Phytochemistry 1999 Aug; 51(7):891-8
Antitumor sterols from the mycelia of Cordyceps sinensis.
Bok JW, Lermer L, Chilton J, Klingeman HG, Towers GH, Department of Botany, University of British Columbia, Vancouver, Canada.
Activity guided fractionations led to the isolation of two antitumor compounds 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-dien-3 beta-D-glucopyranoside and 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3 beta-ol from the methanol extract of Cordyceps sinensis. Two previously known compounds, ergosteryl-3-O-beta-D-glucopyranoside and 22-dihydroergosteryl-3-O-beta-D-glucopyranoside were also isolated. The structures of hitherto unknown sterols were established by 1D and 2D NMR spectroscopic techniques with the former synthesized in order to confirm the identity of the sugar moiety by chemical correlation. The glycosylated form of ergosterol peroxide was found to be a greater inhibitor to the proliferation of K562, Jurkat, WM-1341, HL-60 and RPMI-8226 tumor cell lines by 10 to 40% at 10 micrograms/ml than its previously identified aglycone, 5 alpha,8 alpha-epidioxy-24(R)-methylcholesta-6,22-dien-3 beta-ol. PMID: 10423860, UI: 99352659
J Lab Clin Med 1999 Jan; 133(1):55-63
Inhibition of activated human mesangial cell proliferation by the natural product of Cordyceps sinensis (H1-A): an implication for treatment of IgA mesangial nephropathy.
Lin CY, Ku FM, Kuo YC, Chen CF, Chen WP, Chen A, Shiao MS, Department of Pediatrics and Medical Research, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Cordyceps sinensis (CS) is a parasitic fungus that has been used as a Chinese medicine for a long time in the treatment of nephritis. Today, the hypothesis about the pathogenesis of immunoglobulin A nephropathy (IgAN) is that nephritogenic IgA immune complexes (IgAIC) go to the kidney to stimulate resting mesangial cells to release cytokines and growth factors. These cytokines and growth factors cause mesangial cell proliferation and release matrix, chemical mediators that lead to the glomerular injury. However, nephritogenic IgAIC in humans is still unknown. To solve this problem previously, we established an in vitro model that showed that cultured human mesangial cells (HMC) stimulated with interleukin-1 (IL-1) plus IL-6 can cause mesangial cell proliferation, increasing production of chemical mediators and superoxide anion. An in vivo model also proved that this culture medium may lead to renal injury with hematuria and proteinuria. Therefore, to fractionate the crude components that can be used in the treatment of patients with IgAN, we cultured HMC, and then an HMC activating model with HMC incubated with IL-1 and IL-6 was established. We fractionated the crude methanolic extracts from fruiting bodies of CS with the use of this in vitro inhibition of HMC activation model as our assay method. In brief, the fruiting bodies were extracted by silica gel column chromatography. One out of 6 column fractions, F-2, significantly inhibited the HMC activation by IL-1 plus IL-6. The acute toxicity test with male Institute of Cancer Research mice showed no liver toxicity or mutagenicity. Then we established an IgAN animal model with R36A (Pneumococcal C-polysaccharide purified from Streptococcus pneumoniae) as antigen and anti-R36A IgA monoclonal antibody to form nephritogenic IgA-IC, which can induce hematuria and proteinuria in mice with IgA deposition in the mesangial area. The mice in the IgAN model fed with 1% F-2 in diet had significant reduction of hematuria and proteinuria together with histopathologic improvement. Therefore this fraction was then purified by silica gel column chromatography and high-performance liquid chromatography, which got a purified compound H1-A, which can suppress the activated HMC and alleviate IgAN (Berger's disease) with clinical and histologic improvement. These results give us a new regimen for the treatment of patients with IgAN in the future. PMID: 10385482, UI: 99312208
Jpn J Pharmacol 1999 Apr; 79(4):505-8
Activation of in vivo Kupffer cell function by oral administration of Cordyceps sinensis in rats.
Nakamura K, Yamaguchi Y, Kagota S, Shinozuka K, Kunitomo M, Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
We investigated the effect of water extracts of Cordyceps sinensis (WECS) on Kupffer cell function in rats. Rats were received a single i.v. injection of a colloidal carbon solution and then the clearance rate from the blood were measured. The rats had been daily administered with WECS, p.o. at a dose of 200 mg/kg for 25 days until the day before the injection of colloidal carbon. The half-life of the colloidal carbon in the blood of rats administered WECS 200 mg/kg was significantly shorter than that of the control rats. This suggests that accelerated function of Kupffer cells is partially involved in the anti-metastatic action of WECS. PMID: 10361894, UI: 99288740
Jpn J Pharmacol 1999 Mar; 79(3):335-41
Inhibitory effect of Cordyceps sinensis on spontaneous liver metastasis of Lewis lung carcinoma and B16 melanoma cells in syngeneic mice.
