injection of ginsenoside Rh2 at the same dosing (1 mg/kg, 3 times daily) into STZ-diabetic rats for 10 days made an increase of the responses to exogenous insulin. Taken together, it can be concluded that ginsenoside Rh2 has an ability to improve insulin sensitivity and it seems suitable to use ginsenoside Rh2 as an adjuvant for diabetic patients and/or the subjects wishing to increase insulin sensitivity.
Induction of cyclooxygenase-2 by ginsenoside Rd via activation of CCAAT-enhancer binding proteins and cyclic AMP response binding protein.:Biochem Biophys Res Commun. 2007 Jul 20;359(1):51-6. Epub 2007 May 21.Jeong HG, Pokharel YR, Han EH, Kang KW.BK21 Project Team, College of Pharmacy, Chosun University, Seosuk-dong, Dong-gu, Gwangju 501-759, South Korea.
Panax ginseng is a widely used herbal medicine in East Asia and is reported to have a variety of pharmacological effects against cardiovascular diseases and cancers. Here we show a unique effect of ginsenoside Rd (Rd) on cyclooxygenase-2 (COX-2) expression in RAW264.7 macrophages. Rd (100 microg/ml), but not other ginsenosides induced COX-2 and increased prostaglandin E(2) production. Gel shift and Western blot analyses using nuclear fractions revealed that Rd increased both the DNA binding of and the nuclear levels of CCAAT/enhancer binding protein (C/EBP)alpha/beta and cyclic AMP response element binding protein (CREB), but not of p65, in RAW264.7 cells. Moreover, Rd increased the luciferase reporter gene activity in cells transfected with a 574-bp mouse COX-2 promoter construct. Site-specific mutation analyses confirmed that Rd-mediated transcriptional activation of COX-2 gene was regulated by C/EBP and CREB. These results provide evidence that Rd activated C/EBP and CREB, and that the activation of C/EBP and CREB appears to be essential for induction of COX-2 in RAW264.7 cells.
Eastern blotting and immunoaffinity concentration using monoclonal antibody for ginseng saponins in the field of traditional chinese medicines.:J Agric Food Chem. 2007 May 16;55(10):3783-7. Epub 2007 Apr 25.
Ginsenosides separated by silica gel TLC blotted to a PVDF membrane that was treated with a NaIO4 solution followed by bovine serum albumin (BSA) resulted in a ginsenoside-BSA conjugate on a PVDF membrane. The blotted spots were stained by anti-ginsenoside Rb1 (G-Rb1) and -Rg1 (G-Rg1) monoclonal antibodies (MAbs). The newly established immunostaining method, Eastern blotting, was applied for the determination of ginsenosides possessing protopanaxadiol and/or protopanaxatriol in the traditional Chinese medicine (TCM). This method developed a new way to separate the ginsenoside molecule into two functional parts using a simple and well-known chemical reaction. The sugar parts were oxidized by NaIO4 to give dialdehydes, which reacted with amino groups of the protein and covalently bound to the adsorbent PVDF membrane. The MAb bound to the aglycon part of the ginsenoside molecule for immunostaining. Double staining of Eastern blotting for ginsenosides using anti-G-Rb1 and -Rg1 MAbs promoted complete identification of ginsenosides in Panax species. The immunoaffinity concentration of G-Rb1 was deteremined by immunoaffinity column conjugated with anti-G-Rb1 MAb leading to the knock-out extract, which will be useful for the pharmacological investigation. To concentrate and determine G-Rb1 in P. japonicus, the crude extract of P. japonicus was fractionated by immunoaffinity column conjugated with anti-G-Rb1 MAb. Two ginsenosides, chikusetsusaponins III and IV having protopanaxadiol as an aglycon, were identified by Eastern blotting, although it was expected that G-Rb1 might be a component of P. japonicus by enzyme-linked immunosorbent assay (ELISA) analysis.
Effects of mRg2, a mixture of ginsenosides containing 60% Rg2, on the ultraviolet B-induced DNA repair synthesis and apoptosis in NIH3T3 cells.:Int J Toxicol. 2007 Mar-Apr;26(2):151-8.Jeong SJ, Han SH, Kim DY, Lee JC, Kim HS, Kim BH, Lee JS, Hwang EH, Park JK.Institute of Basic Natural Science, Wonkwang University, Iksan, Chonbuk, South Korea.
Ginseng has been used worldwidely as a traditional medicine of Asian countries for treatment of various diseases including cancer. The purpose of this study was to determine the effect of ginseng saponin mRg2, a mixture of ginsenosides containing 60% Rg2, on the repair and apoptosis of ultraviolet B (UVB)-exposed NIH3T3 cells. When cells were exposed to UVB and then incubated with normal growth medium for 48 h, cell viability, as determined by trypan blue exclusion assay decreased to about 25%. However, when mRg2 was included in the postincubation medium, the UVB-induced loss of cell viability was significantly reduced as compared with that postincubated in normal growth medium. 4,6-diamidino-2-phenylindole (DAPI) staining showed that postincubation of the UVB-exposed cells in medium containing mRg2 significantly reduced the apoptotic nuclear fragmentation. Interestingly, when cells were preincubated with mRg2 for 24 h and then exposed to various doses of UV, the amount of repair synthesis significantly increased as compared with those in cells exposed to UVB alone. Western blot analysis indicated that the mRg2 postincubation after UVB exposure potentiated the level of p53 and p21. The level of Triton nonextractable proliferating cell nuclear antigen (PCNA) also remained elevated by mRg2 postincubation. All these results suggest that mRg2 protects cells against UVB-induced genotoxicity by increasing DNA repair and decreasing apoptosis, in possible association with the modulation of protein levels involved in cell cycle arrest or progression.
Study on the hydroxyl radical scavenging activity changes of ginseng and ginsenoside-Rb2 by heat processing.:Biol Pharm Bull. 2007 Apr;30(4):724-8.
The free radical scavenging activities of Panax ginseng C.A. MEYER are known to increase by heat processing. Phenolic acids and Maillard reaction products (MRPs) have been suggested as active free radical scavenging components from our previous research, but heat processing-induced chemical and activity changes of ginsenosides considering the Maillard reaction have not yet been fully elucidated. In this study, we investigated the hydroxyl radical (.OH) scavenging activity changes of ginsengs and ginsenoside-Rb2 (Rb2)) by heat processing using an electron spin resonance spectrometer. Especially, Rb2 was heat processed with the same amount of glycine, a frequently used amino acid in the Maillard reaction model system. As a result, the .OH scavenging activities and brown compound levels of ginseng and glycine-Rb2 mixture were increased by heat processing. However, the increase in .OH scavenging activities were not in accordance with the extents of browning. On the other hand, less-polar ginsenosides such as Rg3, Rg5, and Rk1 were generated from the glycine-Rb2 mixture by heat processing. The sugar moieties at carbon-20 of Rb2 were separated by the steaming process, less-polar ginsenosides were produced, and then the separated sugar moieties were thought to form MRPs with glycine. From the .OH scavenging activity tests of Rb2, glycine, less-polar ginsenosides, and maltol, the increase in .OH scavenging activity was thought to be more closely related to the generation of .OH scavenging ginsenosides such as 20(S)-Rg3 and Rg5 by heat processing than MRPs.
Simultaneous determination of panax notoginsenoside R1, ginsenoside Rg1, Rd, Re and Rb1 in rat plasma by HPLC/ESI/MS: platform for the pharmacokinetic evaluation of total panax notoginsenoside, a typical kind of multiple constituent traditional Chinese medicine.:Biomed Chromatogr. 2007 Jul;21(7):735-46.Li X, Sun J, Wang G, Hao H, Liang Y, Zheng Y, Yan B, Sheng L.Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Box 210, 24# Tongjia Xiang Street, Nanjing 210009, People's Republic of China.
A platform for the pharmacokinetic study of multiple constituent traditional Chinese medicine was developed and validated. An HPLC/ESI/MS method was employed for the simultaneous determination of panax notoginsenoside R1, ginsenoside Rg1, Rd, Re and Rb1 in rat plasma. After the addition of digoxin as an internal standard (IS), rat plasmas were extracted with n-butanol saturated with pure water and all analytes were separated on a reversed-phased C(18) column with a mobile phase of acetonitrile-water (0.5 mM ammonium chloride) and pumped at a flow rate of 0.2 mL/min. Analytes were determined in a single quadrupole mass spectrometer using an electrospray ionization source. HPLC/ESI/MS was performed in the selected-ion monitoring mode with the chlorinated adducts of molecular ions [M + Cl]( -) at m/z 967.75, 835.80, 981.80, 981.80, 1143.65 and 815.40 for R1, Rg1, Rd, Re, Rb1 and digoxin, respectively. The method showed excellent linearity over the concentration range 3.03-775.00 ng/mL (r(2) = 0.9994) for R1, 4.00-1025.00 ng/mL (r(2) = 0.9991, 0.9988, 0.9991) for Rg1, Rd and Re, respectively, and 2.77-710.00 ng/mL for Rb1 (r(2) = 0.9990). The low limit of quantification was 3.03, 4.00, 4.00, 4.00 and 2.77 ng/mL for R1, Rg1, Rd, Re and Rb1, respectively, with S/N > 10. The intra- and inter-day precisions were below 12.00% and the accuracy was between -2.31 and +4.43% for all analytes. The extract recoveries of analytes were from 67.47 to 94.18%. All analytes were stable in rat plasma after storage for 12 h at ambient temperature, at 4 degrees C for 12 h in the sample pool, at -20 degrees C for 4 weeks and at -20 degrees C for three thaw-freeze cycles. The HPLC/ESI/MS technique provided an excellent method for the simultaneous quantification of R1, Rg1, Rd, Re and Rb1 in rat plasma and was successfully applied to the pharmacokinetic study of a multiple-constituent traditional Chinese medicine, total panax notoginsenoside (Xuesaitong injection).
Inhibitory effect of ginsenoside Rb1 on cardiac hypertrophy induced by monocrotaline in rat.:J Ethnopharmacol. 2007 May 22;111(3):567-72. Epub 2007 Jan 12.Jiang QS, Huang XN, Dai ZK, Yang GZ, Zhou QX, Shi JS, Wu Q.Chongqing Medical University, Department of Pharmacology, 400016 Chongqing, China.
Ginseng, the root of Panax ginseng, has been used as folk medicine in the treatment of various diseases for thousands of years in China. Ginsenoside Rb1 (Rb1), one of the effective components of ginseng, has been reported to release nitric oxide and decrease intracellular free Ca2+ in cardiac myocytes, both of which play important roles in antihypertrophic effect. This study was to investigate the potential effect of Rb1 on right ventricular hypertrophy (RVH) induced by monocrotaline (MCT) and its possible influence on calcineurin (CaN) signal trasnsduction pathway. MCT-treated animals were administered with Rb1 (10 and 40 mg /kg) from day 1 to day 14 (preventive administration) or from day 15 to day 28 (therapeutic administration), or with vehicle as corresponding controls. After 2 weeks, significantly hypertrophic reactions, including RVH index and the expressions of atrial natriuretic peptide mRNA, appeared in right ventricle of all MCT-treated animals (p < 0.05), which were significantly decreased with some improvements of myocardial pathomorphology in both Rb1 prevention- and therapy-groups (p < 0.05). Similarly, MCT-treatment caused the high expressions of mRNA and/or proteins of CaN, NFAT3 and GATA4 from cardiocytes (p < 0.05) and Rb1 could alleviate the expressions of these factors above (p < 0.05). These results suggest that Rb1 treatment can inhibit the RVH induced by MCT, which may be involved in its inhibitory effects on CaN signal transduction pathway.
