Research Update of Cordyceps sinensis and Its findings......

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   Research Update: Cordyceps sinensis and Its findings:

  Quality control of Cordyceps sinensis, a valued traditional Chinese medicine.:

 Cordyceps sinensis, a well-known and valued traditional Chinese medicine, is also called DongChongXiaCao (winter worm summer grass) in Chinese. It is commonly used to replenish the kidney and soothe the lung for the treatment of fatigue, night sweating, hyposexualities, hyperglycemia, hyperlipidemia, asthemia after severe illness, respiratory disease, renal dysfunction and renal failure, arrhythmias and other heart disease, and liver disease. As the rarity and upstanding curative effects of natural Cordyceps, several mycelial strains have been isolated from natural Cordyceps and manufactured in large quantities by fermentation technology, and they are commonly sold as health food products in Asia. In addition, some substitutes such as Cordyceps militaris also have been used and adulterants also confused the market. Therefore, quality control of C. sinensis and its products is very important to ensure their safety and efficacy. Herein, markers and analytical methods for quality control of Cordyceps were reviewed and discussed.

  Identification and determination of nucleosides in Cordyceps sinensis and its substitutes by high performance liquid chromatography with mass spectrometric detection.:

 Cordyceps sinensis (Cs) is a well-known traditional Chinese medicine (TCM) and Cordyceps mycelia (Cm), a cultured Cordyceps, is a substitute for Cordyceps sinensis. The most important active components in them are nucleosides. A high selective, sensitive and accurate high performance liquid chromatography method with photodiode array detection (DAD) and mass spectrometric detection has been developed for simultaneous separation, identification and quantification of nucleosides in Cs and Cm using a mobile phase including (A) ammonium acetate (40 mM, pH 5.2) and (B) methanol with a gradient system on a 2.0 mm x 150 mm Shimadzu VP-ODS column. The presence of each nucleoside in Cs and Cm was ascertained by comparison of MS data, UV spectra and retention time with standards. LC/ESI-MS in selective ion monitoring (SIM) mode were used for the quantification of nucleosides in Cs and Cm. 2-Chloroadenosine was used as internal standard for this assay. The precisions and accuracies were in the range of 1.5-5.3% and -3.5 to 5.0%, respectively. The limits of detection and quantification for nucleosides were in the order of 0.1-0.6 microg ml(-1) and 0.5-2.0 microg ml(-1), respectively. The recoveries were in the range of 92.0-107.0%. With the developed method, the concentrations of nucleosides in Cs and Cm from different sources were determined. Cs, characterized with far lower concentration of adenosine and cordycepin than Cm, can be very easy to distinguish from Cm. This reliable method would be useful for the study and quality control of Cordyceps sinensis and its substitutes.

  Structural analysis of a neutral (1-->3),(1-->4)-beta-D-glucan from the mycelia of Cordyceps sinensis.:

 The extracellular polysaccharide (1) extracted from the mycelia of Cordyceps sinensis with hot water was fractionated and purified by ion-exchange and gel-filtration chromatography. The structure was investigated using methylation and hydrolysis analysis, periodate oxidation, NMR spectroscopy, and reaction with beta-D-glucanase, and the results indicated that this D-glucan consisted of a backbone composed of (1-->3)-beta-D-glucosyl residues and carried a single (1-->4)-beta-linked D-glucosyl residue. NMR and IR spectroscopic measurements showed that the sugar residues were beta-glycosidically linked.

  Identification of Chinese medicinal fungus Cordyceps sinensis by PCR-single-stranded conformation polymorphism and phylogenetic relationship.:

 Fungi belonging to the Cordyceps species have long been used as food and herbal medicines in Asia and are especially popular as commercially available powdered supplements. Despite this acceptance and use, little is known of the phylogenetic relationships of the genus. Presently, the neighbor-joining method based on the ITS1, 5.8S rRNA, and ITS2 regions was used to construct a phylogenetic tree of 17 Cordyceps isolates. Five major groups were evident. Cordyceps sinensis was less closely related to 15 Cordyceps species but shared a closer relationship with Cordyceps agriota. PCR-single-stranded conformational polymorphism was applied to differentiate seven Cordyceps isolates: five were different from those used to construct the phylogenetic tree, based on differences in the internal spacer 2 (ITS2). The length of ITS2, amplified by primers 5.8SR and ITS4, vary between 334 and 400 bp. This segment could be used for intraspecies classification or detection of mutations and represents potential novel means of identification of this fungal genus in herbal medicines and in quality control applications in the fermentation industry.

  Cordycedipeptide A, a new cyclodipeptide from the culture liquid of Cordyceps sinensis (Berk.) Sacc.:

 A new cyclodipeptide named as cordycedipeptide A, a new natural compound and two known compound were isolated from the culture liquid of Cordyceps sinensis (BERK.) SACC. Their structures were elucidated as 3-acetamino-6-isobutyl-2,5-dioxopiperazine (1), 3-isopropyl-6-isobutyl-2,5-dioxopiperazine (2) and 3,6-di(4-hydroxy)benzyl-2,5-dioxopiperazine (3) by 1D and 2D-NMR techniques. The cytotoxic assay showed compound 1 had the cytotoxic activities to L-929, A375, and Hela.

  Structure analysis and antitumor activity of (1-->3)-beta-d-glucans (cordyglucans) from the mycelia of Cordyceps sinensis.:

 The cell wall polysaccharides from Cordyceps sinensis were obtained from the fresh samples of the mycelia, the material was released by successive extractions with hot water and 0.05 M sodium hydroxide solutions. The extracts were fractionated by ion-exchange and gel-filtration chromatography, respectively. Analysis of the first fraction showed that cordyglucans were the unique component. Cordyglucans were found to exhibit potent antitumor activity, this activity could be correlated to their (1-->3)-beta-d-glucan linkages.


  Simultaneous determination of ergosterol, nucleosides and their bases from natural and cultured Cordyceps by pressurized solvent extraction and high performance liquid chromatography.:

 AIM: To establish a simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps by HPLC coupled with pressurized solvent extraction (PSE). METHODS: The extraction was performed by using PSE and the PSE condition was optimized by using orthogonal test, the contents of ergosterol, nucleosides and their bases in Cordyceps were determined by HPLC. RESULTS: The optimized condition of PSE extraction for ergosterol, nucleosides and their bases in Cordyceps was obtained as follow: solvent, methanol; temperature, 160 degrees C; static extraction time, 5 min; pressure, 10 MPa and one extraction cycle and one time. A ZORBAX NH2 column (250 mm x 4.6 mm ID, 5 microm) and a ZORBAX NH2 guard column (12.5 mm x 4.6 mm ID, 5 microm) were used for simultaneous determination of ergosterol, nucleosides and their bases. Solvents that constituted the mobile phase were A (acetonitrile) and B (10 mmol x L(-1) ammonium acetate in water). The elution conditions applied were: 0 -5.0 min, linear gradient 0 --> 15% B; 5.0-25.0 min, linear gradient 15% --> 20% B; 25.0 - 35.0 min, linear gradient 20% --> 40% B; 35.0 - 45.0 min, linear gradient 40% --> 80% B; 45.0 -50.0 min, 80% B isocratic. The flow-rate was 0. 6 mL x min(-1) and the injection volume was 20 microL. The system operated at 25 degrees C. Ergosterol was monitored and quantified at 275 nm, nucleosides and their bases at 254 nm. CONCLUSION: High performance liquid chromatography coupled with pressurized solvent extraction is a rapid and simple method for simultaneous determination of ergosterol, nucleosides and their bases in Cordyceps.
 

  The effect of ultrasonication on immuno-modulating activity of mycelial polysaccharide from Cordyceps gunnii.:

 OBJECTIVE: To investigate immuno-modulating activity change after mycelial polysaccharide from Cordyceps gunnii (MPCG) was depolymerized by ultrasonication. METHODS: The effects of MPCG and its depolymerizing mixture on mice spleen lymphocytes proliferation, mice peritoneal macrophage (PMphi) phagocytosis and cytotoxin T lymphocytes (CTL) activity were studied by MTT method, neutral red colorimetry, respectively. RESULTS: In vitro, MPCG depolymerized by ultrasonication could more significantly inhibite spleen lymphocytes proliferation, PMphi phagocytosis of neutral red and CTL activity in mice than MPCG, in particular at doses of 10 microg/ml and 100 microg/ml. Whereas, four kinds of depolymerized mixture depolymerized for 1h to 2h and 4h to 8h by ultrasonication, respectively, had not evident differences at three various doses. CONCLUSION: MPCG was suitable for depolymerizing for 1h to 2h and its depolymerized mixture had stronger immuno-modulating activity than MPCG.

  Quantitative analysis of the nucleosides in Cordyceps sinensis with capillary zone electrophoresis.:

 OBJECTIVE: To establish a quantitative analysis method for analyzing the nucleosides in Cordyceps sinensis with capillary electrophoresis, and compare the difference between natural and the cultured C. mycelia. METHOD: Capillary zone electrophoresis method was employed to quantitate the adenosine, uridine, guanosine and inosine in C. sinensis, with 0.25 mg x L(-1) boric acid-sodium hydroxide buffer, pH 9.5. The working voltage was 20 kV, the temperature was 25 degrees C, and the detection wavelength was 260 nm. RESULT: With the capillary zone electrophoresis method, the average recovery of the above 4 nucleosides was 98.9%, 95.1%, 97.8% and 98.8% respectively, with the RSD 0.4%, 1.7%, 1.3% and 5.0%. There was no adenosine in natural C. sinensis and no inosine in the cultured C. mycelia detected. CONCLUSION: This method can be used to determine the adenosine, uridine, guanosine and inosine in C. sinensis. The nucleosides in C. sinensis produced from Qinghai province and cultured C. mycelia are obviously different.

  Determination of ergosterol in Cordyceps sinensis and Cordyceps black-bone chicken capsules by HPLC.:

 A high performance liquid chromatographic method (HPLC) was developed for the determination of ergosterol in Cordyceps sinensis and Cordyceps black-bone chicken capsules. The sample was mixed with 0.5 ml of saturated KOH solution and 5 ml of ethanol, and refluxed for 1 h. The saponified mixture was diluted with 5 ml of 10% NACl solution and extracted 3 times with 5 ml portions of cyclohexane. The cyclohexane extracts were purified by partition column and concentrated by adsorption column and then analysed by HPLC. The other components of the Cordyceps black-bone chicken capsules have no interference to the determination of ergosterol. The proposed method is rapid, precise, accurate and sensitive. The whole process can be done in 2 h.