Nakamura K, Yamaguchi Y, Kagota S, Kwon YM, Shinozuka K, Kunitomo M, Department of Pharmacology, Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
We investigated the effect of the water extract of Cordyceps sinensis (WECS) on liver metastasis of Lewis lung carcinoma (LLC) and B16 melanoma (B16) cells in mice. C57BL/6 mice were given a s.c. injection of LLC and B16 cells and sacrificed 20 and 26 days after tumor inoculation, respectively. WECS was daily administered p.o. to the mice in a dose of 100 mg/kg body weight (wt.) in the experiment of LLC and in a dose of 100 or 200 mg/kg body wt. in the experiment of B16 from one week before tumor inoculation to one day before the date of sacrifice. The tumor cells increased in the thigh in LLC-inoculated mice and in the footpad in B16-inoculated mice. The relative liver wt. of the tumor-inoculated mice significantly increased as compared to that of the normal mice due to the tumor metastasis, as verified by the hematoxylin-eosin staining pathological study in the LLC experiment. The relative liver wt. of the WECS-administered mice significantly decreased relative to that of the control mice in both the LLC and B16 experiments. WECS showed a strong cytotoxicity against LLC and B16 cells, while cordycepin (3'-deoxyadenosine), an active component of WECS, was not cytotoxic against these cells. These findings suggest that WECS has an anti-metastatic activity that is probably due to components other than cordycepin. PMID: 10230862, UI: 99245893
J Altern Complement Med 1998 Fall; 4(3):289-303
The scientific rediscovery of an ancient Chinese herbal medicine: Cordyceps sinensis: part I.
Zhu JS, Halpern GM, Jones K, Department of Pediatrics, Stanford University School of Medicine, California, USA.
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.
Publication Types: Review, tutorial, PMID: 9884180, UI: 99098649
J Altern Complement Med 1998 Winter; 4(4):429-57
The scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis: part II.
Zhu JS, Halpern GM, Jones K, Department of Pediatrics, Stanford University School of Medicine, California, USA.
This review presents Cordyceps sinensis (Berk.) Sacc., a fungus highly valued in China as a tonic food and herbal medicine. The extant records show the continued use of C. sinensis is now centuries old. The major chemical, pharmacological, and toxicological studies on C. sinensis and the various derived, cultured, fermented mycelial products currently in use are reviewed from the English and Chinese literature. Preclinical in vitro and in vivo studies and clinical blinded or open-label trials in to date over 2000 patients are reviewed. These studies show the main activities of the fungus in oxygen-free radical scavenging, antisenescence, endocrine, hypolipidemic, antiatherosclerotic, and sexual function-restorative activities. The safety of the fungus, its effects on the nervous system, glucose metabolism, the respiratory, hepatic, cardiovascular, and immune systems, immunologic disease, inflammatory conditions, cancer, and diseases of the kidney will be reviewed in the second part of this article to be published in the winter issue of this journal. PMID: 9764768, UI: 98435797
Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1997 Jan; 17(1):35-8
[Clinical and experimental studies on elimination of oxygen free radical of jinshuibao capsule in treating senile deficiency syndrome and its deoxyribonucleic acid damage repairing effects].
[Article in Chinese] Zhang ZJ, Luo HL, Li JS, Second Affiliated Hospital of Jiangxi Medical College, Nanchang.
OBJECTIVE: To observe the efficacy of Jinshuibao capsule. METHODS: Senile patients of Deficiency Syndrome treated with Jinshuibao capsule (JSBC) as treated group and with starch capsule as control group. JSBC is a preparation of Cordyceps sinensis. RESULTS: (1) The superoxide dismutase (SOD) activity in senile patient were markedly lower than that in youth, while the malonyldialdehyde (MDA) level of the former was higher than that of the latter, P < 0.01; (2) The SOD activity increased and the MDA level decreased in the treated group after treatment, P < 0.01. JSBC also revealed satisfactory effect on relieving symptoms such as chilling, dizziness, lassitude in loin and legs, frequent nocturia and tinnitus, etc. Results of animal experiment wese in accordance with that of clinical observation. The unscheduled deoxyribonucleic synthesis (UDS) level of aged group before treatment was obviously lower than that of youth; after treatment, the change was very significant, and the difference between treated group and control group was also very significant (P < 0.01). Animal experiment showed that the sister chromatid exchange (SCE) of splenic cell in young mice group was markedly lower than that in aged mouse group. CONCLUSION: JSBC has not showed the SCE inducting effect, but could accelerate the repairing of damaged deoxyribonucleic acid (DNA). PMID: 9812650, UI: 99029193
Am J Chin Med 1998; 26(2):159-70
Cordyceps sinensis increases the expression of major histocompatibility complex class II antigens on human hepatoma cell line HA22T/VGH cells.