Effect of sun ginseng methanol extract on lipopolysaccharide-induced liver injury in rats.:Phytomedicine. 2007 Mar 13;
Sun ginseng (SG) is heat-processed Panax ginseng C.A. Meyer steamed at 120 degrees C, which has ginsenoside-Rg(3), -Rk(1), and -Rg(5) as its main ginsenoside components. The effect of SG on lipopolysaccharide (LPS)-induced liver injury in rats was investigated in this study. Intravenous injection of LPS induced excessive nitric oxide ((.)NO) generation in serum and increased the hepatic mitochondrial thiobarbituric acid-reactive substance (TBA-RS) level. However, the elevated TBA-RS level was significantly lowered by 15 consecutive days of SG administrations. In addition, up-regulated hepatic inducible nitric oxide synthase and heme oxygenase 1 levels in LPS-treated control rats were significantly lowered and increased, respectively, by 100mg/kg body weight/day of SG administration. These antioxidant effects were thought to be partially related to the deactivation of nuclear factor-kappaB by SG administration.
The determination of contents of 8 ginsenosides in extraction of Panax ginseng by HPLC.:Zhong Yao Cai. 2006 Oct;29(10):1038-40. Chinese.Cao JL, Li ZL, Fu Q, Yan D, Liao QW, Xiao XH.Institute of Chinese Medicine, 302 Hospital of PLA, Beijing 100039, China. cj10506@sina.com
OBJECTIVE: To establish a method to determine the contents of 8 ginsenosides in extraction of Panax ginseng by HPLC. METHODS: The sample was analyzed on an ODS chromatogram column (Kromasil 250 mm x 4.6 mm, 5 microm), with mobile phase of acetonitrile-water (gradient elution) at flow rate 1.0 ml/min and detection at wavelength of 203 nm. RESULTS: RSD of stability, precision and recurrency was 0.55%-2.26%, 0.85%-1.93% and 0.97%-2.72% respectively. CONCLUSION: This method can be good for the content determination of ginsenoside.
Comparison of Qualitative and Quantitative in vitro Ginsenoside Production in Callus Cultures of Three Panax Species.:Planta Med. 1999 Jun;65(5):484-6.Mathur A, Mathur AK, Pal M, Uniyal GC.Divisions of Genetic Resources, Biotechnology, Medicinal Chemistry and Instrumentation, Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
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.
Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells.:J Ethnopharmacol. 2007 May 22;111(3):458-63. Epub 2006 Dec 20.Li N, Liu B, Dluzen DE, Jin Y.Department of Physiology, Medical College of Qingdao University, Qingdao 266071, PR China.
We investigated the effect of ginsenoside Rg2 on neurotoxic activities induced by glutamate in PC12 cells. The cells were incubated with glutamate (1 mmol/L), glutamate and ginsenoside Rg2 (0.05, 0.1, 0.2 mmol/L) or nimodipine (5 micromol/L) for 24 h. The cellular viability was assessed by MTT assay. The lipid peroxidation products malondialdehyde (MDA) and nitrogen oxide (NO) were measured by a spectrophotometric method. Fura-2/AM, as a cell permeable fluorescent probe for Ca2+, was used to detect intracellular Ca2+ concentration ([Ca2+]i) using a monespectrofluorometer. Immunocytochemical techniques were employed to check the protein expression levels of calpain II, caspase-3 and beta-amyloid (Abeta)1-40 in PC12 cells. The results showed that glutamate decreased the cell viability, increased [Ca2+]i, lipid peroxidation (the excessive production of MDA, NO) and the protein expression levels of calpain II, caspase-3 and Abeta1-40 in PC12 cells. Ginsenoside Rg2 significantly attenuated glutamate-induced neurotoxic effects upon these parameters at all doses tested. Our study suggests that ginsenoside Rg2 has a neuroprotective effect against glutamate-induced neurotoxicity through mechanisms related to anti-oxidation and anti-apoptosis. In addition, the inhibitory effect of ginsenoside Rg2 against the formation of Abeta1-40 suggests that ginsenoside Rg2 may also represent a potential treatment strategy for Alzheimer's disease.
Identification of ginsenoside interaction sites in 5-HT3A receptors.:Neuropharmacology. 2007 Mar;52(4):1139-50. Epub 2006 Dec 22.Lee BH, Lee JH, Lee SM, Jeong SM, Yoon IS, Lee JH, Choi SH, Pyo MK, Rhim H, Kim HC, Jang CG, Lee BC, Park CS, Nah SY.Ginsentology Research Laboratory, Department of Physiology, College of Veterinary Medicine, Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, South Korea.
We previously demonstrated that 20(S)-ginsenoside Rg(3) (Rg(3)), one of the active components of Panax ginseng, non-competitively inhibits 5-HT(3A) receptor channel activity on extracellular side of the cell. Here, we sought to elucidate the molecular mechanisms underlying Rg(3)-induced 5-HT(3A) receptor regulation. We used the two-microelectrode voltage-clamp technique to investigate the effect of Rg(3) on 5-HT-mediated ion currents (I(5-HT)) in Xenopus oocytes expressing wild-type or 5-HT(3A) receptors harboring mutations in the gating pore region of transmembrane domain 2 (TM2). In oocytes expressing wild-type 5-HT(3A) receptors, Rg(3) dose-dependently inhibited peak I(5-HT) with an IC(50) of 27.6+/-4.3microM. Mutations V291A, F292A, and I295A in TM2 greatly attenuated or abolished the Rg(3)-induced inhibition of peak I(5-HT). Mutation V291A but not F292A and I295A induced constitutively active ion currents with decrease of current decay rate. Rg(3) accelerated the rate of current decay with dose-dependent manner in the presence of 5-HT. Rg(3) and TMB-8, an open channel blocker, dose-dependently inhibited constitutively active ion currents. The IC(50) values of constitutively active ion currents in V291A mutant receptor were 72.4+/-23.1 and 6.5+/-0.7microM for Rg(3) and TMB-8, respectively. Diltiazem did not prevent Rg(3)-induced inhibition of constitutively active ion currents in occlusion experiments. These results indicate that Rg(3) inhibits 5-HT(3A) receptor channel activity through interactions with residues V291, F292, and I295 in the channel gating region of TM2 and further demonstrate that Rg(3) regulates 5-HT(3A) receptor channel activity in the open state at different site(s) from those of TMB-8 and diltiazem.
Neuroprotective effects of ginsenoside Rg3 against homocysteine-induced excitotoxicity in rat hippocampus.:Brain Res. 2007 Mar 9;1136(1):190-9. Epub 2006 Dec 22. Kim JH, Cho SY, Lee JH, Jeong SM, Yoon IS, Lee BH, Lee JH, Pyo MK, Lee SM, Chung JM, Kim S, Rhim H, Oh JW, Nah SY.Department of Physiology, College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea 561-756.
We previously demonstrated that ginsenoside Rg(3) (Rg(3)), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents and NMDA-induced neurotoxicity (Kim, S., Kim, T., Ahn, K., Park, W.K., Nah, S.Y., Rhim, H., 2004. Ginsenoside Rg(3) antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. Biochem. Biophys. Res. Commun. 323, 416-424). Accumulating evidence suggests that homocysteine (HC), a metabolite of methionine, exerts its excitotoxicity through NMDA receptor activation. In the present study, we examined the neuroprotective effects of Rg(3) on HC-induced hippocampal excitotoxicity in vitro and in vivo. Our in vitro studies using rat cultured hippocampal neurons revealed that Rg(3) treatment significantly and dose-dependently inhibited HC-induced hippocampal cell death, with an EC(50) value of 28.7+/-7.5 muM. Rg(3) treatment not only significantly reduced HC-induced DNA damage, but also dose-dependently attenuated HC-induced caspase-3 activity in vitro. Our in vivo studies revealed that intracerebroventricular (i.c.v.) pre-administration of Rg(3) significantly and dose-dependently reduced i.c.v. HC-induced hippocampal damage in rats. To examine the mechanisms underlying the in vitro and in vivo neuroprotective effects of Rg(3) against HC-induced hippocampal excitotoxicity, we examined the effect of Rg(3) on HC-induced intracellular Ca(2+) elevations in cultured hippocampal cells and found that Rg(3) treatment dose-dependently inhibited HC-induced intracellular Ca(2+) elevation, with an IC(50) value of 41.5+/-17.5 muM. In addition, Rg(3) treatment dose-dependently inhibited HC-induced currents in Xenopus oocytes expressing the NMDA receptor, with an IC(50) of 47.3+/-14.2 muM. These results collectively indicate that Rg(3)-induced neuroprotection against HC in rat hippocampus might be achieved via inhibition of HC-mediated NMDA receptor activation.
Effect of 17beta-oestradiol and ginsenoside on osteoporosis in ovariectomised rats.:J Asian Nat Prod Res. 2006 Oct-Nov;8(7):649-56.Gong YS, Chen J, Zhang QZ, Zhang JT.Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
To study the anti-osteoporosis effects and mechanism of action of oestradiol (E2) and ginsenoside (tR), we measured the bone mineral densities (BMD) of lumbar vertebra and tibia and analysed the tibia histological morphological data, as well observed the activity and the number of osteoblasts and the activity of alkaline phosphatase (ALP) and the concentration of cAMP. Results showed that E2 (400 microg kg- 1 week- 1) and tR (10, 20, 30 mg kg- 1 day- 1) were able to countervail the decreasing in BMDs of lumbar vertebra and tibia induced by OVX in rats (P<0.05); E2 (0.1 micromol l- 1) and ginsenoside Rg1 (1 micromol l- 1 and 10 micromol l- 1) were able to increase the number of osteoblasts, the activity of ALP and the concentration of intercellular cAMP in cultured osteoblast cells. The present findings suggest that E2 and tR have an anti-osteoporosis effect in ovariectomised rats.
Ginsenoside Rb1 promotes adipogenesis in 3T3-L1 cells by enhancing PPARgamma2 and C/EBPalpha gene expression.:Life Sci. 2007 Jan 23;80(7):618-25. Epub 2006 Nov 28.Shang W, Yang Y, Jiang B, Jin H, Zhou L, Liu S, Chen M.Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, 197 Ruijin Road II, Shanghai 200025, China.