  A new approach to the fast measurement of content of amino acids in Cordyceps sinensis by ANN-NIR.:

 A new method for fast determining the content of amino acid in Cordyceps sinensis by means of near infrared (NIR) spectroscopy was developed. Colorimetry was first employed to measure the actual content of amino acid in Cordyceps sinensis. BP neural network was introduced to model the quantitative correlations between the NIR spectra and the contents of glycine, arginine and total amino acid. By comparing several preprocessing procedures and wavelength ranges, the optimal models could be obtained in the range of 7501.7-6097.8 cm(-1) and 5453.7-4246.5 cm(-1) with first derivative NIR spectra. Standard errors of prediction set (RMSEP) for glycine, arginine and total amino acid were 0.08, 0.07 and 0.36, respectively. The ultimate experimental results indicated that the proposed artificial neural network model was far superior to those of partial least square regression (PLS) and principal component regression (PCR). As an effective nonlinear multivariate calibration strategy, this paper could offer a new approach to the fast measurement of content of chemical components in traditional Chinese medicine by NIR spectroscopy.

  Medium optimization for polysaccharide production of Cordyceps sinensis.:

 As a potential anticarcinogenic agent, polysaccharides from Cordyceps sinensis have been demonstrated to possess strong antioxidation activity. The aim of the present research was to study the optimal medium to produce polysaccharides of C. sinensis by using response surface methodology (RSM). The composition of optimized medium for polysaccharide production calculated from the regression model of RSM was 6.17% sucrose, 0.53% corn steep powder, 0.5% (NH4)2HPO4, and 0.15% KH2PO4 at pH 4.44, with a predicted maximum polysaccharide production of 3.17 g/L. When applying this optimal medium, the maximum polysaccharide production was 3.05 and 3.21 g/L in a shake flask and a 5-L jar fermentor, respectively. When the pH was controlled at a higher level such as pH 5.0, both cell growth and polysaccharide production were inhibited. A low pH of 2.85 was required for maximum production of polysaccharides.

  Purification and characterization of an acid deoxyribonuclease from the cultured mycelia of Cordyceps sinensis.:

 A new acid deoxyribonuclease (DNase) was purified from the cultured mycelia of Cordyceps sinensis, and designated CSDNase. CSDNase was purified by (NH(4))(2)SO(4) precipitation, Sephacryl S-100 HR gel filtration, weak anion-exchange HPLC, and gel filtration HPLC. The protein was single-chained, with an apparent molecular mass of ca. 34 kDa, as revealed by SDS-PAGE, and an isoelectric point of 7.05, as estimated by isoelectric focusing. CSDNase acted on both double-stranded (ds) and single- stranded (ss) DNA, but preferentially on dsDNA. The optimum pH of CSDNase was pH 5.5 and its optimum temperature 55. The activity of CSDNase was not dependent on divalent cations, but its enzymic activity was inhibited by high concentration of the cation: MgCl(2) above 150 mM, MnCl(2) above 200 mM, ZnCl(2) above 150 mM, CaCl(2) above 200 mM, NaCl above 300 mM, and KCl above 300 mM. CSDNase was found to hydrolyze DNA, and to generate 3-phosphate and 5-OH termini. These results indicate that the nucleolytic properties of CSDNase are essentially the same as those of other well-characterized acid DNases, and that CSDNase is a member of the acid DNase family. To our knowledge, this is the first report of an acid DNase in a fungus.

  Optimization of submerged culture process for the production of mycelial biomass and exo-polysaccharides by Cordyceps militaris C738.:

 AIMS: The objective of the present study was to determine the optimal culture conditions for mycelial biomass and exo-polysaccharide (EPS) by Cordyceps militaris C738 in submerged culture. METHODS AND RESULTS: The optimal temperatures for mycelial biomass and EPS production were 20 degrees C and 25 degrees C, respectively, and corresponding optimal initial pHs were found to be 9 and 6, respectively. The suggested medium composition for EPS production was as follows: 6% (w/v) sucrose, 1% (w/v) polypeptone, and 0.05% (w/v) K2HPO4. The influence of pH on the fermentation broth rheology, morphology and EPS production of C. militaris C738 was carried out in a 5-l stirred-tank fermenter. The morphological properties were comparatively characterized by pellet roughness and compactness by use of image analyser between the culture conditions with and without pH control. The roughness and compactness of the pellets indicated higher values at pH-stat culture (pH 6.0), suggesting that larger and more compact pellets were desirable for polysaccharide production (0.91 g g(-1) cell d(-1). CONCLUSIONS: Under the optimized culture conditions (with pH control at 6), the maximum concentration of biomass and EPS were 12.7 g l(-1) and 7.3 g l(-1), respectively, in a 5-l stirred-tank fermenter. SIGNIFICANCE AND IMPACT OF THE STUDY: The critical effect of pH on fungal morphology and rheology presented in this study can be widely applied to other mushroom fermentation processes.
 


  The fruiting body and its caterpillar host of Cordyceps sinensis show close resemblance in main constituents and anti-oxidation activity.:

 Cordyceps (summer-grass, winter-worm), one of the most valued traditional Chinese medicines, is used commonly for the replenishment of body health. It consists of the dried fungus Cordyceps sinensis growing on caterpillar larvae. For medication, the fruiting body (fungus) and the worm (caterpillar) are used together. However, the pharmacological efficiency and the main constituents of the individual parts have not been determined. In the present study the water extracts from the fruiting body and worm of natural Cordyceps were analyzed for their content of nucleosides and polysaccharides; the results showed that the worm had chemical composition similar to the fruiting body. In addition, both the fruiting body and worm of Cordyceps showed similar potency in their anti-oxidation activities in the xanthine oxidase assay, the induction of hemolysis assay and the lipid-peroxidation assay. These results suggest that the function of the worm in Cordyceps is to provide a growth medium for the fruiting body, and that eventually, the worm is totally invaded by C. sinensis mycelia.

  RP-HPLC determination of adenosine in fermented Cordyceps.:

 OBJECTIVE: A method for determination of adenosine in four fermented Cordyceps products by RP-HPLC is described. METHOD: C18 column was used with methanol-0.06 mol/L potassium phosphate monobasic-tetrahydrofuran (10:150:1.5) as mobile phase. The flow rate was 1 ml/min and detected at 260 nm. RESULTS: The average recovery was 98.7% and relative standard deviation was 1.10% (n = 5). CONCLUSION: This method is simple, rapid and sensitive. The paper introduces the feasibility of supersonic extraction method taking the place of reflux method.

  Free radical scavenging and apoptotic effects of Cordyceps sinensis fractionated by supercritical carbon dioxide.:

 Supercritical carbon dioxide (SC-CO2) was used as the elution solvent for fractioning ethanolic extract (E) of Cordyceps sinensis (CS), a traditional Chinese herbal remedy, into R, F1, F2, and F3 fractions. This extractive fractionation method is amenable to large scale and is nontoxic. These four fractions were characterized in terms of total polysaccharides and cordycepin concentrations, scavenging ability of free radicals, and anti-tumor activities. Experimental results demonstrated that fractionation altered the distributions of total polysaccharides and cordycepin in fractions. Fraction R was the most active fraction to scavenge free radicals and inhibit the proliferation of carcinoma cells, followed by the fraction F1 and the extract E. The effect of scavenging on 1,1-diphenyl-2-picryl hydrazyl (DPPH) of CS extract and fractions at 2 mg/ml was R (93%), F1 (75%), E (66%), F2 (47%), and F3 (27%). The IC50 (50% cell growth inhibitory concentration) of tumor cell proliferation and colony formation on human colorectal (HT-29 and HCT 116) and hepatocellular (Hep 3B and Hep G2) carcinoma cells by fraction R were around 2 microg/ml. Conversely, R did not affect the growth of normal dividing human peripheral blood mononuclear cells (PBMC) by exhibiting a large value of IC50 over 200 microg/ml. Accumulation of tumor cells at sub-G1 phase and the fragmentation of DNA, typical features of programmed cell death, were observed in a time and dose dependent manner. Scavenging of free radicals and anti-cancer activity (value of IC50) correlated closely with the quantities of polysaccharides (Spearman's rho=0.901 and -0.870, respectively). Taken together, our findings suggest that fraction R, obtained by SC-CO2 fluid extractive fractionation, showed strong scavenging ability and selectively inhibited the growth of colorectal and hepatocellular cancer cells by the process of apoptosis.


  Medicinal herbal extracts--renal friend or foe? Part two: herbal extracts with potential renal benefits.:

 In this second of two articles regarding the renal toxicities or benefits of medicinal herbs, herbs are reported as being 'potentially beneficial' to the kidneys if there is strong in vivo evidence of renal protection from toxic substances or drugs; potent, specific renal anti-oxidant effects; in vivo cancer antiproliferative effects specific to the kidneys; or in vivo evidence of being beneficial in renal disease or failure. Among the herbs, polyherbal formulae and fungi with potential renal benefits are Cordyceps sinensis, Sairei-to, Rheum spp., Salvia miltiorrhiza and its component, magnesium lithospermate B and others.

  Antitumour activity of cordycepin in mice.:

 SUMMARY 1. The antitumour effect of orally administered cordycepin, a component isolated from water extracts of Cordyceps sinensis, was examined in mice inoculated with B16 melanoma (B16-BL6) cells. 2. B16-BL6 (1 x 10(6)) cells were inoculated subcutaneously into the right footpad of mice. At 2 weeks after the cell inoculation, the enlarged primary tumour lump was weighed. Cordycepin (0, 5 and 15 mg/kg per day) was administered orally to the mice for 2 weeks from the date of tumour inoculation. Cordycepin (15 mg/kg per day) significantly reduced by 36% the wet weight of the primary tumour lump compared to that of the untreated control mice, without any loss of bodyweight or systemic toxicity. 3. Cordycepin (15 mg/kg per day) administered orally for 2 weeks inhibited the tumour enlargement in the right thigh inoculated with B16-BL6 cells premixed with extracellular matrix (Matrigel). 4. These results indicate that orally administered cordycepin inhibits melanoma cell growth in mice with no adverse effects.

  The traditional Chinese medicine Cordyceps sinensis and its effects on apoptotic homeostasis.:

 Cordyceps sinensis is a medicinal fungus of Traditional Chinese Medicine. While there are a wide range of reported uses of Cordyceps sinensis in the literature, the reports that extracts of this fungus may alter apoptotic homeostasis are most intriguing. However, there are significant challenges regarding research surrounding Cordyceps sinensis, such as the difficulty identifying the various species of Cordyceps and the many conflicting reports of pharmacological function in the literature. In this review we outline what is known about the ability of Cordyceps sinensis to alter apoptotic homeostasis, attempt to reconcile the differences in reported function, identify the challenges surrounding future Cordyceps sinensis research, and delineate options for overcoming these critical hurdles.

  Studies on anamorph of Cordyceps sinensis (Berk) from Naqu Tibet.:

 OBJECTIVE: To isolate and determine the strain of anamorph of Cordyceps sinensis collected from Naqu Tibet. METHOD: Isolating the strains of anamorph of Cordyceps sinensis collected from Baqing Shuoxian, Biru Counties by means of the ascope, tissue, ossified larva and body liquid. RESULT: Same strain of anamorph of Cordyceps sinensis was obtained with 4 different methods. CONCLUSION: The strain of Hirsutella sinensis is the anamorph of C. sinensis from Naqu Tibet.
 


