| Compound | Source | Bioactivity Nucleosides | Dosage | Effect | References |
|---|---|---|---|---|---|
| Nucleosides | |||||
| Cordycepin | Cultured C. militaris | Anticancer | 15 mg/kg/day (2 weeks), p.o. | Inhibited B16 tumor lump in mice | Yoshikawa et al. 2004 |
| 100 μM (48 hours) | Inhibited the proliferation of B16 and HepG2 cells | Wu, Zhang, and Leung 2007a | |||
| 0.3, 1, 3 mg/mL | Antimetastatic action in a hematogenic lung metastatic mouse model in vivo and a chemoinvasion chamber model on B16 cells in vitro | Nakamura et al. 2005 | |||
| 100 μM | Induced cell apoptosis in OEC-M1 human oral squamous cancer cells; human hepatocellular carcinoma BEL-7402 cells; MA-10 mouse Leydig tumor cells | Wu et al. 2007b; Shi et al. 2008; Jen et al. 2009 | |||
| 10 μM | Resulted in cell death in multiple myeloma cells | Chen, Stellrecht, and Gandhi 2008 | |||
| 67 μM | Modulated polyadenylate polymerase in HeLa and MCF-7 cells via cell cycle rather than apoptosis induction | Thomadaki, Tsiapalis, and Scorilas 2005 | |||
| 20 μg/mL | Modulated polyadenylate polymerase in human T cells, acute lymphoblastic leukemia, and human Burkitt lymphoma cells | Thomadaki, Tsiapalis, and Scorilas 2008 | |||
| Antirestenosis | 20 μM/day (21 days), i.p. | Inhibited neointima formation in balloon injury in rats, and 40% and 50% decrease in proliferation and migration of rat aortic vascular smooth muscle cells in vitro | Chang et al. 2008b | ||
| Immunomodulatory activity | 0.75–240.0 μg/mL | Induced the production of IL-1β, IL-6, IL-10, and TNF-α from resting HPBMC and the proliferation of CD4+, CD8+, CD19+, CD56+, and CD 14+ cells; suppressed PHA-induced secretion of IL-2, IL-4, IL-5, IFN-γ, and IL-12 from HPBMC and reduced the proliferation of these cells | Zhou et al. 2002 and 2008 | ||
| 5–30 μg/mL | Inhibited NO release from LPS-stimulated macrophages by downregulation of iNOS, COX-2 expression, and TNF-α through the suppression of NF-αB activation, Akt, and p38 phosphorylation | Kim et al. 2006b | |||
| 10–100 μM | Was a potent inhibitor of IL-1β-induced epithelial neutrophil-activating peptide and MMP-1 and 3 and strongly blocked the p38/JNK/AP-1 signaling pathway in rheumatoid arthritis synobial fibroblasts | Noh et al. 2009 | |||
| Antioxidant activity | 10 mg/kg (10 days) | Reduced neuronal damage and gial activation via downregulation of lipid peroxidation in the ischemic CA1 region and decrease in activation of astrocytes and microglia | Hwang et al. 2008 | ||
| Antibacterial | 10 μg/disk | Revealed potent growth-inhibiting activity toward Clostridium paraputrificum and Clostridium perfringens | Ahn et al. 2000 | ||
| Antithrombotic activity | 10–500 μ | Inhibited 1 μM thapsigargin-induced, 5 μM U46619-induced, and 10 μg/mL collagen-induced platelet aggregation through [Ca2+]i-regulating system | Cho et al. 2006, 2007a,b | ||
| Human African trypanosomiasis | 0.1–100.0 μM (48-hours) | Reduced the growth of Trypanosoma brucei and T. cruzi, as well as Leishmania major and L. amazonensis | Rottenberg et al. 2005 | ||
| 1 or 2 mg/kg (4 or 7 days) | Administration of cordycepin plus deoxycofomycin to T. cruzi-infected mice significantly reduced parasitemia | ||||
| Insecticidal activity | 25–500 mg/L (2–5 days) | Larvicidal activity against Plutella xylostella | Kim et al. 2002 | ||
| Guanosine | Cultured C. sinensis | 0.02 and 0.10 μM | Decreased NO release, but augmented TNF-α and IL-1β release from primary rat macrophages | Yu et al. 2007 | |
| Adenosine | Cultured C. sinensis | 0.30 and 1.50 μM | Decreased NO release, but augmented IL-1β release from primary rat macrophages | Yu et al. 2007 | |
| Ergosterol | Cultivated mycelium of C. sinensis | Anticancer activity | 100 μM (48 hours) | Showed cytotoxicity on MCF-7, B16, HL-60, and HepG2 in vitro | Wu, Zhang, and Leung 2007a |