Evidence has accumulated that ginseng and its main active constituents, ginsenosides, possess anti-diabetic and insulin-sensitizing properties which may be partly realized by regulating adipocyte development and functions. In the present study, we explored the effect of ginsenoside Rb(1), the most abundant ginsenoside in ginseng root, on adipogenesis of 3T3-L1 cells. We found that with standard differentiation inducers, ginsenoside Rb(1) facilitated adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner; 10 microM Rb(1) increased lipid accumulation by about 56%. Treatment of differentiating adipocytes with 10 microM Rb(1) increased the expression of mRNA and protein of PPARgamma(2) and C/EBPalpha, as well as mRNA of ap2, one of their target genes. After the treatment of differentiating adipocytes with Rb(1), basal and insulin-mediated glucose uptake was significantly augmented, accompanied by the up-regulation of mRNA and protein level of GLUT4, but not of GLUT1. In addition, ginsenoside Rb(1) also inhibited the proliferation of preconfluent 3T3-L1 preadipocytes. Our data indicate that anti-diabetic and insulin-sensitizing activities of ginsenosides, at least in part, are involved in the enhancing effect on PPARgamma2 and C/EBPalpha expression, hence promoting adipogenesis.
Determination of notoginsenoside R1 and ginsenoside Rg1 in Rupixiao tablets by HPLC:Zhongguo Zhong Yao Za Zhi. 2006 Jul;31(13):1067-9. Chinese.Xu GB, Wang ZT, Pan N, Zhao Z.China Pharmaceutical University, Nanjing.
OBJECTIVE: To determine the content of notoginsenoside R1 and ginsenoside Rg1 in Rupixiao tablet by reverse-phase high performance liquid chromatography. METHOD: A Kromacil C18 column was used with a mixture of acetonitrile and 0.05% phosphoric acid solution (20:80) as the mobile phase at a flow rate of 1.2 mL x min(-1) with the detection wavelength at 203 nm. RESULT: The measurement proved to be linear over the range of 0.941-9.41 g for notoginsenoside R1 and 1.04-10.4 g for ginsenoside Rg1. The average recovery of this method was 97.3% and 97.9% respectively. CONCLUSION: The method was simple, reliable, and accurate and can be used for the quality control of this preparation.
Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats.:Eur J Pharmacol. 2006 Nov 21;550(1-3):173-9. Epub 2006 Sep 8.Cho WC, Chung WS, Lee SK, Leung AW, Cheng CH, Yue KK.School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Hong Kong, China. williamcscho@gmail.com
Diabetes mellitus is characterized by hyperglycemia and complications affecting the eye, kidney, nerve and blood vessel. We have previously demonstrated the occurrence of oxidative stress of streptozotocin-induced diabetic rats, preceded by a depletion in the tissue level of glutathione. In this study, when diabetic rats were treated with ginsenoside Re of Panax ginseng C.A. Meyer, there was a significant reduction in blood glucose, total cholesterol and triglyceride levels. On the other hand, oxidative stress has been implicated in the pathogenesis of diabetes and its complications. It was found that treatment by ginsenoside Re restored the levels of both glutathione and malondialdehyde in the eye and kidney to those found in the control rats. This is the first report demonstrating ginsenoside Re has significant antioxidant efficacy in diabetes, and prevents the onset of oxidative stress in some vascular tissues. Our results demonstrated that ginsenoside Re could lower blood glucose and lipid levels, and exerts protective actions against the occurrence of oxidative stress in the eye and kidney of diabetic rats. Our data also provide evidence that ginsenoside Re could be used as an effective antidiabetic agent particularly in the prevention of diabetic microvasculopathy.
Analysis of ginsenosides in Sheng-Mai-Yin decoction by high performance liquid chromatography-diode array detection-electrospray mass spectrometry.:Se Pu. 2006 Jul;24(4):325-30. Chinese.Wang Z, Wang H, Chen S.Research Laboratory of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
A method of high performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD/MS) in negative ion mode was developed for the analysis of ginsenosides in Sheng-Mai-Yin decoction (Panax gingeng C. A. Mey, Ophiopogon japonicus (Thunb.) Ker-Gawl, Shisandra chinensis (Turcz.) Baill.). The analyses were preformed on a reversed-phase C18 column (4.6 mm i.d. x 150 mm, 5 microm) using a binary eluent (10 mmol/L ammonium acetate (A) and acetonitrile (B), 1 mL/min) under gradient conditions (60% A - 40% A at 0 - 30 min, 40% A - 30% A at 30 - 40 min). Seventeen ginsenosides (20 (R) -Rh1, Rh2, Rg3, Rg2; 20 (S) -Rh1, Rh2, Rg3, Rg2; Rf, Rg6, Rg5, F4, Rk1, Rk3, Rh4; 20 (S)- and 20 (R) -protopanaxatriol) were well separated and detected at 203 nm by a DAD detector. The effluent from the DAD detector was introduced into the electrospray ionization (ESI) source in a post-column splitting flow rate at 0.3 mL/min. In the mass spectrum two major ions [M - H]- and [M + AcO]- were observed for ginsenoside standards (20 (R) -Rh1, Rg3, Rh2; 20 (S) -Rh1, Rg3, Rh2; 20 (S)- and 20 (R) -protopanaxatriol) and ginsenosides in Sheng-Mai-Yin decoction. Some other ions [M - Glc - H]-, [M - 2Glc - H]-, [M - Rha - H- and [M - Rha - Glc - H]- were also found in the mass spectrum of ginsenosides of Sheng-Mai-Yin decoction. In the decoction process ginsenosides changed into constituents of moderate and low polarity by hydrolysis, isomerization and dehydration at the site of C-20 and hydrolysis reaction also occurred at the site of C-3 or C-6. The work above presents a quick and accurate assay method which can could be used for the qualitative analysis of ginsenosides in Sheng-Mai-Yin decoction and the quality control of Sheng-Mai-Yin preparation.
Ginsenoside Re, a main phytosterol of Panax ginseng, activates cardiac potassium channels via a nongenomic pathway of sex hormones.:Mol Pharmacol. 2006 Dec;70(6):1916-24. Epub 2006 Sep 19.
Ginseng root is one of the most popular herbs throughout the world and is believed to be a panacea and to promote longevity. It has been used as a medicine to protect against cardiac ischemia, a major cause of death in the West. We have previously demonstrated that ginsenoside Re, a main phytosterol of Panax ginseng, inhibits Ca(2+) accumulation in mitochondria during cardiac ischemia/reperfusion, which is attributable to nitric oxide (NO)-induced Ca(2+) channel inhibition and K(+) channel activation in cardiac myocytes. In this study, we provide compelling evidence that ginsenoside Re activates endothelial NO synthase (eNOS) to release NO, resulting in activation of the slowly activating delayed rectifier K(+) current. The eNOS activation occurs via a nongenomic pathway of each of androgen receptor, estrogen receptor-alpha, and progesterone receptor, in which c-Src, phosphoinositide 3-kinase, Akt, and eNOS are sequentially activated. However, ginsenoside Re does not stimulate proliferation of androgen-responsive LNCaP cells and estrogen-responsive MCF-7 cells, implying that ginsenoside Re does not activate a genomic pathway of sex hormone receptors. Fluorescence resonance energy transfer experiments with a probe, SCCoR (single cell coactivator recruitment), indicate that the lack of genomic action is attributable to failure of coactivator recruitment. Thus, ginsenoside Re acts as a specific agonist for the nongenomic pathway of sex steroid receptors, and NO released from activated eNOS underlies cardiac K(+) channel activation and protection against ischemia-reperfusion injury.
Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax ginseng: in vitro and in vivo studies.:Int J Pharm. 2007 Jan 10;328(2):168-76. Epub 2006 Aug 18.Yu LC, Chen SC, Chang WC, Huang YC, Lin KM, Lai PH, Sung HW.Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
The study was designed to investigate the stability of ginsenoside Rg(1) (Rg(1)) and Re (Re), two natural herbal compounds isolated from Panax ginseng, based on their activity to promote angiogenesis in vitro and in vivo. After being treated at different temperatures, pHs, and solvent species for distinct durations, the remaining activities of Rg(1) and Re on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation were examined in vitro. Additionally, the remaining activity of each treated test agent, mixed in a growth factor-reduced Matrigel, in stimulating angiogenesis was evaluated subcutaneously in a mouse model. Basic fibroblast growth factor (bFGF) was used as a control. It was found in vitro that HUVEC proliferation, migration in a Transwell plate, and tube formation on Matrigel were all significantly enhanced in the presence of bFGF, Rg(1), or Re. However, after being treated at different temperatures, pHs, or solvent species, the remaining activity of bFGF on HUVEC behaviors reduced significantly. This observation was more significant with increasing the duration of treatment. In contrast, the activities of Rg(1) and Re remained unchanged throughout the entire course of the study. The in vivo results observed on day 7 after implantation showed that the blank control (Matrigel alone) was slightly vascularized. In contrast, the density of neo-vessels in the Matrigel plug mixed with bFGF, Rg(1), or Re was significantly enhanced. However, after being treated, the density of neo-vessels was significantly reduced in the Matrigel plug mixed with bFGF, while those of Rg(1) and Re remained unchanged. The aforementioned results suggested that Rg(1) and Re could be a novel group of nonpeptide angiogenic agents with a superior stability and may be used for the management of tissue regeneration.
Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng.:FEBS Lett. 2006 Oct 2;580(22):5143-9. Epub 2006 Sep 1.
Panax ginseng produces triterpene saponins called ginsenosides, which are classified into two groups by the skeleton of aglycones, namely dammarane type and oleanane type. Dammarane-type ginsenosides dominate over oleanane type not only in amount but also in structural varieties. However, their sapogenin structure is restricted to two aglycones, protopanaxadiol and protopanaxatriol. So far, the genes encoding oxidosqualene cyclase (OSC) responsible for formation of dammarane skeleton have not been cloned, although OSC yielding oleanane skeleton (beta-amyrin synthase) has been successfully cloned from this plant. In this study, cDNA cloning of OSC producing dammmarane triterpene was attempted from hairy root cultures of P. ginseng by homology based PCR method. A new OSC gene (named as PNA) obtained was expressed in a lanosterol synthase deficient (erg7) Saccharomyces cerevisiae strain GIL77. LC-MS and NMR analyses identified the accumulated product in the yeast transformant to be dammarenediol-II, demonstrating PNA to encode dammarenediol-II synthase.
20(S)-Ginsenoside Rg3 prevents endothelial cell apoptosis via inhibition of a mitochondrial caspase pathway.:Biochem Biophys Res Commun. 2006 Oct 27;349(3):987-94. Epub 2006 Aug 30.
Studies on the preparation, crystal structure and bioactivity of ginsenoside compound K.:J Asian Nat Prod Res. 2006 Sep;8(6):519-27.Zhou W, Feng MQ, Li JY, Zhou P.Department of Biosynthetic Drugs, School of Pharmacy, Fudan University, 138 YiXueYuan Road, Shanghai 200032, China.