  Antifatigue and antistress effect of the hot-water fraction from mycelia of Cordyceps sinensis.:

 This study was conducted to investigate the chemical component of the hot water (HW) fraction of mycelia of Cordyceps sinensis and its antifatigue and antistress effect against a stimulus in vivo using rats and mice. The growth of mycelia reached a maximum level of 31.6 g/l after 120 h of incubation. The main chemical composition of the HW fraction of mycelia of C. sinensis was found to be carbohydrate (78.9%) with 5% moisture. The swimming endurance capacity of mice orally administered with the HW fraction (150 and 300 mg/kg/d, respectively) was significantly prolonged from 75 to 90 min with a lessening of fatigue. When the HW fraction (150 mg/kg/d) was given to rats for 8 d including a 48 h stress period, the weight changes of the adrenal gland, spleen, thymus, and thyroid, which is an index of stress, were suppressed. The HW fraction also significantly inhibited the increase in total cholesterol and the decrease in alkaline phosphatase levels as biochemical parameters of immobilization stress in rats.

  Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism.:

 AIM: To investigate the inhibitive effect and its possible mechanism of Cordyceps Sinensis (CS) on CCl(4)-plus ethanol-induced hepatic fibrogenesis in experimental rats. METHODS: Rats were randomly allocated into a normal control group, a model control group and a CS group. The latter two groups were administered with CCl(4) and ethanol solution at the beginning of the experiment to induce hepatic fibrosis. The CS group was also treated with CS 10 days after the beginning of CCl(4) and ethanol administration. All control groups were given corresponding placebo at the same time. At the end of the 9th week, rats in each group were humanely sacrificed. Blood and tissue specimens were taken. Biochemical, radioimmunological, immunohistochemical and molecular biological examinations were used to determine the level change of ALT, AST, HA, LN content in serum and TGFbeta(1), PDGF, collagen I and III expression in tissue at either protein or mRNA level or both of them. RESULTS: As compared with the model control group, serum ALT, AST, HA, and LN content levels were markedly dropped in CS group (86.0+/-34.4 vs 224.3+/-178.9, 146.7+/-60.2 vs 272.6+/-130.1, 202.0+/-79.3 vs 316.5+/-94.1 and 50.4+/-3.0 vs 59.7+/-9.8, respectively, P<0.05). Tissue expression of TGFbeta(1) and its mRNA, collagen I mRNA were also markedly decreased (0.2+/-0.14 vs 1.73+/-1.40, 1.68+/-0.47 vs 3.17+/-1.17, 1.10+/-0.84 vs 2.64+/-1.40, respectively, P<0.05). More dramatical drop could be seen in PDGF expression (0.87+/-0.43 vs 1.91+/-0.74, P<0.01). Although there was no statistical significance, it was still strongly suggested that collagen III mRNA expression was also decreased in CS group as compared with model control group (0.36+/-0.27 vs 0.95+/-0.65, P=0.0615). In this experiment, no significant change could be found in PDGF mRNA expression between two groups (0.35+/-0.34 vs 0.70+/-0.46, P>0.05). CONCLUSION: Cordyceps sinensis could inhibit hepatic fibrogenesis derived from chronic liver injury, retard the development of cirrhosis, and notably ameliorate the liver function. Its possible mechanism involves inhibiting TGFbeta(1) expression, and thereby, down regulating PDGF expression, preventing HSC activation and deposition of procollagen I and III.

  Resources and distribution of Cordyceps sinensis in Naqu Tibet.:

 This paper reported the resources and distribution of Cordyceps sinensis in Naqu district, the principally grown zone in Tibet. The investigation showed that the yearly yield of Cordyceps sinensis are 7000 kg, the distribution areas are Baqin, Suoxian, Biru, Jiali, Naqu and Nierong county at 30 degrees 20'-32 degrees 48' N, 92 degrees 0'-94 degrees 50' E. The rangs of vertical distribution from the elevation 5000 m to 4100 m; the ecological geographical distribution is affected mainly by vegetation, soil, temperature and humidity.


  Hypocholesterolemic effect of hot-water extract from mycelia of Cordyceps sinensis.:

 This study was conducted to investigate the hypocholesterolemic effect of the hot-water fraction (HW) from cultured mycelia of Cordyceps sinensis in a 5 l fermenter. The composition of HW was mainly carbohydrate (83.9%) and protein (11.8%) on a dry basis, and the carbohydrate of HW consisted of glucose, mannose, galactose, and arabinose in the molecular ratio of 1.0 : 0.8 : 0.5 : 0.1, respectively. In mice fed a cholesterol-free diet and those fed a cholesterol-enriched diet, body and liver weights were not significantly different from those of the controls. The serum total cholesterol (TC) of all mice groups administered HW (150 and 300 mg/kg/d, respectively) with the cholesterol-enriched diet decreased more than in the control group. Among the mice fed the cholesterol-enriched diet, HW also increased the high-density lipoprotein (HDL) cholesterol level, but decreased the very low-density lipoprotein plus low-density lipoprotein (VLDL+LDL) cholesterol level. The changes in HDL- and VLDL+LDL-cholesterol levels consequently decreased the atherogenic value. The results indicate that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol level. The 300 mg/kg dose had a significant effect on the serum TC level.

  Immunomodulatory and antitumour effects of an exopolysaccharide fraction from cultivated Cordyceps sinensis (Chinese caterpillar fungus) on tumour-bearing mice.:

 Cordyceps sinensis (Chinese caterpillar fungus) is a fungus parasitic on the larvae of Lepidoptera and has been considered to be a precious tonic food and herbal medicine since ancient times in China. Recently, some fungal strains have been isolated from the fruiting bodies of wild C. sinensis, and some of them have been reported to show the same properties as the natural product. In the present study, an EPSF (exopolysaccharide fraction) was prepared from cultivated C. sinensis and its effects on B16 melanoma-bearing mice were investigated. Three doses of EPSF were intraperitoneally administered every 2 days after the day of tumour-cell injection. The experiment was terminated on day 28. Phagocytosis of peritoneal macrophages and proliferation of spleen and thymus lymphocytes were assayed. The tumour metastatic foci on the lung and liver surface were checked. The expression of oncoprotein Bcl-2 in livers and lungs was assayed by a immunohistochemical method. The results showed that EPSF significantly enhanced the Neutral Red uptake capacity of peritoneal macrophages (60 mg/kg, P<0.01; 120 mg/kg, P<0.001) and spleen lymphocyte proliferation (60 mg/kg, P<0.05; 120 mg/kg, P<0.001) in B16-bearing mouse. The metastasis of B16 melanoma cells to lungs (120 mg/kg) and livers (30, 60 and 120 mg/kg) was significantly inhibited by EPSF. Moreover, EPSF decreased the levels of Bcl-2 in the lungs (120 mg/kg) and livers (30, 60 and 120 mg/kg). These results suggest that EPSF has immunomodulatory function and antitumour activity.

  Pharmacological basis of 'Yin-nourishing' and 'Yang-invigorating' actions of Cordyceps, a Chinese tonifying herb.:

 Cordyceps sinensis (Berk.) Sacc. (Cordyceps), a popular Chinese tonifying herb, was revered for being both 'Yin-nourishing' and 'Yang-invigorating' in Chinese medicine. In order to establish the pharmacological basis for the 'Yin-nourishing' and 'Yang-invigorating' action of Cordyceps, the effects of wild and cultured Cordyceps on concanavalin A (Con A)-stimulated splenocytes, an in vitro bioassay for 'Yin-nourishment', and myocardial ATP generation capacity, an ex vivo bioassay for 'Yang-invigoration', were investigated in mice. The results indicated that methanolic extracts of wild and cultured Cordyceps enhanced both the Con A-stimulated splenocyte proliferation in vitro and myocardial mitochondrial ATP generation ex vivo in mice, with no significant difference in potency of action between the two types of Cordyceps. While the immuno-potentiating effect was associated with the increase in interleukin II production, the stimulation of myocardial ATP generation was paralleled by an enhancement in mitochondrial electron transport. When compared with typical 'Yin' and 'Yang' tonifying Chinese herbs, Cordyceps was found to possess both 'Yin-nourishing' and 'Yang-invigorating' activities, with a lower potency in both modes of action. The pharmacological characterization of Cordyceps by means of contemporary bioassays is consistent with the time-honored clinical observation from Chinese herbalists.

  An experimental study on anti-aging action of Cordyceps extract.:

 OBJECTIVE: To investigate anti-aging effect and mechanism of Cordyceps extract(CSE) on aged mice induced by D-galactose. METHOD: The aged mice were induced by D-galactose. Meanwhile, they were treated with three doses of CSE. Then the ability of learning and memory, the activity of antioxidase in the different tissue, the contents of MDA of brain and liver were measured after 6 weeks. RESULT: CSE could significantly increase the ability of learning and memory, improve the activity of SOD of red blood cells, brain and liver, the activity of Na(+) -K(+) -ATPE of brain, the activity of CAT and GSH-Px of blood, and remarkably decrease the activity of MAO of brain and the contents of MDA of brain and liver. CONCLUSION: CSE has good anti-aging effects on the aged mice, which is probably due to effects of improving antioxidation and removing free radicals.
 


  Determination of adenosine and cordycepin in Cordyceps sinensis and C. militarris with HPLC-ESI-MS.:

 OBJECTIVE: HPLC-ESI-MS to establish a method for simultaneous determination of adenosine and cordycepin in Cordyceps sinensis and C. militarris. METHOD: HPLC-ESI-MS method. An electrospray ionization (ESI) interface and selective ion monitoring (SIM) mode were used. The analytical column was a 2.0 mm x 150 mm Shimadzu VP - ODS column and the mobile phase was water (94%), methanol (5%) and formic acid (1%). 2-Chloroadenosine was used as internal standard for this assay. RESULT: The regression equations and coefficient were Y = 0.134 6X + 0.001 29 (r = 0.998 4) for adenosine, Y = 0.216 4X + 0.021 5 (r = 0.999 1) for cordycepin. The liner range was 0.5 approximately 124.5 microg x mL(-1) and 0.5 approximately 136.5 microg x mL(-1) for adenosine and cordycepin, respectively. The average recoveries of adenosine and cordycepin were 95.8% and 98.1%, respectively. CONCLUSION: This method is highly sensitive, fast and selective, which can be used for the determination of nucleosides in C. sinensis and its substitutes. This method can also be applied for the quality control of above herbs.