| 10–40 μg/mL | Exhibited cytotoxicity activity on HL-60 cells with IC50 values of 23.3 μg/mL | Matsuda et al. 2009 | |||
| Sterols | |||||
| β-Sitosterol | Anticancer activity | 100 μM (48 hours) | Showed more potential cytotoxic effect than ergosterol on MCF-7, B16, HL-60, and HepG2 in vitro | Wu, Zhang, and Leung 2007a | |
| 10–80 μg/mL | Exhibited cytotoxicity activity on HL-60 cells with IC50 values of 26.7 and 23.3 μg/mL | Matsuda et al. 2009 | |||
| 5α,8α-Epidioxy-24(R)-methylcholesta-6,22-dien-3β-D-glucopyranoside | C. sinensis methanol extract | Anticancer activity | 10–200 μM (22 hours) | Showed significant inhibitory effects on K562, Jurkat, HL-60, WM1341, and RPMI 8226 cells | Bok et al. 1999 |
| 5α,8α-Epidioxy-24(R)-methylcholesta-6,22-dien-3β-ol | C. sinensis methanol extract | Anticancer activity | 10–200 μM (22 hours) | Showed significant inhibitory effects on K562, Jurkat, HL-60, WM1341, and RPMI 8226 cells | Bok et al. 1999 |
| 5α,8α-Epidioxy-22E-ergosta-6,22-dien-3β-ol | Cultivated C. sinensis mycelium | Anticancer activity | 1.9–10.0 μg/mL | Showed substantial cytotoxic activity on HL-60 cells with IC50 values of 7.8 μg/mL, and the apoptosis was related with the activation of caspases-3/7 | Matsuda et al. 2009 |
| 5α,8α-Epidioxy-22E-ergosta-6,9(11),22-trien-3β-ol | Cultivated C. sinensis mycelium | Anticancer activity | 1.9–10.0 μg/mL | Showed substantial cytotoxic activity on HL-60 cells with IC50 values of 7.5 μg/mL, and the apoptosis was related with the activation of caspases-3/7 | Matsuda et al. 2009 |
| 5α,6α-Epoxy-5α-ergosta-7,22-dien-3β-ol | Cultivated C. sinensis mycelium | Anticancer activity | 1.9–10.0 μg/mL | Showed substantial cytotoxic activity on HL-60 cells with IC50 values of 7.3 μg/mL, and the apoptosis was related with the activation of caspases-3/7 | Matsuda et al. 2009 |
| Ergosterol peroxide (C28H44O3; Cpd 6A) | Natural C. cicadae MeOH extract | Immunomodulatory activity | 1.5–100 μM | Reversed PHA-induced increase of cyclin E, IL-2, IL-4, IL-10, and IFN-γ in primary human T cells | Kuo et al. 2003 |
| H1-A | Natural C. sinensis | Treatment of kidney | 40 μg/kg/day, p.o. (8 weeks) | Demonstrated significantly less proteinuria, lower serum creatinine level, and less renal mesangial proliferation in MRL lpr/lpr mice | Yang et al. 1999 |
| 40 mM | Inhibited the proliferation of human mesangial cells stimulated by IL-1 plus IL-6 in vitro | Lin et al. 1999 | |||
| 12.5 or 25 mM | Inhibited the cell proliferation and promoted the apoptosis of IL-1- and PDGF-BB-activated human renal mesangial cells | Yang et al. 2003 | |||
| 4γ-acetoxy-scirpendiol | Fruiting bodies of C. takaomantana | Hypoglycemic activity | 0.2–2 mM | Inhibited glucose uptake in HEK193 cells expressing recombinant Na+/GLUT-1 | Yoo and Lee 2006 |
| Polysaccharides | |||||
| Exopolysaccharide fraction | Cultured supernatant of C. sinensis | Anticancer activity | 30–120 mg/kg /2 days (i.p., 28 days) | Inhibited the metastasis of B16 melanoma cells to lungs and livers and Bcl-2 level in the lungs of mice; enhanced the phagocytosis of peritoneal macrophages and proliferation of spleen lymphocytes | Zhang et al. 2005 |
| 15–60 mg/kg (i.p., 7 days) | Inhibited the H22 tumor weight in ICR mice; enhanced the phagocytosis and cytokine release of peritoneal macrophages and proliferation and activity of spleen lymphocytes | Zhang et al. 2008 | |||
| 30–120 mg/kg/2 day (28 days) | Lowered the c-Myc, c-Fos, and VEGF levels in the lungs and livers in B16 tumor-bearing mice | Yang et al. 2005 | |||
| Exopolysaccharide-peptide complexes | Submerged mycelial culture of C. sphecocephala | Anticancer activity | 0.1–1 mg/mL (48 h) | Inhibited the growth of HepG2 and SK-N-SH cells, and the apoptosis of both cancer cells was associated with DNA fragmentation, activation of caspase-3, and modulation of Bcl-2 and Bax | Oh et al. 2008 |