Microbial transformation of Panaxnotoginseng saponins (PNS) using Aspergillus niger afforded, as the main metabolite, ginsenoside compound K (20-O-beta-glucopyranosyl-20(S)-protopanaxadiol). Its structure was determined spectroscopically and by X-ray analysis, and this is the first time the crystal structure of ginsenoside has been reported. In comparison with ginsenoside Rb1, the pro-drug for this metabolite, compound K exhibits potent cytotoxic activity against tumor cell lines. The mean concentrations of compound K needed to inhibit the proliferation of cells by 50% (IC50) were 12.7, 11.4, 8.5 and 9.7 microM for mouse high-metastatic melanoma (B16-BL6), human hepatoma (HepG2), human myeloid leukemia (K562) and human high-metastatic lung carcinoma (95-D) cell lines, respectively. The data show that ginsenoside compound K is a good antitumor drug candidate.
In vitro anti-cancer activity and structure-activity relationships of natural products isolated from fruits of Panax ginseng.:Cancer Chemother Pharmacol. 2007 Apr;59(5):589-601. Epub 2006 Aug 22.Wang W, Zhao Y, Rayburn ER, Hill DL, Wang H, Zhang R.Department of Pharmacology and Toxicology, Division of Clinical Pharmacology, Cancer Pharmacology Laboratory, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
PURPOSE: Panax ginseng and its extracts have long been used for medical purposes; there is increasing interest in developing ginseng products as cancer preventive or therapeutic agents. The present study was designed to determine biological structure-activity relationships (SAR) for saponins present in Panax ginseng fruits. METHODS: Eleven saponins were extracted from P. ginseng fruits and purified by use of D(101) resin and ordinary and reverse-phase silica gel column chromatography. Their chemical structures were elucidated on the basis of physicochemical constants and NMR spectra. Compounds were then evaluated for SAR with their in vitro cytotoxicity against several human cancer cell lines. RESULTS: The 11 compounds were identified as 20(R)-dammarane-3beta,12beta,20,25-tetrol (25-OH-PPD, 1); 20(R)-dammarane-3beta,6alpha,12beta,20,25-pentol (25-OH-PPT, 2); 20(S)-protopanaxadiol (PPD, 3); daucosterine 4, 20(S)-ginsenoside-Rh(2) (Rh(2), 5); 20(S)-ginsenoside-Rg(3) (Rg(3,) 6); 20(S)-ginsenoside-Rg(2) (Rg(2), 7); 20(S)-ginsenoside-Rg(1) (Rg(1), 8); 20(S)-ginsenoside-Rd (Rd, 9); 20(S)-ginsenoside-Re (Re, 10); and 20(S)-ginsenoside-Rb(1) (Rb(1), 11). Among the eleven compounds, 1, 3 and 5 were the most effective inhibitors of cell growth and proliferation and inducers of apoptosis and cell cycle arrest. For 1, the IC(50) values for most cell lines were in the range of 10-60 microM, at least twofold lower than for any of the other compounds. Compounds 1 and 3 had significant, dose-dependent effects on apoptosis, proliferation, and cell cycle progression. CONCLUSIONS: The results suggest that the type of dammarane, the number of sugar moieties, and differences in the substituent groups affect their anti-cancer activity. This information may be useful for evaluating the structure/function relationship of other ginsenosides and their aglycones and for development of novel anticancer agents.
Ginsenoside Rb1 promotes neurotransmitter release by modulating phosphorylation of synapsins through a cAMP-dependent protein kinase pathway.:Brain Res. 2006 Aug 23;1106(1):91-8. Epub 2006 Jul 11.Xue JF, Liu ZJ, Hu JF, Chen H, Zhang JT, Chen NH.Institute of Material Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), has been extensively used in traditional oriental medicine for the prevention and treatment of aging-related disorders for over 2000 years. Accumulating evidence suggests that ginsenosides such as Rg1 and Rb1, which are the pharmacologically active ingredients of ginseng, modulate neurotransmission. Synapsins are abundant phosphoproteins essential for regulating neurotransmitter release. All synapsins contain a short amino-terminal domain A that is highly conserved and phosphorylated by cAMP-dependent protein kinase (PKA), which plays a key role in regulating neurotransmitter release. In the present study, we demonstrated that both Rg1 and Rb1 increased neurotransmitter release in undifferentiated and differentiated PC12 cells. However, in the presence of the PKA inhibitor H89, Rg1, but not Rb1, still induced neurotransmitter release. Moreover, Rb1, but not Rg1, enhanced the phosphorylation of synapsins via PKA pathway. In summary, Rb1 promotes neurotransmitter release by increasing the phosphorylation of synapsins through the PKA pathway, whereas the similar effects observed with Rg1 are independent of the phosphorylation of synapsins.
Reductions in levels of the Alzheimer's amyloid beta peptide after oral administration of ginsenosides.:FASEB J. 2006 Jun;20(8):1269-71. Epub 2006 Apr 24.Chen F, Eckman EA, Eckman CB.Mayo Clinic College of Medicine, Department of Pharmacology, Birdsall Bldg. Rm. 327, 4500 San Pablo Rd., Jacksonville, Florida 32224, USA.
For millennia, ginseng and some of its components have been used to treat a wide variety of medical conditions, including age-related memory impairment. Because of its purported effects and apparently low rate of side effects, ginseng remains one of the top selling natural product remedies in the United States. Given its potential role for improving age-related memory impairments and its common use in China for the treatment of Alzheimer's disease-like symptoms, we analyzed the effects of commercially available preparations of ginseng on the accumulation of the Alzheimer's amyloid beta peptide (Abeta) in a cell-based model system. In this model system, ginseng treatment resulted in a significant reduction in the levels of Abeta in the conditioned medium. We next examined the effects of several compounds isolated from ginseng and found that certain ginsenosides lowered Abeta concentration in a dose-dependent manner with ginsenoside Rg3 having an approximate IC50 of under 25 microM against Abeta42. Furthermore, we found that three of these isolated components, ginsenoside Rg1, Rg3, and RE, resulted in significant reductions in the amount of Abeta detected in the brains of animals after single oral doses of these agents. The results indicate that ginseng itself, or purified ginsenosides, may have similarly useful effects in human disease.
Ginsenoside Rh(2) enhances antitumour activity and decreases genotoxic effect of cyclophosphamide.:Basic Clin Pharmacol Toxicol. 2006 Apr;98(4):411-5.Wang Z, Zheng Q, Liu K, Li G, Zheng R.School of Life Sciences, Lanzhou University, Lanzhou, People's Republic of China.
Ginsenoside Rh(2), a panaxadiol saponins, possesses various antitumour properties. Cyclophosphamide, an alkylating agent, has been shown to possess various genotoxic and carcinogenic effects, however, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. Previous reports reveal that cyclophosphamide is involved in some secondary neoplasms. In this study, the antitumour activity and genotoxic effect of oral intake of ginsenoside Rh(2) combined with intraperitoneal injection of cyclophosphamide was investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung carcinoma cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis as well. The results indicated that oral administration of Rh(2) (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while Rh(2) synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. Rh(2) decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggest that ginsenoside Rh(2) is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.
In Vivo radioprotective effect of Panax ginseng C.A. Meyer and identification of active ginsenosides.:Phytother Res. 2006 May;20(5):392-5.Lee HJ, Kim SR, Kim JC, Kang CM, Lee YS, Jo SK, Kim TH, Jang JS, Nah SY, Kim SH.College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea.
This study evaluated the effect of water extracts of Panax ginseng C.A. Meyer (PG), panaxadiol (PD), panaxatriol (PT), ginsenoside Rb(1), Rb(2), Rc, Rd, Re and Rg(1) on jejunal crypt survival, endogenous spleen colony formation and apoptosis in jejunal crypt cells in gamma-irradiated mice. Jejunal crypts were protected by pretreatment with PG, Rc and Rd. Administration of PG, PD, Rd and Re prior to irradiation resulted in an increase in the formation of endogenous spleen colonies. The frequency of radiation-induced apoptosis in intestinal crypt cells was also reduced by pretreatment with PG, PD, Rb(2), Rc, Rd, Re and Rg(1). In experiments on the effects of the individual ginsenosides, the rank order of activity was Rc > Rd > Rg(1) > Rb(2) > Re > Rb(1) on intestinal crypt survival assay, Re > Rb(2) > Rd > Rg(1) > Rb(1) > Rc on the spleen colony formation assay, and Rg(1) > Re > Rd > Rc > Rb(2) > Rb(1) on inhibiting the death of cells caused by apoptosis. The results indicated that Rc, Rd and Re may have a major radioprotective effect in mice irradiated with high and low doses of radiation. When the same experiments were performed using PD and PT, it was observed that most of the inhibitory effects came from PD rather than PT.
Chemical investigation on Sijunzi decoction and its two major herbs Panax ginseng and Glycyrrhiza uralensis by LC/MS/MS.:J Pharm Biomed Anal. 2006 Aug 28;41(5):1642-7. Epub 2006 Mar 29.Liu Y, Yang J, Cai Z.Peking Union Medical College, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100094, China.
Sijunzi decoction consists of Panax ginseng, Poria cocos, Atractylodes macrocephala and Glycyrrhiza uralensis. High performance liquid chromatography coupled with tandem mass spectrometry (LC/MS(n)) was applied to identify and characterize three types of active components, ginsenoside (from P. ginseng), flavonoid and triterpenoid (from G. uralensis) in Sijunzi decoction. Spectra of MS and MS/MS from [M+Na](+) ions of ginsenosides were acquired and interpreted for their identification. Fragmentations with losing masses of 194 or 176Da were the characteristic ions of triterpenoids in the MS/MS analysis. A characteristic fragment ion of the aglycon moiety at m/z 257 from source collision-induced dissociation was observed for flavonoid. LC/MS was also applied for the comparison of relative peak area of major active components between Sijunzi decoction and the single herb extracts. The concentration ratios of major active components detected in the individual herbs of P. ginseng and G. uralensis were found different from those in Sijunzi decoction. The experimental data indicated that the decocting process could result in the difference in the amount of active components.
20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons.:Eur J Pharmacol. 2006 Apr 24;536(1-2):69-77. Epub 2006 Feb 28.Lee E, Kim S, Chung KC, Choo MK, Kim DH, Nam G, Rhim H.Biomedical Research Center, Korea Institute of Science and Technology (KIST), 39-1 Hawholgok-dong Sungbuk-gu, Seoul 136-791, Republic of Korea.