  Cordyceps Sinensis (CordyMax Cs-4) supplementation does not improve endurance exercise performance.:

 It is purported that supplementation with Cordyceps Sinensis (CordyMax Cs-4) will improve oxidative capacity and endurance performance. The intent of this investigation was to examine the effects of CordyMax Cs-4 supplementation on VO<(2peak,) ventilatory threshold, and endurance performance in endurance-trained cyclists. Twenty-two male cyclists participated in 5 weeks of supplementation with CordyMax Cs-4 tablets (3 g/d). Training intensity was maintained by weekly documentation and reporting throughout the 5-week period. Subjects completed a VO(2peak) test and work-based time trial prior to and following the supplementation period. VO(2peak) was similar within and between placebo (PLA) and treatment (CS) groups prior to (59.9 +/- 5.9 vs. 59.1 +/- 5.4 ml/kg/min, respectively) and following (60.1 +/- 5.5 vs. 57.1 +/- 5.8 ml/kg/min, respectively) the supplementation period. Ventilatory threshold (VT) was measured at 72 +/- 10% of VO(2peak) in P and T prior to supplementation and did not change in either group following the supplementation. PLA completed the time trial in 61.4+/- 2.4 min compared to 62.1+/- 4.0 min in T. Time trial measurements did not differ between groups, nor did they change in response to supplementation. It is concluded that 5 weeks of CordyMax Cs-4 supplementation has no effect on aerobic capacity or endurance exercise performance in endurance-trained male cyclists.

  The effects of cordyceps sinensis supplementation on endurance and strength exercises.:

 CS (Cordyeeps sinensis) is a time-honored tonic food and Chinese herbal medicine. The purposes of this study are: (1) to determine the blood levels of luteinzing hormone (LH) and testosterone after taking CS. (2) to investigate the effects of CS supplementation on metabolic substrates, respiratory compositions and endurance performance, and (3) to investigate the effects of CS supplementation and heavy-resistance training on body composition, blood biochemistry, and total maximal muscle strength. Subjects ingested 3 capsules (400mg CS/capsule) twice a day. The results showed no significant difference of LH concentration in plasma before and after supplementation. After supplementation of CS, the testosterone increased 21.0 % for 21 days, and increased 11.5 % for 28 days as compared with the values of pre-supplementation. Four weeks of CS supplementation, the subjects tend to use free fatty acid as fuel source during the endurance exercise. However, CS supplementation may not improve submaximal endurance exercise performance in our study. Eight weeks of CS supplementation combined with heavy-resistance training could significantly increase hemoglobin level and total maximal muscle strength.


  Mycelium cultivation, chemical composition and antitumour activity of a Tolypocladium sp. fungus isolated from wild Cordyceps sinensis.:

 AIMS: To examine and illustrate the morphological characteristics and growth kinetics of Cs-HK1, a Tolypocladium fungus, isolated from wild Cordyceps sinensis in solid and liquid cultures, and the major chemical constituents and antitumour effects of Cs-HK1 mycelium. METHODS AND RESULTS: The Cs-HK1 fungus was isolated from the fruiting body of a wild C. sinensis and identified as a Tolypocladium sp. fungus. It grew rapidly at 22-25 degrees C on a liquid medium containing glucose, yeast extract, peptone and major inorganic salts, with a specific growth rate of 1.1 day(-1), reaching a cell density of 23.0 g dw l(-1) in 7-9 days. Exopolysaccharides accumulated in the liquid culture to about 0.3 g l(-1) glucose equivalent. In comparison with natural C. sinensis, the fungal mycelium had similar contents of protein (11.7-microg) and carbohydrate (654.6-microg) but much higher contents of polysaccharide (244.2 mg vs 129.5 mg), adenosine (1116.8-microg vs 264.6 microg) and cordycepin (65.7 microg vs 20.8 microg) (per gram dry weight). Cyclosporin A, an antibiotic commonly produced by Tolypocladium sp., was also detected from the mycelium extract. The hot water extract of mycelium showed low cytotoxic effect on B16 melanoma cells in culture (about 25% inhibition) but significant antitumour effect in animal tests, causing 50% inhibition of B16 cell-induced tumour growth in mice. CONCLUSIONS: The Tolypocladium sp. fungus, Cs-HK1, can be easily cultivated by liquid fermentation. The mycelium biomass contained the major bioactive compounds of C. sinensis, and the mycelium extract had significant antitumour activity. SIGNIFICANCE AND IMPACT OF THE STUDY: The Cs-HK1 fungus may be a new and promising medicinal fungus and an effective and economical substitute of the wild C. sinensis for health care.

  Quality evaluation of Cordyceps through simultaneous determination of eleven nucleosides and bases by RP-HPLC.:

 A new RP-HPLC method has been developed for the simultaneous determination of 11 nucleosides and bases, including adenosine, cordycepin, cytidine, guanosine, inosine, thymidine, uridine, cytosine, guanine, thymine, and uracil in Cordyceps. Determination was achieved on a Zorbax 300SB C18 analytical column (4.6 x 250 mm id, 5 mm) using gradient elution with diode-array detection. All calibration curves showed good linearity (r2 > 0.9995) within the test ranges. The developed method was simple, rapid, and accurate, and showed good reproducibility for the quantification of 11 nucleosides and bases in natural and cultured Cordyceps with both intra- and inter-day variations of less than 1.8%. Furthermore, hierarchical clustering analysis based on the typical peaks of adenosine, cordycepin, and inosine in HPLC profiles from the 11 tested samples showed that natural and cultured Cordyceps were in different clusters, which could provide a means of discriminating between Cordyceps of different origins. Thus, adenosine, cordycepin, and inosine could be used as markers for quality control of Cordyceps.

  Separation and determination of selenium polysaccharide in enriched-Se cordyceps militaris.:

 In the present paper, the water soluble selenium polysaccharide was extracted, and isolated and purified preliminarily. The traditional method was used to extract selenium polysaccharide, which was extracted by water and sank by ethanol. The work also focused on the determination of the experiment conditions, optimizing the experiment conditions such as proportion of extract solution, extract temperature, extract times, proportion of ethanol, and standing time. The recovery of selenium polysaccharide under these conditions is 5.76%. Polysaccharide content in the powder is 46.6%, and selenium content is 92.3 mg x kg(-1).

  Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia.:

 Cordyceps sinensis, a well-known traditional Chinese medicine, possesses anti-tumor, immunostimulant and antioxidant activities; however, the identities of active components have not been determined. In our previous study using antioxidant activity-guided fractionation [Li et al., 2003. A polysaccharide isolated from Cordyceps sinensis, a traditional Chinese medicine, protects PC12 cells against hydrogen peroxide-induced injury. Life Sci. 73, 2503-2513], a polysaccharide of molecular weight approximately 210kDa was isolated from cultured Cordyceps mycelia by ion-exchange and sizing chromatography. The isolated polysaccharide, named CSP-1, which has strong anti-oxidation activity, contains glucose, mannose and galactose in the ratio of 1:0.6:0.75. In the present study, we demonstrated the hypoglycemic effect of CSP-1 on normal and alloxan-diabetic mice and streptozotocin (STZ)-diabetic rats. The basal glucose level did not differ significantly among the normal mice. CSP-1 (at 200 and 400mg/kg body wt./day for 7 days, p.o.), however, significantly reduced the blood glucose level by 12.0+/-3.2% and 22.5+/-4.7% in normal mice, respectively (p<0.05). When administered at a dose of higher than 200mg/kg body wt. daily for 7 days, CSP-1 produced a significant drop in blood glucose level in both STZ-induced diabetic rats and alloxan-induced diabetic mice. The serum insulin levels in diabetic animals were also increased by administration of CSP-1 (p<0.05). CSP-1 with hypoglycemic properties increased circulating insulin level in diabetic animals, which suggests that CSP-1 may stimulate pancreatic release of insulin and/or reduce insulin metabolism.
 


  Effect of various extracts and a polysaccharide from the edible mycelia of Cordyceps sinensis on cellular and humoral immune response against ovalbumin in mice.:

 In this study, the edible mycelia of Cordyceps sinensis (Berk.) Sacc. were sequentially extracted by petroleum ether, ethyl acetate, ethanol and ultrasonic water-bath (75 degrees C), and the water extract was further isolated by Sephadex G-100 to afford a petroleum ether extract (PE), ethyl acetate extract (EAE), ethanol extract (EE), glycoprotein (GP) and a purified polysaccharide (PS). In combination with component analysis, the isolated PS showed d-Glc, d-Man, l-Ara and d-Gal in a molar ratio of 8:90:1:1. The average molecular weight of PS was determined as approximately 8.3 x 10(4). The immunomodulatory potentials of these samples (PE, EAE, EE, GP and PS) at three dose levels on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA) were studied. ICR mice were immunized subcutaneously with 100 microg OVA alone or with 100 microg OVA dissolved in saline containing these samples (100, 200 or 400 microg) on days 1 and 15. Two weeks later (day 28), concanavalin A (Con A)- and OVA-stimulated splenocyte proliferation and OVA-specific antibody in serum were investigated. These samples, except for PS, significantly enhanced the Con A- and OVA-induced splenocyte proliferation in OVA-immunized mice at a suitable dose (p < 0.05 or p < 0.01). OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were significantly enhanced by these extracts and PS compared with the OVA control group (p < 0.05, p < 0.01 or p < 0.001).

  Effects of cordyceps sinensis alcohol extractive on serum interferon-gamma level and splenic T lymphocyte subset in mice with viral myocarditis.:

 AIM: To investigate the effects of early application of cordyceps sinensis alcohol extractive (CSAE) on myocardial injury, level of serum IFN-gamma and splenic T lymphocyte subset in murine viral myocarditis (VMC). METHODS: 100 male BALB/c mice were divided randomly into control group (CG), infectious group (IG) and CSAE therapy group (CTG). Mice in IG and CTG were infected with Coxsackie virus B3 (CVB3). The 14-day survival rates and myocardial histopathology were observed. Serum IFN-gamma level was detected by ELISA and splenic CD3+, CD4+, CD8+ T lymphocytes were detected by flow cytometry. RESULTS: Serum IFN-gamma level and the percentage of splenic T lymphocyte subset in IG were decreased significantly, and CD4+/CD8+ T cell ratio increased significantly as compared with those of CG. Myocardial lesions in CIG were attenuated, while the 14-day survival of mice 85% (vs IG 55%, P<0.05), serum IFN-gamma and the percentage of splenic CD3+, CD8+ T lymphocytes in CTG were significantly higher than those in IG. There were no significant differences of the percentage of T lymphocyte subset and CD4+/CD8+ T cell ratio between CTG and CG. CONCLUSION: CSAE plays an important protective role against viral-induced murine myocarditis by inducing IFN-gamma and regulating T lymphocyte.