| Mannoglucan | C. sinensis mycelium | Anticancer | N/A | Showed weak cytotoxicity activity against SPC-I cancer cells with IC50 of 63 μg/mL | Wu et al. 2007c |
| CPS-1 (23 kDa) | Aqueous extract of cultured C. militaris | Immunomodulatory activity | 15 mg/kg (i.p.) | Suppressed the humoral immunity; inhibited croton oil-ear edema and acetic acid vascular permeability in mice | Yu et al. 2004 |
| Intracellular polysaccharides (83 kDa) | Mycelia of C. sinensis | Immunomodulatory activity | 100–400 μg/mice on day 1 and 15 (s.c.) | Enhanced the serum IgG, IgG1, and IgG2b levels, but not splenocyte proliferation in ovalbumin-immunized mice | Wu et al. 2006 |
| Polysaccharides | Submerged culture of C. sinensis | Immunomodulatory activity | 0.025–0.1 mg/mL | Polysaccharides from culture filtrate, but not from mycelia, increased the cytokine production of TNF-α, IL-6, and IL-10 from HPBMC, and enhanced the CD11b expression and phagocytosis of HPBMC | Kuo et al. 2007 |
| Polysaccharides | Mycelia of C. gunnii | Immunomodulatory activity | 10, 100 mg/kg | Inhibited mice spleen lymphocytes proliferation, peritoneal macrophage phagocytosis, and cytocoxin T lymphocytes activity | Xiao et al. 2004 |
| Cordysinocan (82 kDa) | UST 2000, a strain of C. sinensis | Immunopotentiating actvity | 0–100 μg/mL | Induced the T lymphocyte proliferation and the secretion of IL-2, IL-6, and IL-8 in vitro; increased the phagocytosis and acid phosphatase activity of macrophages in vitro | Cheung et al. 2009 |
| CS-OHFP | C. sinensis | Hypoglycemic activity | p.o. | Exerted hypoglycemic activity in normal mice | Kiho et al. 1993 |
| Polysaccharide-enriched fraction | Cultured C. militaris | Hypoglycemic activity | 10–40 mg/kg/day(12 days, p.o.) | Showed antihyperglycemic activity in STZ-induced diabetic rats | Zhang et al.2006 |
| CSP-1 (molecular weight about 210 kDa) | Cultured Cordyceps mycelia from Cephalo-sporium sinensis Chen sp. nov. | Hypoglycemic activity | 200 and 400 mg/kg/kg, p.o. | Displayed hypoglycemic effect in normal animals; reduced blood glucose level, but also significantly increased insulin levels in alloxan- and streptozotocin-diabetic mice | Li et al. 2006b |
| Antioxidant activity | 25–100 μg/mL | Reversed the viability, attenuated the GSH-Px and SOD, as well as reduced MDA level in PC12 cells treated with 200 μM H2O2 | Li et al. 2003 | ||
| CS-F30 (45 kDa) | Hot water extract of cultured mycelia of C. sinensis | Hypoglycemic activity | i.p. | Showed antihyperglycemic activity in genetic diabetic mice; lower plasma triglyceride level and cholesterol level | Kiho et al. 1996 |
| i.v. | Exerted hypoglycemic activity in normal and STZ-induced diabetic mice; lower plasma triglyceride level and cholesterol level | ||||
| CS-F10 (15 kDa) | Cultured mycelia of C. sinensis | Hypoglycemic activity | 50 mg/kg, i.p. | Lowered the plasma glucose level in normal, streptozotocin-induced diabetic, and genetic diabetic mice; increased the activities of hepatic glucokinase in STZ-induced mice; decreased protein content of GLUT2 in rat liver | Kiho et al. 1999 |
| CI-P | Caterpillar of C. cidadae | Hypoglycemic activity | N/A | Exerted hypoglycemic activity in normal mice | Kiho et al. 1990 |
| CI-A | Caterpillar of C. cidadae | Hypoglycemic activity | N/A | Exerted hypoglycemic activity in normal mice | Kiho et al. 1990 |
| Polysaccharides | Mycelia of C. sinensis | Antioxidant activity | 100–200 mg/kg | Enhanced SOD activity of liver, brain, and serum as well as GSH-Px activity in liver and brain, reduced MDA level in liver and brain in H22 tumor-bearing mice | Chen et al. 2006 |
| CBP-1 (17 kDa) | Cultured C. militaris | Antioxidant activity | 0–2 mg/mL | Possessed hydroxyl radical–scavenging activity(IC50=0.638 mg/mL) | Yu et al. 2009 |