Most herbal medicines that are orally administrated have been known to be metabolized before they are absorbed from the gastrointestinal tract. We, therefore, examined the effects of 20(S)-ginsenosides Rb1, Rg1 and Rg3, the three most commonly studied ginsenosides in the central nervous system, and their main metabolites on NMDA receptors using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques. Among the nine ginsenosides tested, 20(S)-ginsenoside Rh2 (20(S)-Rh2) along with 20(S)-ginsenoside Rg3 (20(S)-Rg3) produced the highest inhibitory effect in cultured hippocampal neurons. Although 20(S)-Rg3 and 20(S)-Rh2 selectively targeted NMDA receptors with similar potency, they produced additive effects and seemed to modulate different NMDA receptor regulatory sites. As a competitive antagonist, 20(S)-Rh2 seems to inhibit the receptor via its interaction with polyamine-binding sites, and 20(S)-Rg3 does so using glycine-binding sites. Therefore, these results suggest that the treatment of 20(S)-Rh2, a newly identified active ingredient of ginseng, might be a novel preventive candidate in treating neurodegenerative disorders.
The effects of ginsenoside Re and its metabolite, ginsenoside Rh1, on 12-O-tetradecanoylphorbol 13-acetate- and oxazolone-induced mouse dermatitis models.:Planta Med. 2006 Mar;72(4):376-8.Shin YW, Bae EA, Kim SS, Lee YC, Lee BY, Kim DH.College of Pharmacy, Kyung Hee University, Seoul, Korea.
The effects of the main constituent ginsenoside Re in ginseng and its metabolite, ginsenoside Rh1, were investigated in 12-O-tetradecanoylphorbol 13-acetate (TPA)- and oxazolone-induced mouse ear dermatitis models. Ginsenoside Rh1 potently suppressed the TPA- and oxazolone-induced swellings as well as mRNA expression levels of cyclooxygenase-2, IL-1beta and TNF-alpha, although these were only weakly inhibited by ginsenoside Re.
Oral absorption of ginsenoside Rb1 using in vitro and in vivo models:Planta Med. 2006 Apr;72(5):398-404.Han M, Sha X, Wu Y, Fang X.Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
This research attempts to clarify the cause for poor oral absorption of ginsenoside Rb1 (Rb1), one main ingredient of the well known Panax notoginseng saponins (PNS) for curing hemorrhage. Caco-2 cell monolayers were used as an in vitro model to reveal the transport mechanism of Rb1 across the intestinal mucosa. Moreover, the serum concentration-time profiles of Rb1 after tail venous (IV), portal venous (PV), intraduodenal (ID) and peroral (PO) administration to rats were compared to evaluate the first-pass effects of stomach, intestine and liver. In vitro experiments showed that uptake by Caco-2 cell monolayers was temperature dependent, but was not influenced by cyclosporine A and ketoconazole. The change in the apical pH showed no obvious effects on the uptake of Rb1. The uptake and transport were non-saturable, and flux from the apical compartment to the basolateral compartment (A-B) increased linearly with increasing concentration, which indicated a passive transport. Meanwhile, an apparent permeability coefficient of (5.90 +/- 1.02) x 10(-8) cm/s (C0 = 1 mg/mL) predicted an incomplete absorption. The investigation on the pharmacokinetic behavior of Rb1 after different routes of administration to rats showed a significant difference between PO (F(PO) was 0.64%), ID (F(ID) was 2.46%) and PV (F(PV) was 59.49%) administration, and the first-pass effect of the intestine is more significant than that of the stomach and liver in the absorption process. In summary, elimination in the stomach, large intestine and liver contributed to the poor absorption of Rb1, but the low membrane permeability might be a more important factor dominating the extent of absorption.
The antistress effect of ginseng total saponin and ginsenoside Rg3 and Rb1 evaluated by brain polyamine level under immobilization stress.:Pharmacol Res. 2006 Jul;54(1):46-9. Epub 2006 Mar 10.Lee SH, Jung BH, Kim SY, Lee EH, Chung BC.Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, South Korea.
The present study aims to demonstrate the ability of ginseng total saponin (GTS), ginsenosides Rg3 and Rb1 to reduce brain polyamine levels in immobilization-stressed gerbil mice. A previous study reported that ginsenosides had an anti-stress property. So, we tested the anti-stress effect of ginseng by investigating the brain level of polyamine, a well-known stress stimuli marker. We determined the brain polyamine levels under 30-min immobilization stress in pretreating GTS (100 mgkg(-1), oral), ginsenosides Rg3 and Rb1 (10 mgkg(-1), oral, respectively). Then, we compared polyamine levels between the non-stressed mouse and the stressed mouse which had taken saline orally to check the placebo effect. Putrescine (PUT) levels were significantly increased (P < 0.01) in the stressed condition, but it was reduced in pretreatment of GTS, ginsenosides Rg3 (P < 0.01, respectively) and Rb1 (P < 0.001) under 30-min immobilization stressed-mouse. However, other polyamine levels did not change regardless of stressed condition or GTS-, ginsenosides Rg3- and Rb1-treated stressed condition. These results mean that only PUT could be a marker for stress and GTS, ginsenosides Rg3 and Rb1 administration lead to an anti-stress effect. Thus, our studies indicate that GTS, ginsenosides Rg3 and Rb1 may play a neuroprotective role in the immobilization-stressed brain.
Mediation of beta-endorphin by ginsenoside Rh2 to lower plasma glucose in streptozotocin-induced diabetic rats.:Planta Med. 2006 Jan;72(1):9-13.Lai DM, Tu YK, Liu IM, Chen PF, Cheng JT.Neurosurgical Division, Department of Surgery, National Taiwan University Hospital, Taipei City, Taiwan, R.O.C.
We investigated the plasma glucose-lowering mechanism(s) of Rh2, a ginsenoside derived from Panax ginseng, in rats with streptozotocin-induced diabetes (STZ-diabetic rats). After intravenous injection over 120 min into fasting STZ-diabetic rats, Rh2 decreased plasma glucose in a dose-dependent manner. In parallel to the lowering of plasma glucose, an increase of plasma beta-endorphin-like immunoreactivity was observed. In addition, naloxone and naloxonazine at doses sufficient to block opioid mu-receptors inhibited the plasma glucose-lowering action of Rh2 in genetically wild-type, diabetic mice. In contrast, Rh2 failed to lower plasma glucose in opioid mu-receptor knockout diabetic mice. An increase in gene expression at both the mRNA and protein levels of glucose transporter subtype 4 (GLUT 4) was observed in soleus muscle obtained from STZ-diabetic rats treated with Rh2 three times daily for one day; this increase in expression was absent when opioid mu-receptors were blocked. In conclusion, our results suggest that ginsenoside Rh2 may lower plasma glucose in STZ-diabetic rats based on an increase in beta-endorphin secretion that activates opioid mu-receptors thereby resulting in an increased expression of GLUT 4.
Increase of insulin secretion by ginsenoside Rh2 to lower plasma glucose in Wistar rats.:Clin Exp Pharmacol Physiol. 2006 Jan-Feb;33(1-2):27-32.Lee WK, Kao ST, Liu IM, Cheng JT.Graduate School of Chinese Traditional Medicine, China Medical University, Taichung City, Taiwan, ROC.
1. The aim of the present study was to clarify the role of ginsenoside Rh2 as the active compound in Panax ginseng root for lowering plasma glucose in animals. 2. Plasma glucose was assessed using the glucose oxidase method. Changes in the levels of insulin and C-peptide in plasma were measured by ELISA using commercially available kits. 3. After intravenous injection into fasting Wistar rats for 60 min, ginsenoside Rh2 (0.1-1.0 mg/kg) decreased plasma glucose in a dose-dependent manner. In parallel with the decrease in plasma glucose, increases in plasma insulin levels, as well as plasma C-peptide, were observed in rats receiving the same treatment. These effects of Rh2 were reversed by atropine (0.1-1.0 mg/kg), but not affected by the ganglionic nicotinic antagonists pentolinium or hexamethonium (both at 7.5 mg/kg). 4. Disruption of synaptically available acetylcholine (ACh) using an inhibitor of choline uptake (hemicholinium-3; 1-10 microg/kg) or an inhibitor of vesicular ACh transport (vesamicol; 1.5-3.5 mg/kg) abolished the actions of Rh2. In addition, physostigmine (0.1-0.5 mg/kg), at a concentration sufficient to inhibit acetylcholinesterase, enhanced the actions of the ginsenoside Rh2. Thus, mediation of the effects of Rh2 to enhance insulin secretion by ACh released from nerve terminals can be considered. 5. Blockade of the increase in plasma insulin and the plasma glucose-lowering action of Rh2 by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP; 5-10 microg/kg) indicates the participation of muscarinic M(3) receptors. Increases in plasma C-peptide level induced by Rh2 were also sensitive to 4-DAMP. 6. The results of the present study suggest that ginsenoside Rh2 has the ability to increase insulin secretion as a result of the release of ACh from nerve terminals that then stimulates muscarinic M(3) receptors in pancreatic cells. This finding shows the mechanism for the plasma glucose-lowering action of ginsenoside Rh2, that is one of the major principles contained in P. ginseng root. Thus, ginsenoside Rh2 may be applied as an adjuvant for the management of diabetes.
Identification of anxiolytic ingredients in ginseng root using the elevated plus-maze test in mice.:Eur J Pharmacol. 2006 Feb 15;531(1-3):160-5. Epub 2006 Jan 18.
Ginseng root has been widely used for the management of anxiety and emotional instability, but there is little experimental evidence supporting these clinical applications. We pharmacologically identified the anxiolytic components in ginseng root, using the elevated plus-maze test. Male ICR albino mice and the following drugs were used: diazepam (0.5, 1 and 1.5 mg/kg, p.o.); red ginseng powder (300, 600 and 1200 mg/kg, p.o.); crude saponin and non-saponin ginseng fractions (50, 100 and 200 mg/kg, i.p., for each preparation); and pure ginsenoside Rb1, Rg1, and Ro (2.5, 5 and 10 mg/kg, i.p., for each preparation). Ginseng powder and crude saponin ginseng fraction significantly increased the frequency and duration of open arm entries. Among the three types of pure ginsenoside, only ginsenoside Rb1 significantly increased both the frequency and duration of open arm entries. Our results clearly indicate that ginsenoside Rb1 is one of the active anxiolytic components of ginseng root.
Protective role of Panax ginseng extract standardized with ginsenoside Rg3 against acrylamide-induced neurotoxicity in rats.:J Appl Toxicol. 2006 May-Jun;26(3):198-206.Mannaa F, Abdel-Wahhab MA, Ahmed HH, Park MH.Medical Physiology Department, National Research Centre, Dokki, Cairo, Egypt.