  Comparison of protective effects between cultured Cordyceps militaris and natural Cordyceps sinensis against oxidative damage.:

 The Chinese herb DongChong-XiaCao originating from Cordyceps sinensis is widely used as a traditional medicine in China for treatment of a wide variety of diseases. The extracts of Cordyceps sinensis (CSE) and Cordyceps militaris (CME) are well-known for their biological effects. In the present study, the antioxidant efficiency of CME and CSE in protecting lipid, protein, and low-density lipoprotein (LDL) against oxidative damage was investigated. CME and CSE showed weakly inhibitory effect on liposome oxidation, that of CME being superior to that of CSE. As for the protein oxidation model system, the inhibitory effect of CME on protein oxidation was inferior to that of CSE. CME and CSE at 1.0 mg/mL showed 50.5 and 67.1% inhibition of LDL oxidation, respectively. The contents of bioactive ingredients cordycepin and adenosine in CME are higher than those of CSE; however, both cordycepin and adenosine showed no significant antioxidant activity as determined by the Trolox equivalent antioxidant capacity method. Polyphenolic and flavonoid contents are 60.2 and 0.598 microg/mL in CME and 31.8 and 0.616 microg/mL in CSE, respectively, which may in part be responsible for their antioxidant activities. In addition, a polysaccharide present in CME and CSE displayed antioxidant activity, which suggested that the activity might be derived partly from polysaccharides of CME and CSE. The tendency to scavenge the ABTS(*)(+) free radical and the reducing ability of CME and CSE display concentration-dependent manners, suggesting that CME and CSE may be potent hydrogen donators. On the basis of the results obtained, the protective effects of CME and CSE against oxidative damage of biomolecules are a result of their free radical scavenging abilities.

  A comparative study on the production of exopolysaccharides between two entomopathogenic fungi Cordyceps militaris and Cordyceps sinensis in submerged mycelial cultures.:

 AIMS: The present study comparatively investigates the optimal culture conditions for the production of exopolysaccharides (EPS) and cordycepin during submerged mycelial culture of two entomopathogenic fungi Cordyceps militaris and Cordyceps sinensis. METHODS AND RESULTS: Fermentations were performed in flasks and in 5-l stirred-tank fermenters. In the case of C. militaris, the highest mycelial biomass (22.9 g l(-1)) and EPS production (5 g l(-1)) were achieved in a medium of 40 g l(-1) sucrose, 5 g l(-1) corn steep powder at 30 degrees C, and an initial pH 8.0. The optimum culture conditions for C. sinensis was shown to be (in g l(-1)) 20 sucrose, 25 corn steep powder, 0.78 CaCl2, 1.73 MgSO4.7H2O at 20 degrees C, and an initial pH 4.0, where the maximum mycelial biomass and EPS were 20.9 and 4.1 g l(-1) respectively. Cordycepin, another bioactive metabolite, was excreted at low levels during the early fermentation period (maximum 38.8 mg l(-1) in C. militaris; 18.2 mg l(-1) in C. sinensis). CONCLUSIONS: The two fungi showed different nutritional and environmental requirements in their submerged cultures. Overall, the concentrations of mycelial biomass, EPS and cordycepin achieved in submerged culture of C. militaris were higher than those of C. sinensis. SIGNIFICANCE AND IMPACT OF THE STUDY: C. militaris and C. sinensis are representative insect-born fungi which have been longstanding and widely used as traditional medicines in eastern Asia. Comparative studies between two fungi are currently not available and this is the first report on the optimum medium composition for submerged culture of C. sinensis.


  Cordyceps sinensis mycelium induces MA-10 mouse Leydig tumor cell apoptosis by activating the caspase-8 pathway and suppressing the NF-kappaB pathway.:

 Cordyceps sinensis has been used as nutritious food and medicine in Chinese society. CS can inhibit tumor growth and induce tumor cell apoptosis. CS induced MA-10 mouse Leydig tumor cell death, but the anti-tumor mechanisms are not fully understood. Thus, the aim of this study was to investigate the apoptotic effect of CS on MA-10 cells and determine the molecular mechanism. CS (2-10 mg/ml) was added to MA-10 cells at different time scales (0-24 h). The condensation of DNA chromatin and apoptotic nuclear fragmentation increased in CS-treated MA-10 cells. Western blot analysis showed that 3 hours of CS treatment caused an increase in caspase-3 and -8 expressions only, which provided further evidence for the involvement of caspase-3 and -8 in CS-induced MA-10-cell apoptosis. CS blocked NF-?B protein expression in a dose-dependent relationship. CS induces MA-10 cell apoptosis by activating caspase-8-dependent and caspase-9-independent pathways and downregulating NF-?B protein expression.

  Pharmacological actions of Cordyceps, a prized folk medicine.:

 Cordyceps species, including C. sinensis, C. militaris, C. pruinosa and C. ophioglossoides, are prized traditional medicinal materials. The aim of this article is to review the chemical constituents and pharmacological actions of Cordyceps species. The chemical constituents include cordycepin (3'-de-oxyadenosine) and its derivatives, ergosterol, polysaccharides, a glycoprotein and peptides containing alpha-aminoisobutyric acid. They include anti-tumour, anti-metastatic, immunomodulatory, antioxidant, anti-inflammatory, insecticidal, antimicrobial, hypolipidaemic, hypoglycaemic, anti-ageing, neuroprotective and renoprotective effects. Polysaccharide accounts for the anti-inflammatory, antioxidant, anti-tumour, anti-metastatic, immunomodulatory, hypoglycaemic, steroidogenic and hypolipidaemic effects. Cordycepin contributes to the anti-tumour, insecticidal and antibacterial activity. Ergosterol exhibits anti-tumour and immunomodulatory activity. A DNase has been characterized.

  Antioxidant and memory enhancing effects of purple sweet potato anthocyanin and cordyceps mushroom extract.:

 The effects of purple sweet potato anthocyanin (SPA) and Cordyceps mushroom extract (CME) on lipid peroxidation, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and cognitive deficits were examined. Both SPA and CME exhibited DPPH radical scavenging activities with similar potency. In contrast, only SPA was shown to effectively inhibit lipid peroxidation initiated by Fe2+ and ascorbic acid in rat brain homogenates. Furthermore, SPA markedly enhanced cognitive performance, assessed by passive avoidance test in ethanol-treated mice. Combined treatments with SPA and CME did not significantly influence the effects of SPA alone. These results demonstrate that anthocyanin prepared from purple sweet potato exhibits memory enhancing effects, which may be associated with its antioxidant properties.
 

  A polysaccharide isolated from Cordyceps sinensis, a traditional Chinese medicine, protects PC12 cells against hydrogen peroxide-induced injury.:

 Cordyceps sinensis, a well-known traditional Chinese medicine, possesses activities in anti-tumour, anti-oxidation and stimulating the immune system; however, the identity of active component(s) is not determined. By using anti-oxidation activity-guided fractionation, a polysaccharide of molecular weight approximately 210 kDa was isolated from cultured Cordyceps mycelia by ion-exchange and sizing chromatography. The isolated polysaccharide, having strong anti-oxidation activity, contains glucose, mannose and galactose in a ratio of 1 : 0.6 : 0.75. The pre-treatment of isolated polysaccharide on the cultured rat pheochromocytoma PC12 cells shows strong protective effect against hydrogen peroxide (H(2)O(2))-induced insult. Treatment of the cells with the isolated polysaccharide at 100 microg/ml prior to H(2)O(2) exposure significantly elevated the survival of PC12 cells in culture by over 60%. In parallel, the H(2)O(2)-induced production of malondialdehyde in cultured cells was markedly reduced by the polysaccharide treatment. Moreover, the pre-treatment of the isolated polysaccharide significantly attenuated the changes of glutathione peroxidase and superoxide dismutase activities in H(2)O(2)-treated cells in a dose-dependent manner. This is the first report in identifying a polysaccharide from Cordyceps, which protects against the free radical-induced neuronal cell toxicity.

  Hot-water extract from mycelia of Cordyceps sinensis as a substitute for antibiotic growth promoters.:

 Broiler chicks were orally dosed with a hot-water extract of mycelia from Cordyceps sinensis (CS-HW) to assess possible substitution of Avilamycin as an antibiotic growth promoter (AGP). The growth performance (body weight gain and survivability) and the health index (the microflora in the small intestines and the antibody titer to Newcastle disease virus) of chicks were significantly improved in the CS-HW (600 mg/kg diet) and the Avilamycin (20 mg/kg diet) fed group in comparison with the control group (p < 0.05). The Avilamycin-fed group and the CS-HW-fed group had similar growth performances but the latter gave a better microbial flora in the small intestines. These results indicate that CS-HW enhances the physiological activity in chicks and can be used as a substitute for AGPs.


  Study on the biology of adults parasite of Cordyceps sinensis, Hepialus biruensis.:

 OBJECTIVE: To supply the basis of the breeding the host of parasite of Cordyceps sinensis for it's natural culturing, by studying the biology of the host of parasite of C. sinensis, Hepialus biruensis. METHOD: The host of parasite was collected in field, eclosion, mating and spawning in the different conditions were made, and it's biology and the regularity of the growth and development were observed. RESULT AND CONCLUSION: In the natural condition, H. biruensis has the rate of eclosion, 42.3%, and the sex ratio, 1:0.86, and it's lifespan is 2-5 days. It has the rate of eclosion, 67.4%, in the constant temperature. At the 18 degrees C, H. biruensis has the highest rate of mating and spawning, 92% and 98%, and its rate of mating and spawning varies in the different temperature conditions. The male moth cherishes average 814.4 eggs and lays 607.2 eggs. In the open country, the optimum air relative humidity for mating and laying eggs is 75%-90%, while indoors, the optimum air relative humidity is 78%.

  Activation of macrophages and the intestinal immune system by an orally administered decoction from cultured mycelia of Cordyceps sinensis.:

 The effects of an orally administered hot-water extract (HW) from cultured mycelia of Cordyceps sinensis on the activation of macrophages and the intestinal immune system were studied in mice. The general composition of HW was 83.9% carbohydrate, 11.8% protein, 1.9% lipid and 2.4% ash, and the carbohydrates were mainly composed of glucose, mannose, galactose and arabinose (molar ratio of 1.0:0.8:0.5:0.1). HW stimulated the activation (1.7-fold of the saline control) of macrophages and IL-6 production (1.5-fold) at 2.0 g/kg/day. Analyzing the culture supernatant of Peyer's patch cells from C3H/HeJ mice that had been fed with HW at 1.0 g/kg/day for 7 days indicated that the bone marrow cells had significantly proliferated (1.9-fold). In addition, the amounts of GM-CSF and IL-6 in the culture supernatant of Peyer's patch cells at the same dose were significantly increased (1.8-fold and 2.2-fold, respectively). These results indicate that an oral administration of HW may modulate IL-6 production by the activation of macrophages, and also enhance the secretion of hematopoietic growth factors such as GM-CSF and IL-6 from Peyer's patch cells. Since such cytokines as GM-CSF and IL-6 from Peyer's patch cells act on the systemic immune system, it can be assumed that orally administered HW modulated not only the local but also systemic immune system.

  Effect of Cordyceps sinensis on inhibiting systemic lupus erythematosus in MRL 1pr/1pr mice (correction of rats).:

 OBJECTIVE: To study the effect of Cordyceps sinensis on inhibiting systemic lupus erythematosus (SLE) in MRL 1pr/1pr rats. METHODS: The evalutions of lymphnoditis, proteinuria, kidney function and plasma antibody were adopted in MRL 1pr/1pr rats. RESULTS: Cordyceps sinensis could inhibit lymphadenectasis, induce the level of proteinuria and anti-ds-DNA antibody in plasma, and improve kidney function in SLE rats. CONCLUSION: Codyceps sinensis played an role on SLE rats.