Chiu JH, Ju CH, Wu LH, Lui WY, Wu CW, Shiao MS, Hong CY, Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Previous studies suggest that down-regulation of the major histocompatibility complex (MHC) antigens on the cell surface of certain tumors results in an escape of immune surveillance. Cordyceps sinensis is well known for its modulatory effect on host immune system. To investigate the modulatory effect of Cordyceps sinensis on MHC class II antigen expression on hepatoma cells, immunostaining with monoclonal antibody (MAb) L243, against the HLA DR region of MHC class II antigens on human hepatoma cell line HA22T/VGH was analyzed by using flow cytofluorimetry. The degree of fluorescence intensity on L243(+) cells was expressed as relative mean fluorescence intensity (RMFI). The extract of Cordyceps sinensis (VGH-CS-ME-82, 40 micrograms/ml) was found to increase the MHC class II antigen expression on HA22T/VGH cells with the percentage of L243(+) cells 40.2 +/- 2.5 and RMFI 6.6 +/- 0.4; whereas cells without treatment disclosed the percentage of L243(+) cells 17.2 +/- 1.4 and RMFI 5.4 +/- 0.3, respectively (p < 0.05). There was a dose-related increase in the degree of fluorescence intensity in terms of RMFI on VGH-CS-ME-82 induced cells. The RMFI in cells treated with IFN-gamma 0, 0.2 and 5 ng/ml were 5.4 +/- 0.3, 8.2 +/- 0.4, and 24.9 +/- 1.5, respectively; whereas the RMFI in cells co-incubated with VGH-CS-ME-82 (40 micrograms/ml) and IFN-gamma 0, 0.2 ng/ml and 5 ng/ml were 6.7 +/- 0.2 (p < 0.05), 9.2 +/- 0.9 (p < 0.1) and 29.5 +/- 1.2 (p < 0.005), respectively. We conclude that VGH-CS-ME-82, either alone or with IFN-gamma induction, increases the MHC class II antigen expression on hepatoma cell line HA22T/VGH, which will shed light into the present immunotherapy, and make the host immune surveillance more effective against tumor cells with down-regulated MHC class II antigen expression. PMID: 9799968, UI: 99016350
Chung Kuo Chung Hsi I Chieh Ho Tsa Chih 1996 Dec; 16(12):733-7
[Experimental study on effect of Cordyceps sinensis in ameliorating aminoglycoside induced nephrotoxicity].
[Article in Chinese]
Li LS, Zheng F, Liu ZH, Research Institute of Nephrology, Jinling Hospital, Nanjing.
In order to evaluate the effect of Cordyceps sinensis (CS) on aminoglycoside (AG) induced nephrotoxicity, gentamycin was imposed on the young and old rats with CS administration. The renal tubular injury was ameliorated as evidenced by less prominent increment of BUN, SCr, sodium excretion, urinary NAGase and less severity of histopathological changes as compared with control. In addition, the use of CS could promote an earlier recovery of renal oxygen consumption insulin clearance, and sodium absorption in isolated perfused kidney from CS treated intoxicated rat than that from control. Possible mechanisms of CS on drug-induced nephrotoxicity include: (1) Accelerating the regeneration of tubular cells; (2) Protecting the sodium pump activity of tubular cells; (3) Attenuating the tubular cell lysosome hyperfunction stimulated by phagocytosis of AG as well as decreasing the tubular cell lipoperoxidation in response to toxic injury; (4) Reducing the tissue Ca++ content. PMID: 9772591, UI: 98445768
J Cell Biochem 1998 Jun 15; 69(4):483-9
Effects of a water-soluble extract of Cordyceps sinensis on steroidogenesis and capsular morphology of lipid droplets in cultured rat adrenocortical cells.
Wang SM, Lee LJ, Lin WW, Chang CM, Department of Anatomy, College of Medicine, National Taiwan University, Taipei, Republic of China.
Journal of Food and Drug Analysis, Vol. 8, No. 4, 2000, Pages
Pharmacological Functions of Chinese Medicinal Fungus Cordyceps sinensis and Related Species
SHENG-YUAN WANG1, 2 AND MING-SHI SHIAO1*
1. Department of Medical Research and Education, Veterans General Hospital-Taipei, 201, Shih-Pai Rd., Section 2, Taipei, Taiwan 112, R.O.C.
2. Institute of Traditional Medicine, National Yang-Ming University, 155, Li Nung St., Section 2, Taipei, Taiwan 112, R.O.C.
Cordyceps sinensis, an entomogenous fungus used in traditional Chinese medicine, exhibits very broad biological and pharmacological actions in hepatic, renal, cardiovascular, and immunologic systems as well as anticancer activity. Pharmacological functions of Cordyceps are primarily due to the bioactive polysaccharides, modified nucleosides, and cyclosporin-like metabolites produced by this fungus and related species. The beneficial effects on renal and hepatic function and immunomodulation-related antitumor activities are most promising and deserve great attention. Many previous studies used fruiting bodies, but recently an increasing number of studies have used cultured mycelia in investigations. It is difficult to determine if the same bioactive ingredients exist in fruiting bodies and cultured mycelia and contribute to the pharmacological actions reported in the literature. More mechanism-based, disease-oriented pharmacological studies are required to ensure clinical efficacy for particular diseases. Adjuvant therapy using C. sinensis for immune function disturbances, cancer, and renal failure is possible if double-blind, randomized placebo-control clinical studies show the efficacy of this herb.
Key words: Cordyceps sinensis, anticancer activities, hepatic function, renal function, immunomodulation, polysaccharides, modified nucleosides