Acrylamide (ACR) is an industrial neurotoxic chemical that has been recently found in carbohydrate-rich foods cooked at high temperatures. ACR was designated as a probable human carcinogen by IARC (1994) and USEPA (1988). Panax ginseng extract has efficacies such as anticancer, antihypertension, antidiabetes and antinociception. The objective of the current study is to evaluate the protective effects of Panax ginseng extract against ACR-induced toxicity in rats. Sixty adult Sprague Dawley female rats were divided into six groups included a control group, a group treated orally with ACR (50 mg kg(-1) body weight; b.w.) for 11 days, a group treated orally with Panax ginseng extract (20 mg kg(-1) b.w.) for 11 days and groups treated orally with Panax ginseng for 11 days before, during or after 11 days of ACR treatment. The results indicated that treatment with ACR alone resulted in a significant increase in lipid peroxidation level and LDH activity in brain homogenate as well as in serum CK activity, whereas it caused a significant decrease in SOD activity and a small but statistically insignificant decrease in Na(+)K(+)-ATPase activity in brain homogenate. Serum serotonin, corticosterone, T3, T4, TSH, estradiol, progesterone and plasma adrenaline were significantly decreased in ACR-treated rats. Treatment with Panax ginseng before, during or after ACR treatment reduced or partially antagonized the effects induced by ACR towards the normal values of controls. It could be concluded that Panax ginseng extract exhibited a protective action against ACR toxicity and it is worth noting that treatment with Panax ginseng extract before or at the same time as ACR treatment was more effective than when administered after ACR treatment.
Study on the extraction recovery of ginsenoside Re in plasma by different solid-phase cartridges.:Zhongguo Zhong Yao Za Zhi. 2005 Oct;30(19):1516-8. Chinese.Mao XJ, Zhang CF, Sun D, Sheng LS, Wang GJ, Liu WY.China Pharmaceutical University, Nanjing 210009, China.
OBJECTIVE: To optimize the solid-phase extraction method by comparison of the extraction recovery of ginsenoside Re plasma samples. METHOD: After extracted by different solid-phase cartridges with water, acetonitrile, and different content methanol elution, the plasma samples were analyzed on an Zorbax SB-C18 column with acetonitrile-water gradient elution. From the recovery achieved, the best solid phase cartridge was found. RESULT: This method consists of using 40% methanol as the wash solvent, and 80% methanol for the elution. Among the three kinds of solid-phase being tested, Waters Oasis HLB cartridge was found to be the best one. CONCLUSION: The average extraction recovery of the Waters Oasis HLB cartridges was between 103%-113%, it can be used in the analysis of ginsenoside Re in plasma samples.
Elucidation of the mechanisms underlying the angiogenic effects of ginsenoside Rg(1) in vivo and in vitro.:Angiogenesis. 2005;8(3):205-16. Epub 2005 Nov 22. Erratum in: Angiogenesis. 2007;10(1):69.Yue PY, Wong DY, Ha WY, Fung MC, Mak NK, Yeung HW, Leung HW, Chan K, Liu L, Fan TP, Wong RN.Hung Lai Ching Laboratory of Biomedical Science, Research and Development Division, School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong.
The major active constituents of ginseng are ginsenosides, and Rg(1) is a predominant compound of the total extract. Recent studies have demonstrated that Rg(1) can promote angiogenesis in vivo and in vitro. In this study, we used a DNA microarray technology to elucidate the mechanisms of action of Rg(1). We report that Rg(1) induces the proliferation of HUVECs, monitored using [(3)H]-thymidine incorporation and Trypan blue exclusion assays. Furthermore, Rg(1) (150-600 nM) also showed an enhanced tube forming inducing effect on the HUVEC. Rg(1) was also demonstrated to promote angiogenesis in an in vivo Matrigel plug assay, and increase endothelial sprouting in the ex vivo rat aorta ring assay. Differential gene expression profile of HUVEC following treatment with Rg(1) revealed the expression of genes related to cell adhesion, migration and cytoskeleton, including RhoA, RhoB, IQGAP1, CALM2, Vav2 and LAMA4. Our results suggest that Rg(1) can promote angiogenesis in multiple models, and this effect is partly due to the modulation of genes that are involved in the cytoskeletal dynamics, cell-cell adhesion and migration.
Pharmacokinetics of a ginseng saponin metabolite compound K in rats.:Biopharm Drug Dispos. 2006 Jan;27(1):39-45.Paek IB, Moon Y, Kim J, Ji HY, Kim SA, Sohn DH, Kim JB, Lee HS.College of Pharmacy and Medicinal Resources Research Institute, Wonkwang University, Iksan 570-749, Republic of Korea.
The absorption, dose-linearity and pharmacokinetics of compound K, a major intestinal bacterial metabolite of ginsenosides, were evaluated in vitro and in vivo. Using the Caco-2 cell monolayers, compound K showed moderate permeability with no directional effects, thus suggesting passive diffusion. After intravenous dose (i.v.; 1, 2, and 10 mg/kg), no significant dose-dependency was found in Cl (17.3-31.3 ml/min/kg), Vss (1677-2744 ml/kg), dose-normalized AUC (41.8-57.8 microg.min/ml based on 1 mg/kg) and t1/2. The extent of urinary excretion was minimal for both i.v. and oral doses. The extent of compound K recovered from the entire gastrointestinal tract at 24h were 24.4%-26.2% for i.v. doses and 54.3%-81.7% for oral doses. Following oral administration (doses 5-20 mg/kg), dose-normalized AUC (based on 5 mg/kg) was increased at the 20 mg/kg dose (85.3 microg.min/ml) compared with those at lower doses (4.50-10.5 microg.min/ml). Subsequently, the absolute oral bioavailability (F) was increased from 1.8%-4.3% at the lower doses to 35.0% at the 20 mg/kg dose. The increased F could be related to the saturation of carrier-mediated hepatic uptake and esterification of compound K with fatty acids in the liver.
Ginsenoside Rf, a component of ginseng, regulates lipoprotein metabolism through peroxisome proliferator-activated receptor alpha:Biochem Biophys Res Commun. 2006 Jan 6;339(1):196-203. Epub 2005 Nov 10.Lee H, Gonzalez FJ, Yoon M.Department of Life Sciences, Mokwon University, Taejon 302-729, Republic of Korea.
We investigated whether ginseng regulates lipoprotein metabolism by altering peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated pathways, using a PPARalpha-null mouse model. Administration of ginseng extract, ginsenosides, and ginsenoside Rf (Rf) to wild-type mice not only significantly increased basal levels of hepatic apolipoprotein (apo) A-I and C-III mRNA compared with wild-type controls, but also substantially reversed the reductions in mRNA levels of apo A-I and C-III expected following treatment with the potent PPARalpha ligand Wy14,643. In contrast, no effect was detected in the PPARalpha-null mice. Testing of eight main ginsenosides on PPARalpha reporter gene expression indicated that Rf was responsible for the effects of ginseng on lipoprotein metabolism. Furthermore, the inhibition of PPARalpha-dependent transactivation by Rf seems to occur at the level of DNA binding. These results demonstrate that ginseng component Rf regulates apo A-I and C-III mRNA and the actions of Rf on lipoprotein metabolism are mediated via interactions with PPARalpha.
The Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune response.:Vaccine. 2005 Nov 16;23(46-47):5411-9.Rivera E, Ekholm Pettersson F, Ingan?s M, Paulie S, Gr?nvik KO.National Veterinary Institute, Department of Vaccine Research, P.O. Box 7073, SE-751 89 Uppsala, Sweden. esteban.rivera@sva.se
Porcine parvovirus (PPV) vaccines containing different adjuvants were evaluated for inducing Th1 or Th2 type of immunity in mice. Isotypes of antigen specific antibodies and levels of cytokines in serum and in lymphocyte culture supernatants measured by ELISA and the Gyrolab Bioaffy were used to determine the polarisation of the immune response. Enumeration of cytokine secreting cells was carried out by ELISPOT assays. Vaccines containing the ginseng-fraction Rb1 induced serum-detectable amounts of IL-4 and IL-10 as early as 24h after primary injection that was confirmed in sera collected at 24 and 72 h post re-vaccination. Five weeks after booster, immune lymphocytes were still producing large amounts of cytokines including IFN-gamma, IL-2, IL-4, IL-10 and TNF-alpha and the antibody titres were still similar to those titres recorded 1 week post booster. The Rb1 adjuvanted vaccines stimulated similar titres of antigen specific IgG1, IgG(2a) and IgG(2b). Thus, the cytokine and the serological data indicated that the Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune response.
Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect.:Biol Pharm Bull. 2005 Oct;28(10):1903-8.Bae EA, Shin JE, Kim DH.College of Pharmacy, Kyung Hee University; 1. Hoegi, Seoul, 130-701 Korea.
To understand the relationship between the metabolism and biological activity of ginsenoside Re, a main protopanaxatriol saponin in Panax ginseng C. A. MEYER, its metabolic pathway and estrogenic effect by human intestinal microflora were investigated. All human fecal specimens metabolized ginsenoside Re, mainly to ginsenoside Rh1 and ginsenoside F1, via ginsenoside Rg1, with protopanaxadiol as a minor component. Almost all isolated ginsenoside Re-metabolizing intestinal bacteria (GHIB) also metabolized ginsenoside Re, mainly to ginsenosides Rh1 and F1, via ginsenoside Rg1. Alpha-Rhamnosidase and beta-glucosidase, partially purified from the most potent GHIB, Bacteroides JY-6, hydrolyzed ginsenoside Re and ginsenoside Rg1, respectively; however, they did not hydrolyze ginsenosides Rh1 and F1. These findings suggest that the ginsenosides Rh1 and/or F1 may not be suitable substrates of intestinal bacteria, particularly Bacteroides JY-6. The estrogenic effects of ginsenoside Re and its main metabolites, ginsenosides Rg1 and Rh1, were also investigated. Ginsenoside Rh1 showed the greatest estrogenic effect in human breast carcinoma MCF-7 cells. Based on these findings, the estrogenic effect of ginsenoside Re may be expressed by intestinal microflora.
Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb(1), that upregulates Bcl-x(L) expression.:J Cereb Blood Flow Metab. 2006 May;26(5):708-21.
Almost all agents that exhibit neuroprotection when administered into the cerebral ventricles are ineffective or much less effective in rescuing damaged neurons when infused into the blood stream. Search for an intravenously infusible drug with a potent neuroprotective action is essential for the treatment of millions of patients suffering from acute brain diseases. Here, we report that postischemic intravenous infusion of a ginseng saponin, ginsenoside Rb(1) (gRb(1)) (C(54)H(92)O(23), molecular weight 1109.46) to stroke-prone spontaneously hypertensive rats with permanent occlusion of the middle cerebral artery distal to the striate branches significantly ameliorated ischemia-induced place navigation disability and caused an approximately 50% decrease in the volume of the cortical infarct lesion in comparison with vehicle-infused ischemic controls. In subsequent studies that focused on gRb(1)-induced expression of gene products responsible for neuronal death or survival, we showed that gRb(1) stimulated the expression of the mitochondrion-associated antiapoptotic factor Bcl-x(L) in vitro and in vivo. Moreover, we revealed that a Stat5 responsive element in the bcl-x promoter became active in response to gRb(1) treatment. Ginsenoside Rb(1) appears to be a promising agent not only for the treatment of cerebral stroke, but also for the treatment of other diseases involving activation of mitochondrial cell death signaling.
Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury.:Liver Int. 2005 Oct;25(5):1069-73.Lee HU, Bae EA, Han MJ, Kim NJ, Kim DH.College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-ku, Seoul 130-701, Korea.