  Effects of Cordyceps sinensis on testosterone production in normal mouse Leydig cells.:

 The stimulatory effect of Cordyceps sinensis (CS) on MA-10 mouse Leydig tumor cell steroidogenesis was previously demonstrated in our laboratory. In the present studies, we further determined the effect of CS on steroidogenesis in purified normal mouse Leydig cells. Different concentrations of CS (0.1-10 mg/ml) were added to Leydig cells without or with human chorionic gonadotropin (hCG) (50 ng/ml), and the steroid production was determined by radioimmunoassay (RIA). The results illustrated that CS stimulated normal mouse Leydig cell steroidogenesis in a dose-dependent relationship. CS at 3 mg/ml significantly stimulated testosterone production (p<0.05). Concerning the temporal relationship, CS at 3 mg/ml stimulated maximal testosterone production between 2 to 3 hr. Interestingly, hCG-stimulated testosterone productions were suppressed by CS in a dose-dependent relationship. CS also reduced dbcAMP-stimulated testosterone productions, which indicated that CS affected signal transduction pathway of steroidogenesis after the formation of cyclic AMP. Moreover, cycloheximide inhibited CS-treated mouse Leydig cell testosterone production, suggesting that new protein synthesis was required for CS-stimulated steroidogenesis.

  A preliminary study on alternation of generations of Cordyceps sinensis (Berkey) Sacc.:

 The insect pathogeny of parasitic hepialus by Cordyceps sinensis is, reported in this paper. The infestation of hepialus larvae by Cordyceps sinensis, growth and reproduction of hypha body in the hemolymph of host larvae, growth of stroma, maturity of hymenium and the abjection and germination of ascospores were observed.


  Cordyceps sinensis and its fractions stimulate MA-10 mouse Leydig tumor cell steroidogenesis.:

 The effects of Cordyceps sinensis (CS) and its extracted fractions on steroidogenesis in MA-10 cells were determined. Different concentrations of CS and 3 fractions of CS (F1, a water-soluble polysaccharide; F2, a water-soluble protein; and F3, a poorly water-soluble polysaccharide and protein) were added to MA-10 mouse Leydig tumor cells with or without human chorionic gonadotropin (hCG), and the production of steroid and the expression of steroidogenic acute regulatory protein (StAR) were examined. The results showed that CS alone (2-10 mg/mL) stimulated MA-10 cell progesterone production in a dose-dependent relationship. Fractions F1 and F3 (2-10 mg/mL) also had significant (P < .05) stimulatory effects on MA-10 cell steroidogenesis with a dose-dependent relationship. However, fraction F2 did not have an effect on MA-10 cells. CS and F3, but not F1, significantly induced more steroid production in hCG-stimulated MA-10 cells (P < .05). As a temporal relationship, F1 and F3 (2 mg/mL) maximally stimulated progesterone production between 1 and 3 hours after stimulation in MA-10 cells. In addition, CS and F3 significantly enhanced MA-10 cell StAR protein expression, which indicates that CS and F3 may use a cyclic adenosine monophosphate signal transduction pathway to activate MA-10 Leydig cell steroidogenesis in a manner to that of luteinizing hormone.

  CordyMax Cs-4 improves steady-state bioenergy status in mouse liver.:

 OBJECTIVE: To evaluate effects of CordyMax Cs-4, a mycelial fermentation product of Cordyceps sinensis, on energy metabolism. DESIGN: An in vivo pharmacology study using 31P nuclear magnetic resonance (NMR) spectroscopy. SUBJECTS AND STUDY INTERVENTIONS: Adult male C57-BL/6 mice were given an aqueous extract of CordyMax, 200 or 400 mg/kg per day or placebo for 7 days. OUTCOME MEASUREMENTS: Using 31P-NMR spectroscopy to measure cellular triphosphates and inorganic phosphate, expressed as a ratio to a reference peak, and calculate tissue pH. RESULTS: Steady-state beta adenosine triphosphate (ATP) increased in the liver of mice that received CordyMax (200 or 400 mg/kg per day) for 7 days, by 12.3% +/- 0.8% and 18.4% +/- 0.9%, respectively, compared to placebo controls (both p < 0.001), suggesting a higher hepatic bioenergy status in CordyMax-treated animals. Hepatic inorganic phosphate (Pi) decreased by 24.5% +/- 0.9% and 17.6% +/- 1.7% in the two treatment groups, respectively, compared to placebo controls (p < 0.001). The ratio of beta-ATP:Pi increased by 47.7% +/- 1.6% and 41.4% +/- 2.4%, respectively, in the treatment groups (both p < 0.001 compared to placebo). After discontinuation of CordyMax for 7 days, beta-ATP and Pi returned towards baseline. CONCLUSION: CordyMax is effective in improving bioenergy status in the murine liver, suggesting a mechanism underlying the known clinical effectiveness of CordyMax in alleviating fatigue and improving physical endurance, especially in elderly subjects.

  Anti-oxidation activity of different types of natural Cordyceps sinensis and cultured Cordyceps mycelia.:

 Cordyceps, one of the well-known traditional Chinese medicines, consists of the dried fungus Cordyceps sinensis growing on the larva of the caterpillar. It is commonly used for the replenishment of body health. One of the known pharmacological effects is its anti-oxidation activity. However, there is a great variation of the quality in different sources of Cordyceps. Here, the water extracts of various sources of natural C. sinensis and cultured Cordyceps mycelia were analyzed for their anti-oxidation activity by using three different assay methods such as the xanthine oxidase assay, the induction of hemolysis assay and the lipid peroxidation assay. The results showed that Cordyceps, in general, possesses a strong anti-oxidation activity in all assays tested. However, both natural and cultured Cordyceps showed the lowest inhibition in the lipid peroxidation when compared with the other two assay methods. The cultured Cordyceps mycelia had equally strong anti-oxidation activity as compared to the natural Cordyceps. Besides, the anti-oxidation activities were increased to 10-30 folds in the partially purified polysaccharide fractions from the cultured Cordyceps mycelia, which suggested that the activity could be derived partly from Cordyceps polysaccharides.


  Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis.:

 Cordyceps sinensis is a herb medicine in China for the treatment of general debility after sickness and for persons of advanced age. In the present study, cordyceps sinensis was extract by phosphate buffer saline (PBS) and dialyzed overnight against PBS using a membrane cut off at 3,500 dalton molecular weight. The resulting macromolecule fraction (defined as CS) was assayed in anesthetized rats for hypotensive effects and in isolated aorta for vasorelaxant effects. Intravenous injection of CS (8,16, 24 and 32 mg/kg, respectively) suppressed significantly the mean arterial pressure (MAP) in a dose-dependent manner. 32 mg/kg of CS induces the maximal hypotensive response with a 58 +/- 4 mm Hg (from 107 +/- 6 to 49 +/- 3 mm Hg) change in MAP and a over 45 min action duration. In aortic rings precontracted with phenylephrine treatment with CS between 0.5 and 500 microg/ml induced dose dependent relaxation. Maximal vasorelaxant response evoked by 150 microg/ml CS was 68.9 +/- 7.3%. Furthermore, CS-induced vasorelaxation is mediated by the endothelium possibly by stimulating the release of the nitric oxide and endothelium-derived hyperpolarizing factor. In conclusion, the present study revealed that presence of a constituent in CS which reduces MAP by relaxing the vascular beds directly. However, the effect may be caused by a single active ingredient or by the combined action of many active agents found in the extract.

  Inhibitory effects of water extracts from fruiting bodies of cultured Cordyceps sinensis on raised serum lipid peroxide levels and aortic cholesterol deposition in atherosclerotic mice.:

 We investigated the effects of the water extracts of the fruiting bodies of cultured Cordyceps sinensis (WECS) on lipid metabolism in mice fed an atherogenic diet. WECS was orally administered at doses of 50, 100 and 200 mg/kg/day for 12 weeks. WECS showed no toxic effects on the growth rate, liver or kidney weights of the mice. Mice fed the atherogenic diet showed marked increases in serum lipid and lipid peroxide levels and also aortic cholesterol levels, particularly cholesteryl ester level, a major lipid constituent in atherosclerotic lesions. WECS significantly suppressed the increased serum lipid peroxide level but not other lipid levels in a dose-dependent manner. WECS also suppressed the increased aortic cholesteryl ester level in a dose-dependent manner. These results suggest that WECS prevents cholesterol deposition in the aorta by inhibition of LDL oxidation mediated by free radicals rather than by reduction in serum lipid level. WECS may exert beneficial effects on the formation of the atherosclerotic lesion induced by oxidative stress with few side effects.

  Antioxidant activity of the extracts from fruiting bodies of cultured Cordyceps sinensis.:

 Cordyceps sinensis is one of the most valued herbs in traditional Chinese medicine. We investigated the antioxidant activities of the cultured fruiting bodies of Cordyceps sinesis. The water and ethanol extracts of Cordyceps sinensis were found to possess a potent antioxidant activity. The scavenging effects of the extracts on superoxide were very weak, but the extracts moderately inhibited malondialdehyde formation via hydroxyl radical induced by SIN-1, a peroxynitrite generator. Of the extracts examined, the hot water extract (70 degrees C for 5 min) showed the greatest oxygen free radical scavenging activity. Also, when low-density lipoprotein (LDL) was incubated with macrophages in the presence of CuCl2 (1 microM), the hot water extract showed a strong inhibitory effect against lipid peroxidation in the medium and consequent accumulation of cholesteryl ester in macrophages. Their activities were comparable to that of authentic Cu/Zn SOD. These results suggest that the extracts of cultured Cordyceps sinensis possess potent antioxidant and anti-lipid peroxidation activities and inhibit accumulation of cholesteryl ester in macrophages via suppression of LDL oxidation.

  The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis: part II.:

 Cordyceps sinensis (Berk.) Sacc. is a time-honored tonic food and herbal medicine in China, where recent research has shown that many of its traditional uses may be viewed from the basis of pharmacological activities. The ongoing exploration of C. sinensis in its wild form and cultured, fermented mycelial products derived from it, are reviewed from English and Chinese literature. Part II concludes the series with a review of C. sinensis in preclinical in vitro and in vivo studies, and open-label and double-blinded clinical trials on the respiratory, renal, hepatic, cardiovascular, immunologic, and nervous systems, and its effects on cancer, glucose metabolism, inflammatory conditions, and toxicological studies. In Part I, which appeared in the Fall 1998 issue of this journal (4(3):289-303), we discussed the effects of C. sinensis on antisenescence, endocrine and sexual functions, atherosclerosis, hyperlipidemia, and free radicals.
 


  Cordyceps sinensis in protection of the kidney from cyclosporine A nephrotoxicity.:

 To explore the protective effect of cordyceps sinensis (CS) on cyclosporine A nephro-toxicity (CsA-Nx) and the possible mechanism, we studied the kidney changes induced by CsA in rats by light microscopy (LM), electronic microscopy (EM) and morphometrical analysis. At the 15th day after receiving CsA, prominent vacuolation and necrosis were noted microscopically in proximal tubular cells and mitochondria swelling electronmicroscopically. Morphometrical study showed that the epithelial areas of both proximal and distal tubules in the CS group were larger than those of the control group. There were obvious vacuolation (90%) and necrosis in proximal tubular cells at different stages of chronic CsA-Nx. Interstitial edema with mild fibrosis was observed. Mitochondria abnormality was seen electronmicroscopically. Morphometrical analysis showed that the epithelial cell areas of tubules and glomeruli were smaller in the CsA group than those in the CS group. Both acute and chronic experiments showed that CS could protect the kidney from CsA-Nx and ameliorate the glomerular and interstitial injuries.

  A pharmacological analysis of the amino acid components of Cordyceps sinensis Sacc.:

 An artificial complex of amino acids (C I) was made by mixing 18 synthetic amino acids, according to the kinds and contents the amino acid contained in the natural Cordyceps sinensis Sacc., It showed the same sedative action as the natural C. sinensis, as indicated by the spontaneous activity inhibition in mice (photocell method). However, the action of commercial complex amino acid injection (12 X, total amino acid components are similar to C I) was more attenuated than that of C I. Comparing amino acid components of 12 X with C I, the latter was found to contain 5 times as much glutamic acid, tryptophan and tyrosine as those of 12 X. Another artificial amino acid complex (C II) consisting of the above mentioned 3 amino acids, also showed the same sedative action. This suggests that tryptophan is the principal component by orthogonal test. However, C II did not enhance the phagocytic action of mononucleophagocyte as the natural C. Sinensis did in the clear rate test of carbon granule from mice serum.

  Antiarrhythmic effects of Cordyceps sinensis (Berk.) Sacc.:

 The administration of 65% alcohol extracts of Cordyceps sinensis can counteract the arrhythmias induced by aconitine or BaCl2 in rats, and increase the tolerant dose of ouabain to produce the arrhythmias in guinea pigs. The drug can reduce the heart rate of anesthetic rats, decreasing the contractility of isolated papillary muscle or atria in guinea pigs, but showing no effect on the automatic rhythmicity and the functional refractory period of the atria.

  Lei J, et al. Pharmacological Study on Cordyceps sinensis (Berk.) Sacc. and ze-e Cordyceps. Chung Kuo Chung Yao Tsa Chih. Jun1992;17(6):364-66.:

 The Ze-e Cordyceps is similar to the Cordyceps sinensis in such pharmacological actions as calming, enduring hypoxia, dilating trachea, male sex hormone action, antiphlogistic and toxicity, etc. It is thus suggested that the Ze-e Cordyceps may be used place of the Cordyceps sinensis in clinical practice.

  Effect of Jinshuibao Capsule on the Immunological Function of 36 Patients with Advanced Cancer. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. Aug1995;15(8):476-78.:

 Jinshuibao Capsule (JSBC), produced by Jiangxi Jinshuibao pharmaceutical Company Limited, possesses the similar active principles and pharmacological activity with those of Cordyceps sinensis. The effect of JSBC on the immunological function of 36 patients with advanced cancer showed that it could restore cellular immunological function, improve quality of life, but had no significant effect on humoral immunological function. The results suggested that JSBC could be used as adjuvant drug in advanced cancer.

  Effect of Cordyceps sinensis on the Proliferation and Differentiation of Human Leukemic U937 Cells. Life Sci. 1997;60(25):2349-59.:

 Cordyceps sinensis is a herb medicine with antitumor activity capable of suppressing the growth of mouse Sarcoma 180 in vivo. In the present study, we have isolated polysaccharide fraction of Cordyceps sinensis (PSCS) and investigated its effect on the proliferation and differentiation of human leukemic U937 cells using an in vitro culture system. Our results showed that the conditioned medium from PSCS (10 microg/ml)-stimulated blood mononuclear cells (PSCS-MNC-CM) had an activity that could significantly inhibit the proliferation of U937 cells resulting in a growth inhibition rate of 78-83%. Furthermore, PSCS-MNC-CM treatment induced about 50% of the cells differentiating into mature monocytes/macrophages expressing nonspecific esterase (NSE) activity and the surface antigens of CD11b, CD14, and CD 68. Yet, the differentiated U937 cells also had functions of phagocytosis and superoxide production. However, PSCS alone or normal MNC-CM had no such effects. The levels of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)- 1 were very low in normal MNC-CM, and they were greatly increased in MNC-CM prepared with PSCS stimulation. Antibody neutralization studies further revealed that the tumoricidal and differentiating effects of PSCS-MNC-CM were mainly derived from the elevated cytokines, especially IFN-gamma and TNF-alpha. These two cytokines acted synergistically on inhibiting cell growth and inducing differentiation of the target U937 cells.


  Antitumor Activity of an Extract of Cordyceps sinensis (Berk.) Sacc. against Murine Tumor Cell Lines. Jpn J Exp Med. Aug1989;59(4):157-61.:

 A warm water-extract (ECS) prepared from dried Cordyceps sinensis (Berk.) Sacc., a Chinese traditional medicine, was tested for antitumor activity in vivo and in vitro. Ehrlich ascites carcinoma cells (EAC), allogeneic to ICR mice and Meth A fibrosarcoma (Meth A), syngeneic to BALB/c mice were used as the target tumor cell lines. Mice were inoculated i.p. with 1 x 10(6) EAC or 1 x 10(5) Meth A on Day 0, and ECS or saline (control) was injected i.p. to the mice from Day 1 to Day 4. ECS-treatment increased the median survival time of the allogeneic mice inoculated with EAC to 316% of the control. Eight of the 10 ECS-treated mice survived on the 60th day (Day 60) after EAC implantation. ECS-treatment also increased the median survival time of the syngeneic mice inoculated with Meth A to 312% of the control. Half of the ECS-treated mice survived on Day 60. On the other hand, no cytotoxic effect of ECS was found on either EAC or Meth A in vitro. The antitumor effect of ECS seen in the allogeneic mice was significantly reduced when the mice received whole body X- irradiation (5 Gy) before EAC implantation. These results suggest that the antitumor effect of ECS may be mediated through its immunomodulating action.
   

  Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism. World J Gastroenterol. Mar2003;9(3):529-33.:

 AIM: To investigate the inhibitive effect and its possible mechanism of Cordyceps Sinensis (CS) on CCl(4)-plus ethanol-induced hepatic fibrogenesis in experimental rats. METHODS: Rats were randomly allocated into a normal control group, a model control group and a CS group. The latter two groups were administered with CCl(4) and ethanol solution at the beginning of the experiment to induce hepatic fibrosis. The CS group was also treated with CS 10 days after the beginning of CCl(4) and ethanol administration. All control groups were given corresponding placebo at the same time. At the end of the 9th week, rats in each group were humanely sacrificed. Blood and tissue specimens were taken. Biochemical, radioimmunological, immunohistochemical and molecular biological examinations were used to determine the level change of ALT, AST, HA, LN content in serum and TGFbeta(1), PDGF, collagen I and III expression in tissue at either protein or mRNA level or both of them. RESULTS: As compared with the model control group, serum ALT, AST, HA, and LN content levels were markedly dropped in CS group (86.0+/-34.4 vs 224.3+/-178.9, 146.7+/-60.2 vs 272.6+/-130.1, 202.0+/-79.3 vs 316.5+/-94.1 and 50.4+/-3.0 vs 59.7+/-9.8, respectively, P<0.05). Tissue expression of TGFbeta(1) and its mRNA, collagen I mRNA were also markedly decreased (0.2+/-0.14 vs 1.73+/-1.40, 1.68+/-0.47 vs 3.17+/-1.17, 1.10+/-0.84 vs 2.64+/-1.40, respectively, P<0.05). More dramatical drop could be seen in PDGF expression (0.87+/-0.43 vs 1.91+/-0.74, P<0.01). Although there was no statistical significance, it was still strongly suggested that collagen III mRNA expression was also decreased in CS group as compared with model control group (0.36+/-0.27 vs 0.95+/-0.65, P=0.0615). In this experiment, no significant change could be found in PDGF mRNA expression between two groups (0.35+/-0.34 vs0.70+/-0.46, P>0.05). CONCLUSION: Cordyceps sinensis could inhibit hepatic fibrogenesis derived from chronic liver injury, retard the development of cirrhosis, and notably ameliorate the liver function. Its possible mechanism involves inhibiting TGFbeta(1) expression, and thereby, down regulating PDGF expression, preventing HSC activation and deposition of procollagen I and III.

  Immunosuppressive Effect of Cultured Cordyceps sinensis on Cellular Immune Response. Chung Hsi I Chieh Ho Tsa Chih. Aug1990;10(8):485-7, 454.:

 The immunosuppressive effect of cultured Cordyceps sinensis (Bei Lin Capsule) was studied in vitro and in vivo. When the drug was added from 0.6 mg/ml to 5 mg/ml a significant dose-dependent inhibition effect was shown in the following immune reactions of mice (P less than 0.05-0.01): phagocytic function of peripheral blood leucocytes assayed by chemiluminescence; mitogenic response of spleen lymphocytes to Con A; mixed lymphocyte culture and LPS induced interleukin-1 release of macrophages. The survival rate of mice spleen lymphocytes cultured with Cordyceps sinensis 5 mg/ml in 37 degrees C 5% CO2 for 5 days was more than 80%. Cordyceps sinensis 4 g/kg daily significantly prolonged the mice skin allograft survival time (12.7 +/- 2.2 days v.s. 8.3 +/- 0.7 days in the control, P less than 0.01) and its immunosuppressive effect was close to that of Cyclosporin A 5 mg/kg daily on skin allograft.


  Influence of Cordyceps sinensis (Berk.) Sacc. and Rat Serum Containing Same Medicine on IL-1, IFN and TNF Produced by Rat Kupffer Cells. Chung Kuo Chung Yao Tsa Chih. Jun1996;21(6):367-9, 384..:

 The results indicated that the levels of IL-1, IFN, and TNF, especially those of IL-1 and INF, produced by cultured rat kupffer cells were increased in the presence of Cordyceps sinensis (CS) or the drug serum (DS) from rats fed on CS. The experimental result of DS was similar to that of CS. However, the former had a better repeat ability and stability.

  Cordyceps sinensis As An Immunomodulatory Agent. Am J Chin Med. 1996;24(2):111-25.:

 Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the lymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF- alpha) production on human mononuclear cells (HMNC) were studied. Two of the 15 column fractions (CS-36-39 and CS-48-51) significantly inhibited the blastogenesis response (IC50 = 71.0 +/- 3.0 and 21.7 +/- 2.0 micrograms/ml, respectively), NK cell activity (IC50 = 25.0 +/- 2.5 and 12.9 +/- 5.8 micrograms/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC50 = 9.6 +/- 2.3 and 5.5 +/- 1.6 micrograms/ml, respectively). TNF-alpha production in HMNC cultures was also blocked by CS-36 39 and CS-48-51 (IC50 = 2.7 +/- 1.0 and 12.5 +/- 3.8 micrograms/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.