BACKGROUND/AIM: The main component of Panax ginseng, which have been reported by many researchers, are ginsenoside Rb1, Rb2 and Rc. Orally administered ginsenosides are metabolized to 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (compound K) by intestinal bacteria and absorbed to blood. To understand its hepatoprotective effect and its mechanism, the effects of ginsenoside Rb1 and its metabolite compound K on chemically injured HepG2 cells and mice were investigated. METHODS: Ginsenoside Rb1 and compound K were isolated from ginseng. Hepatotoxicity of HepG2 cells and mice was induced by tert-butyl hydroperoxide (t-BHP). Cytotoxicity for HepG2 cells and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) for mice as markers of hepatoprotective activity were measured. RESULTS: Compound K protected HepG2 cell cytotoxicity induced by t-BHP. However, ginsenoside Rb1 did not inhibit cytotoxicity. Nevertheless, both ginsenoside Rb1 and compound K significantly inhibited the increment of ALT and AST induced by t-BHP in mice, when it was orally administered. However, intraperitoneally administered ginsenoside Rb1 did not inhibit the increment of plasma ALT and AST induced by t-BHP in mice. These compounds did not exhibit antioxidant activity. However, compound K showed the potent membrane stabilizing activity more than ginsenoside Rb1. CONCLUSION: Compound K, which was produced from ginsenosides of Panax ginseng in intestine, could protect liver injury.
Determination of ginsenoside compound-K by reversed-phase high performance liquid chromatography.:Se Pu. 2005 May;23(3):270-2. Chinese.Zhou W, Luo Z, Zhou P.Department of Biosynthetic Drug, School of Pharmacy, Fudan University, Shanghai 200032, China.
Ginsenoside compound-K content in ginseng is very low, while it is the main intestinal bacterial metabolite and the final absorption style of the major components, such as ginsenosides Rbl and Rb2. The determination of ginsenoside compound-K in the fermentation liquor of ginseng saponins by reversed-phase high performance liquid chromatography was established. The separation was carried out under the following conditions: a Waters Symmetry C18 column (4.6 mm i.d. x 150 mm, 5 microm) was used at 35 degrees C with acetonitrile-water (48:52, v/v) as mobile phase at a flow rate of 1 mL/min. UV detection wavelength was set at 203 nm. The experimental results showed a good linear relationship between the peak area and mass concentration for ginsenoside compound-K within the range of 0.05-0.8 g/L (r = 0.9998). The relative standard deviation of peak area (n = 6) was 2.20%. The lowest detection limit (S/N = 3) was 2.5 mg/L. The average recoveries (n = 3) for the culture broth of ginseng saponins and notoginseng saponins were 98.6% and 99.7%, respectively. The method is rapid, simple, accurate and reproducible and can be utilized for the research and development of ginsenoside compound-K in pharmaceutical industry.
Pharmacokinetics of ginsenosides Rg1 and Re in Shenmai injection.:Yao Xue Xue Bao. 2005 Apr;40(4):365-8. Chinese.Liu YM, Yang L, Zeng X, Deng YH, Feng Y, Liang WX.Department of Clinical Pharmacology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, China.
AIM: To study the pharmacokinetics of ginsenosides Rg1 and Re after iv infusion of Shenmai injection in human. METHODS: Ginsenosides Rg1 and Re in plasma were determined by LC/MS/MS and the pharmacokinetic parameters were calculated. RESULTS: The linear regressive curves were obtained in the range of 1.023-1023 microg x L(-1) for Rg1 and 1.05-1050 microg x L(-1) for Re. Recoveries using the method of Rg1 and Re were 99%-105% and 99%-104%, respectively. The within-day and between-day RSDs were less than 15%. After iv infusion of Shenmai injection to volunteers, the concentration-time curves of Rg1 and Re fitted to the two-compartment model, T1/2alpha were 0.28 h and 0.10 h, T1/2beta were 2.1 h and 1.2 h, respectively. CONCLUSION: The method is specific, simple, sensitive and suitable for the measurement of plasma Rg1 and Re concentrations. The distribution and elimination of Rg1 and Re were rapid after iv infusion of Shenmai injection in volunteers, the pharmacokinetic characteristics were fitted with the two-compartment model.
Radioprotective potential of ginseng.:Mutagenesis. 2005 Jul;20(4):237-43. Epub 2005 Jun 14. Review.Lee TK, Johnke RM, Allison RR, O'Brien KF, Dobbs LJ Jr.Department of Radiation Oncology, Leo W.Jenkins Cancer Center, Brody School of Medicine at East Carolina University, Greenville, NC 27858, USA. leet@mail.ecu.edu
A majority of potential radioprotective synthetic compounds have demonstrated limited clinical application owing to their inherent toxicity, and thus, the seeking of naturally occurring herbal products, such as ginseng, for their radioprotective capability has become an attractive alternative. In general, ginseng refers to the roots of the species of the genus Panax. As a medicinal herb, ginseng has been widely used in traditional Chinese medicine for its wide spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic, adaptogenic and antiaging activities. Many of its medicinal effects are attributed to the triterpene glycosides known as ginsenosides (saponins). This review addresses the issue of the radioprotective effects of ginseng on mammalian cells both in vitro and in vivo. Results indicate that the water-soluble extract of whole ginseng appears to give a better protection against radiation-induced DNA damage than does the isolated ginsenoside fractions. Since free radicals play an important role in radiation-induced damage, the underlying radioprotective mechanism of ginseng could be linked, either directly or indirectly, to its antioxidative capability by the scavenging free radicals responsible for DNA damage. In addition, ginseng's radioprotective potential may also be related to its immunomodulating capabilities. Ginseng is a natural product with worldwide distribution, and in addition to its antitumor properties, ginseng appears to be a promising radioprotector for therapeutic or preventive protocols capable of attenuating the deleterious effects of radiation on human normal tissue, especially for cancer patients undergoing radiotherapy.
Evaluation of measurement uncertainty for the determination of ginsenosides in Radix ginseng by HPLC.:Yao Xue Xue Bao. 2005 Jan;40(1):49-53. Chinese.Hu P, Luo GA, Zhao ZZ, Chan KK, Jiang ZH.School of Chemistry and Pharmaceutics, East China University of Science and Technology, Shanghai 200237, China.
AIM: To set out the procedure for estimation of measurement uncertainty for the determination of ginsenosides R(g1), Re and R(b1) in Radix ginseng by HPLC. METHODS: To facilitate the identification and analysis of the uncertainty sources arising from the procedure of analysis, a cause and effect diagram was constructed and simplified. Each uncertainty component whether associated with individual sources or with the combined effects of several sources, was evaluated with respect to the significance of its contribution to the overall measurement uncertainty and was expressed as standard uncertainty. All the standard uncertainties were then combined according to the appropriate rules to give a combined standard uncertainty and an expanded standard uncertainty. Results The expanded standard uncertainties for the HPLC determination of ginsenoside R(g1), Re, and R(b1), are 0.12c, 0.14c and 0.13c, respectively. CONCLUSION: Measurement uncertainty is applicable to set the limit of the ginsenosides in Radix ginseng. The establishment of the methodology for the evaluation of measurement uncertainty is important to the studies of Chinese materia medica standards.
A natural compound (ginsenoside Re) isolated from Panax ginseng as a novel angiogenic agent for tissue regeneration.:Pharm Res. 2005 Apr;22(4):636-46. Epub 2005 Apr 7. Huang YC, Chen CT, Chen SC, Lai PH, Liang HC, Chang Y, Yu LC, Sung HW.Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
PURPOSE: The primary challenge for tissue engineering is to develop a vascular supply that can support the metabolic needs of the engineered tissues in an extracellular matrix. In this study, the feasibility of using a natural compound, ginsenoside Re, isolated from Panax ginseng in stimulating angiogenesis and for tissue regeneration was evaluated. METHODS: Effects of ginsenoside Re on the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) were examined in vitro. Additionally, angiogenesis and tissue regeneration in a genipin-fixed porous acellular bovine pericardium (extracellular matrix; ECM) incorporated with ginsenoside Re implanted subcutaneously in a rat model were investigated. Basic fibroblast growth factor (bFGF) was used as a control. RESULTS: It was found that HUVEC proliferation, migration in a Transwell plate, and tube formation on Matrigel were all significantly enhanced in the presence of bFGF or ginsenoside Re. Additionally, effects of ginsenoside Re on HUVEC proliferation, migration, and tube formation were dose-dependent and reached a maximal level at a concentration of about 30 microg/ml. The in vivo results obtained at 1 week postoperatively showed that the density of neocapillaries and the tissue hemoglobin content in the ECMs were significantly enhanced by bFGF or ginsenoside Re. These results indicated that angiogenesis in the ECMs was significantly enhanced by loading with bFGF or ginsenoside Re. At 1 month postoperatively, vascularzied neo-connective-tissue fibrils were found to fill the pores in the ECMs loaded with bFGF or ginsenoside Re. CONCLUSIONS: The aforementioned results indicated that like bFGF, ginsenoside Re-associated induction of angiogenesis enhanced tissue regeneration, supporting the concept of therapeutic angiogenesis in tissue-engineering strategies.
Isoginsenoside-Rh3, a new triterpenoid saponin from the fruits of Panax ginseng C. A. Mey.:J Asian Nat Prod Res. 2004 Dec;6(4):289-93.Wang JY, Li XG, Zheng YN, Yang XW.College of Chinese Medicine Material, Jilin Agricultural University, Changchun, China.
A new dammarane-type triterpene monoglucoside, named isoginsenoside-Rh(3), has been isolated from the fruits of Panax ginseng C. A. Mey, together with eight known analogs, ginsenoside-Rb(1), -Rb(2), -Rc, -Rd, -Re, -Rg(1), -Rh(1), -Rh(2). On the basis of chemical and physicochemical evidence, the structure of isoginsenoside-Rh(3) has been elucidated as 3-O-beta--glucopyranosyl-dammarane-(E)-20(22),24-diene-3beta,12beta-diol (1).
Comparative study on triterpene saponins of Ginseng drugs.:Planta Med. 2004 Jul;70(7):666-77
A comparative study on the triterpene saponins of 47 samples of Ginseng drugs derived from 12 Panax taxa was conducted using a reverse-phase high-performance liquid chromatography (HPLC)method. Eleven ginsenosides, which represent 4 types of typical sapogenins, were chosen as standards for quantitative determination in order to characterize the chemical constituent pattern of each Ginseng drug and investigate the relationship between genetic varieties and chemical constituent pattern. The results showed that the ginsenoside compositions in Ginseng drugs of different origins were of considerable variability. Total saponin contents varied by 10-fold from the highest drug to the lowest one. Chikusetsu-ninjin derived from P. japonicus (Japan) was found to have the highest content (192.80 - 296.18 mg/g) and Ginseng from P. ginseng to be the lowest (5.78 - 15.63 mg/g).Two main groups (I and II) suggested by phytochemical data were clearly observed; group I mainly containing dammarane saponins consisted of P. ginseng, P. quinquefolius, P. notoginseng, P. vietnamensis and P. vietnamensis var. fuscidiscus; and group II containing a large amount of oleanolic acid saponins was com-posed of P.japonicus (apan), P. zingiberensis, P.japonicus (China),P. japonicus var. angustifolius, P. japonicus var. major, P. japonicus var. bipinnatifidus and P. stipuleanatus. The ratios of the subtotal of dammarane saponins to that of oleanolic acid saponins (D/0) were found to be > 1.9 and < 0.25 for groups I and II, respectively.The drug samples derived from the same botanical origin revealed similar constituent patterns, in other words, each Panaxtaxon showed its own characteristic chromatographic profile,which appeared in the specific shape of an 11-direction radar graph constructed on the basis of the result of quantitative analysis. Similarities of chemical constitution were seen among the closely phylogenetically-related taxa, including P. ginseng and P.quinquefolius, P. vietnamensis and P. vietnamensis var.fuscidiscus,P. japonicus (China) and its varieties were demonstrated, except P. japonicus (Japan) and P. zingiberensis.
The relationship between the protection of ginsenoside for spinal cell and nitric oxide.:Zhongguo Zhong Yao Za Zhi. 2003 Sep;28(9):851-3. Chinese.Pan SY, Pan XW, Wang SP.Center of Army Hyperbaric Oxygen, General Navy Hospital, Beijing 100037, China.
OBJECTIVE: To study the relationship between the protection of Ginsenoside(GS) for spinal cells and nitric oxide (NO). METHOD: Spinal cells were cultured in vitro, the model of peripheral nerve was established by scarifying the cells, and NO was measured by Griess method. RESULT: NO in injury group was high than that in noninjury group and NO in group cultured by GS was less than that in group cultured by common medium. CONCLUSION: NO increases when peripheral nerve is injuried, and the protective effect of GS on spinal cells may be through inhibiting NO release.
Study on the chemical constituents of the roots of commercial ginseng.:Zhongguo Zhong Yao Za Zhi. 2003 Jun;28(6):522-4. Chinese.Dou DQ, Ren J, Chen Y, Pei YP, Chen YJ.Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China. doudeqiang@hotmail.com
OBJECTIVE: To isolate and elucidate the constituents from the roots of Commercial Ginseng. METHOD: Column chromatography and HPLC were used to isolate chemical constituents. Physico-chemical characters and spectr-oscopic analysis were employed for structural identification. RESULT: Sixteen compounds were identified as: notoginsenoside-R2(1), ginsenoside-Rg2(2), 20 (R)-Rg2 (3), ginsenoside-Rg1 (4), -Rf(5), -Re(6), -Rd(7), -Rc(8), -Rb1(9), -Rb2(10), -Rb3(11), -Ra3(12), -Ra2(13), -Ra1 (14), notoginsenoside-R4(15) and ginsenoside -Ro(16). CONCLUSION: Compound 1 was obtained from the plant for the first time.
Ginsenoside Rh2 reduces ischemic brain injury in rats.:Biol Pharm Bull. 2004 Mar;27(3):433-6.Park EK, Choo MK, Oh JK, Ryu JH, Kim DH.College of Pharmacy, Kyung Hee University, Hoegi, Dongdaemun-ku, Seoul, Korea.
Ginseng was incubated under mildly acidic conditions and its inhibitory effect on a rat ischemia-reperfusion model was investigated. When ginseng was treated with 0.1% hydrochloric acid at 60 degrees C, its protopanaxadiol saponins were transformed to diasteromeric ginsenoside Rg3 and Delta20-ginsenoside Rg3. When the transformed ginseng extract, of which the main component was ginsenosides Rg3, was treated with human intestinal microflora, the main metabolite was ginsenoside Rh2. Orally administered acid-treated ginseng (AG) extract and ginsenoside Rh2 potently protect ischemia-reperfusion brain injury. The ginsenoside Rh2 also inhibited prostaglandin-E2 synthesis in lipopolysaccharide-stimulated RAW264.7 cells, but showed no in vitro antioxidant activity. These results suggest that AG and ginsenoside Rh2 can improve ischemic brain injury.
Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities.:Int Arch Allergy Immunol. 2004 Feb;133(2):113-20. Epub 2004 Jan 21.Park EK, Choo MK, Han MJ, Kim DH.College of Pharmacy, Kyung Hee University, Seoul, Korea.
BACKGROUND: Ginseng (the root of Panax ginseng C.A. Meyer, Araliaceae) has been reported to possess various biological activities, including anti-inflammatory and antitumor actions. In this study, we investigated the antiallergic activity of ginsenosides isolated from ginseng. METHOD: We isolated ginsenosides by silica gel column chromatography and examined their in vitro and in vivo antiallergic effect on rat peritoneal mast cells and on IgE-induced passive cutaneous anaphylaxis (PCA) in mice. The in vitro anti-inflammatory activity of ginsenoside Rh1 (Rh1) in RAW264.7 cells was investigated. RESULTS: Rh1 potently inhibited histamine release from rat peritoneal mast cells and the IgE-mediated PCA reaction in mice. The inhibitory activity of Rh1 (87% inhibition at 25 mg/kg) on the PCA reaction was found to be more potent than that of disodium cromoglycate (31% inhibition at 25 mg/kg); Rh1 was also found to have a membrane-stabilizing action as revealed by differential scanning calorimetry. It also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in RAW 264.7 cells, and the activation of the transcription factor, NF-kappaB, in nuclear fractions. CONCLUSION: The antiallergic action of Rh1 may originate from its cell membrane-stabilizing and anti-inflammatory activities, and can improve the inflammation caused by allergies.
Ginsenoside Rb1: the anti-ulcer constituent from the head of Panax ginseng.:Arch Pharm Res. 2003 Nov;26(11):906-11.Jeong CS, Hyun JE, Kim YS.College of Pharmacy, Duksung Womens University, 419 Ssangmun-dong, Dobong-ku, Seoul 132-714, Korea. choonsik@duksung.ac.kr
We previously reported that the butanol (BuOH) fraction of the head of Panax ginseng exhibited gastroprotective activity in peptic and chronic ulcer models. In order to identify the active constituent, an activity-guided isolation of the BuOH faction was conducted with a HCl x ethanol-induced gastric lesion model. The BuOH fraction was passed through a silica-gel column using a chloroform-methanol gradient solvent system, and six fractions (frs. 1-6) were obtained. The active fr. 5 was further separated by silica-gel column, to yield 6 subfractions (subfrs. a-f). Subfr. d was composed of ginsenosides Re, Rc and Rb1. The most active constituent was ginsenoside Rb1 (GRb1), a protopanaxadiol glycoside, which was investigated for its anti-ulcer effect. Gastric injury induced by HCl x ethanol, indomethacin and pyloric ligation (Shay ulcer) was apparently reduced with oral GRb1 doses of 150 and 300 mg/kg. GRb1 at these dosage significantly increased the amount of mucus secretion in an ethanol-induced model. The anti-ulcer effects were consistent with the result of histological examination. These results suggest that the major active constituent in the head of Panax ginseng is GRb1, and that anti-ulcer effect is produced through an increase in mucus secretion.
Antiallergic activity of ginsenoside Rh2.:Biol Pharm Bull. 2003 Nov;26(11):1581-4.Park EK, Choo MK, Kim EJ, Han MJ, Kim DH.College of Pharmacy, Kyung Hee University, Hoegi, Seoul 130-701, Korea.
The antiallergic activities of ginsenosides, which were isolated from acid-treated ginseng (Panax ginseng, Araliaceae), and their metabolites by human intestinal bacteria were measured. Ginsenoside Rh2, which is a main metabolite, had the most potent inhibitory activity on beta-hexosaminidase release from RBL-2H3 cells and in the passive cutaneous anaphylaxis reaction. The inhibitory activity of ginsenoside Rh2 was more potent than that of disodium cromoglycate, a commercial antiallergic drug. This compound showed membrane stabilizing action upon differential scanning calorimetry and inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide-stimulated RAW cells. However, this ginsenoside Rh2 did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that ginsenoside Rh2 can exhibit antiallergic activity originating from cell membrane-stabilizing activity and antiinflammatory activity by the inhibition of NO and PGE2 production.
Determination of polyacetylenes and ginsenosides in Panax species using high performance liquid chromatography.:Chem Pharm Bull. 2003 Nov;51(11):1314-7.
A new HPLC method was developed to separate and identify three polyacetylenes (panaxynol, panaxydol and 1,8-heptadecadiene-4,6-diyne-3,10-diol) found in Panax species. The mobile phase was a linear gradient of 2 : 1 : 3 to 2 : 1 : 1 (v/v/v) methanol/acetonitrile/water in 40 min. HPLC analysis was performed at a flow rate of 1.5 ml/min with UV detection at 254 nm. The contents of the polyacetylenes and ginsenosides in Panax ginseng (white ginseng and red ginseng), P. quinquefolium, P. japonicus, and P. noteginseng were determined using these methods. The species containing the highest polyacetylene content (0.080%) was P. quinquefolium cultivated in Nagano. Meanwhile, the species with the highest ginsenoside content (9.176%) was P. noteginseng cultivated in Yunnan, China.
Claims: Information this web site presented is meant for Nutritional Benefit and as an educational starting point only, for use in maintenance and promotion good health in cooperation with a common knowledge base reference...Furthermore,it based solely on the traditional and historic use or legend of a given herb from the garden of Adonis. Although every effort has been made to ensure its accurate, please note that some info may be outdated by more recent scientific developments......
Pharmakon Warning: The order of knowledge is not the transparent order of forms and ideas,as one might be tempted retrospectively to interpret it; it is the antidote....(Dissemination,Plato's Pharmacy,II.The Ingredients:Phantasms,Festivals,and Paints;138cf. Jacques Derrida.).
And as it happens,the technique of imitation,along with the production of the simulacrum,has always been in Plato's eyes manifestly magical,thaumaturgical:......and the same things appear bent and straight to those who view them in water and out,or concave and convex,owing to similar errors of vision about colors, and there is obviously every confusion of this sort in our souls.And so scene painting (skiagraphia) in its exploitation of this weakness of four nature falls nothing short of witchcraft (thaumatopoia), and so do jugglery and many other such contrivances.(Republic X,602c-d;cf.also 607c).
seminal trace...Panax ginseng extract,Radix Ginseng Extract.10:1.Panax ginseng Extract,Asian Ginseng Extract.Ginsenosides.20%~80%HPLC.Ginsenosides,M.F.:C48H82O19;MW:963.15.Fructus Panax Ginseng,Folium Panax Ginseng,Radix Panax Ginseng...
Phytochemical info of Panax ginseng.
Neuroprotective effect of individual ginsenosides on astrocytes primary culture.:Biochim Biophys Acta. 2007 Jun 28;L¨®pez MV, Cuadrado MP, Ruiz-Poveda OM, Del Fresno AM, Accame ME.Department of Pharmacology, School of Pharmacy, Complutense University, Madrid, Spain.
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