  Augmentation of Various Immune Reactivities of Tumor-bearing Hosts With An Extract of Cordyceps sinensis. Biotherapy. 1990;2(3):199-205.:

 In order to enhance general reactivity of immune system in the tumor- bearing host, we employed extract of Cordyceps sinensis (CSE) as a biological response modifier. Cordyceps sinensis is an interesting material produced by a kind of mushroom parasitic to larval moths and was used to hasten recovery from exhaustion in ancient China. In this experiment, C57BL/6 mice implanted subcutaneously with syngeneic EL-4 lymphoma cells were employed as the host. Oral administration of the extract leads to a reduction of tumor size and prolongation of the host survival time. As judged by plaque-forming cells against T- dependent (sheep erythrocytes) and T-independent (bacterial lipopolysaccharide) antigens, CSE showed to augment the antibody responses. As for the activities of peritoneal macrophages, chemotaxis was dramatically depressed within a few days after EL-4 transplantation up to the end of life, but treatment with CSE at -14, -7, -4, +4, +7 and +10 days after the tumor transplantation augmented the activity about four times stronger than that of control. Phagocytic activity of macrophages was also decreased in tumor- bearing mice treated with cyclophosphamide (100 mg/kg) 3 and 5 days after tumor transplantation. But administration of CSE restored the activity to more than the normal level. The overall efficacy of CSE was tested with protective activity against systemic infection by Salmonella enteritides. The tumor-bearing mice receiving this medicine lived significantly longer than any other groups without CSE.

  The Scientific Rediscovery of a Precious Ancient Chinese Herbal Regimen: Cordyceps sinensis: Part II. J Altern Complement Med. 1998;4(4):429-57.:

 Cordyceps sinensis (Berk.) Sacc. is a time-honored tonic food and herbal medicine in China, where recent research has shown that many of its traditional uses may be viewed from the basis of pharmacological activities. The ongoing exploration of C. sinensis in its wild form and cultured, fermented mycelial products derived from it, are reviewed from English and Chinese literature. Part II concludes the series with a review of C. sinensis in preclinical in vitro and in vivo studies, and open-label and double-blinded clinical trials on the respiratory, renal, hepatic, cardiovascular, immunologic, and nervous systems, and its effects on cancer, glucose metabolism, inflammatory conditions, and toxicological studies. In Part I, which appeared in the Fall 1998 issue of this journal (4(3):289-303), we discussed the effects of C. sinensis on antisenescence, endocrine and sexual functions, atherosclerosis, hyperlipidemia, and free radicals.

  Amelioration of Aminoglycoside Nephrotoxicity by Cordyceps sinensis in Old Patients. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. May1994;14(5):271-73.:

 The protective effect on aminoglycoside nephrotoxicity by Cordyceps sinensis in the old patient was observed. 21 old patients were randomly divided into two groups. Each group received amikacin sulfate for 6 days. In addition, group A was administered Cordyceps sinensis for 7 days and group B was given placebo. The results revealed that group A developed less prominent nephrotoxicity compared with group B as evidenced by less urinary nephro- aminoglycosidase (NAGase) and beta-microglobulin in group A than those in Group B. These results suggested that Cordyceps sinensis exerted a protective effect on aminoglycoside nephrotoxicity in the old patients.
 


  Cordyceps sinensis in Protection of the Kidney from Cyclosporine A Nephrotoxicity. Chung Hua I Hsueh Tsa Chih. Jul1993;73(7):410-12.:

 To explore the protective effect of cordyceps sinensis (CS) on cyclosporine A nephro-toxicity (CsA-Nx) and the possible mechanism, we studied the kidney changes induced by CsA in rats by light microscopy (LM), electronic microscopy (EM) and morphometrical analysis. At the 15th day after receiving CsA, prominent vacuolation and necrosis were noted microscopically in proximal tubular cells and mitochondria swelling electronmicroscopically. Morphometrical study showed that the epithelial areas of both proximal and distal tubules in the CS group were larger than those of the control group. There were obvious vacuolation (90%) and necrosis in proximal tubular cells at different stages of chronic CsA-Nx. Interstitial edema with mild fibrosis was observed. Mitochondria abnormality was seen electronmicroscopically. Morphometrical analysis showed that the epithelial cell areas of tubules and glomeruli were smaller in the CsA group than those in the CS group. Both acute and chronic experiments showed that CS could protect the kidney from CsA-Nx and ameliorate the glomerular and interstitial injuries.

  Mechanisms and Therapeutic Effect of Cordyceps sinensis (CS) on Aminoglycoside Induced Acute Renal Failure (ARF) in Rats. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. May1992;12(5):288-91.:

 Nephrotoxic ARF model of rat was induced by IP injection of either Gentamycin or Kanamycin and treated with CS. The results of study showed that the simultaneous administration of CS with Gentamycin could protect the proximal tubular cells from Gentamycin toxicity and the use of CS after the establishment of Kanamycin nephrotoxic ARF could prompt an earlier recovery from ARF as compared with the control group. The possible mechanisms of CS on ARF include: (1) protecting tubular cell sodium pump activity; (2) attenuating tubular cell lysosome overfunction stimulated by phagocytosis of aminoglycoside; (3) decreasing tubular cell lipoperoxidation in response to toxic injury.

  Anti-oxidation of Paecilomyces sinensis. Chung Kuo Chung Yao Tsa Chih. Apr1991;16(4): 240-42.:

 This paper indicates that Paecilomyces sinensis ig 3g/kg/dx14 increases the amount of superoxide dismutase in the liver tissues of mice; that Paecilomyces sinensis is similar to natural Cordyceps sinensis in inhibiting the production of Lpo and increasing the amount of superoxide dismutase in the liver homogenates of mice in vitro. In addition Paecilomyces sinensis can also increase the amount of glutathione peroxidase in the liver homogenates of mice in vitro.

  Cordyceps sinensis extracts do not prevent Fas-receptor and hydrogen peroxide-induced T-cell apoptosis.:

 Aqueous and alcohol extracts of Cordyceps sinensis (Berk) Succ. are used as a traditional medicine in China for the treatment of a wide range of diseases and are reported to have antioxidant and antiapoptotic properties. We therefore examined the ability of aqueous, organic, and alcohol extracts of Cordyceps sinensis to inhibit apoptosis induced either by hydrogen peroxide or Fas-receptor ligation; both stimuli induce apoptosis dependent on reactive oxygen species. Cells pre-incubated with Cordyceps sinensis extracts were equally sensitive to hydrogen peroxide and Fas-mediated apoptosis. Thus, the putative antioxidant and antiapoptotic properties of Cordyceps sinensis are insufficient to rescue cells from apoptosis induced by these stimuli in vitro.
 


  Effects of a commercial herbal-based formula on exercise performance in cyclists.:

 INTRODUCTION/PURPOSE: We examined the effects of a commercially marketed herbal-based formula purported to increase endurance on oxygen consumption (VO2) in 17 competitive category III/IV amateur cyclists [mean (SEM) age: 31.1 (1.8) yr; height: 178.5 (1.8) cm; weight: 77.1 (1.6) kg]. METHODS: Each cyclist participated in two (pre/post) cycling tests progressing 25 W.4 min(-1) starting at 100 W administered in a randomized, placebo-controlled, double-blind fashion. The second trial was performed 14 d after the ingestion of a manufacturer recommended loading phase (4 d x 6 caps.d(-1)) and a maintenance phase (11 d x 3 caps.d(-1)). Three treatment capsules contained 1000 mg of Cordyceps sinensis (CS-4) and 300 mg Rhodiola rosea root extract as the primary ingredients; 800 mg of other ingredients included calcium pyruvate, sodium phosphate, potassium phosphate, ribose, and adenosine and 200 mcg of chromium. RESULTS: Using a 2 x 2 ANOVA, we observed no significant treatment effect for any between or within group variables including peak VO2 [treatment 4.14 (0.2) L.min(-1); placebo 4.10 (0.2) L.min(-1)], time to exhaustion [treatment 38.47 (1.7) min; placebo 36.95 (1.8) min], peak power output (PO) [treatment 300.00 (12.1) W; placebo 290.63 (12.9) W], or peak heart rate. We also observed no differences for any subpeak exercise variable including the PO eliciting 2 mmol.L(-1) blood lactate (BLa) [treatment 201.00 (18.1) W; placebo 167.50 (19.2) W] and 4 mmol.L(-1) BLa [treatment 235.88 (15.8) W; placebo 244.78 (14.9) W], ventilatory threshold, respiratory compensation point, or Vo2 L.min(-1) gross efficiency at each stage. CONCLUSION: A 2-wk ingestion schema of a commercial herbal-based formula is insufficient to elicit positive changes in cycling performance.

  Nucleoside from Cordyceps kyushuensis and the distribution of two active components in its different parts.:

 AIM: To rapidly separate and determine the nucleosides from natural and cultured Cordyceps kyushuensis Kob., and to compare the content of cordycepin and adenosine in different parts of Cordyceps kyushuensis Kob., which are the main nucleoside active components in medicinal fungus belonging to Cordyceps (Fr.) Link. METHODS: The nucleosides were separated and determined by the high performance capillary zone electrophoresis (CZE). Beckman P/ACE system MDQ apparatus equipped with a PDA detector and a uncoated fused-silica capillary (41 cm x 45 microns ID, 30 cm effective length) were used. The experimental conditions were as follows: the running buffer was borax solution (adjust to pH 9.4 with sodium hydroxide), applied voltage was 20 kV, operated temperature was 20 degrees C and the detector wavelength was 258 nm. The content of cordycepin and adenosine in the fruiting body, stroma and host worm of natural and cultured C. kyushuensis were respectively investigated and quantitatively analyzed. RESULTS: There are at least 8 kinds of nucleoside or nitrogen base in Cordyceps kyushuensis Kob. The content of cordycepin which is a bio-active substance with anti-tumor activity in C. kyushuensis is significantly higher than that in C. sinensis and C. militaris, and furthermore the cordycepin in the cultured C. kyushuensis is notably higher than the natural one. Adenosine was mainly found from the stroma of C. kyushuensis, While the cordycepin content is high in the stroma of both natural and cultured C. kyushuensis as well as in the host worm of the cultured one. CONCLUSION: There are some differences about the nucleoside components between the natural and cultured C. kyushuensis and between the different parts of them. With a high cordycepin content, C. kyushuensis should have a considerable medicinal potential.


  Scientific References:

  1.Cordyceps sinensis:The longevity and energy mushroom with history application for more than 3,000 years......
  2.Research Update of Cordyceps sinensis and Its findings......