| Polysaccharides | N/A | Protective effect on kidney | 40–160 mg/kg/day(14 days) | Alleviated freezing-induced chronic renal failure in rats by inhibiting lipid oxidation | Lv et al. 2007 |
| Polysaccharides | Cultured mycelia of C. sinensis | Protective effect on liver fibrosis | 60 mg/kg/day(4 weeks) | Improved the hepatic function (ALT, AST, Alb,and Tbil), SOD, but decreased MDA, Hyp, and IV collagen content, and TMMP-2 level in liver tissue compared with dimethylnitrosamine-induced liver fibrosis in rats | Li et al. 2006c |
| Acidic polysaccharides | Cultured C. militaris | Anti-influenza virus activity | 0.1 mg/15 μL/mouse, intranasal treatment | Decreased virus titers in BALF and the lungs of mice infected with influenza A virus and increased survival rate; increased TNF-α and IFN-γ levels in mice | Ohta et al. 2007 |
| 1–;1000 μg/mL | Enhanced NO production, induced iNOS mRNA,iNOS protein, and IL-1β, IL-6, IL-10, and TNF-α mRNA in RAW 264.7 cells | ||||
| CO-N (33 kDa) | Polysaccharide fraction of C. ophioglosoides | Diagnosis of active Wegener’s granulomatosis | N/A | Reacted with sera from patients with some collagen diseases | Ikeda et al. 1993 |
| Anticancer | N/A | Inhibited the proliferation of sarcoma 180 cells and the growth of a syngeneic solid tumor (MM46 mammary carcinoma) in vivo and exhibited cytotoxicity against IMC and P388D1 cells in vitro | Ohmori et al.1989 | ||
| Diphenyl Ethers | |||||
| Violaceol-I and -II | Cultured broth of Cordyceps sp. BCC 1861 | Antitumor activity | N/A | Showed cytotoxicity against KB, BC, NCI-H187,and Vero cancer cells with IC50 of 6.36, 5.50, 3.70, and 1.3 μg/mL, respectively | Bunyapaiboonsri et al. 2007 |
| Antimicobacterial activity | N/A | Antimalarial with IC50 of 3.38 μg/mL; antituberculous activity with MIC of 200 μg/mL | |||
| Cordyol C | Cultured broth of Cordyceps sp. BCC 1861 | Antitumor activity | N/A | Showed cytotoxicity against BC, NCI-H187, and Vero cancer cells with IC50 of 8.65, 3.72, and 13.1 μg/mL, respectively | Bunyapaiboonsri et al. 2007 |
| Antimicobacterial activity | N/A | Antituberculous activity with MIC of 200 μg/mL;anti-HSV-1 with IC50 of 1.3 μg/mL | |||
| Diocinol | Antitumor activity | N/A | Showed cytotoxicity against BC and Vero cancer cells with IC50 of 13.46 and 18.6 μ/mL, respectively | Bunyapaiboonsri et al. 2007 | |
| Antimicobacterial activity | N/A | Antituberculous activity with MIC of 50 μg/mL | |||
| Cordyol A | Antimicobacterial activity | N/A | Antituberculous activity with MIC of 100 μg/mL | Bunyapaiboonsri et al. 2007 | |
| Alkaloids | |||||
| Cordyformamide | C. brunearubra BCC1395 | Antimalarial activity | N/A | Against malarial parasite with an IC50 value of 18 μM | Isaka et al.2007 |
| Anticancer activity | N/A | Against BC, KB, NCI-H187, and noncancerous with IC50 of 39, 56, 56, and 140 μM, respectively | |||
| Cordypyridone A | Mycelium of C. nipponicaBCC 1389 | Antimalarial activity | N/A | In vitro antimalarial activity with IC50 values of 0.066 μg/mL | Isaka et al.2001 |
| Cordypyridone B | Mycelium of C. nipponica BCC 1389 | Antimalarial activity | N/A | In vitro antimalarial activity with IC50 values of 0.037 μg/mL | Isaka et al.2001 |
| Militarinone A | Neurotrophic effect | 10 μM | Had a pronounced neurotrophic effect in PC-12 cells | Schmidt et al. 2002 | |
| Militarinone B | Mycelium of Paecilomyces militaris (anamorph of C. militaris) | Neurotrophic effect | N/A | Had a pronounced neurotrophic effect in PC-12 cells | |
| Militarinone C | Neurotrophic effect | N/A | Had a pronounced neurotrophic effect in PC-12 cell | Schmidt et al.2003 | |
| Militarinone D | Anticancer activity | N/A | Had cytotoxicity in PC-12 cells | ||
| (+)-N-deoxymilitarinone A | P. farinosus RCEF 0097 | Neurotrophic effect | 33–100 μM | Induced neurite sprouting in PC-12 cells | Cheng et al.2006 |
| Anticancer activity | 100 μM | A cytotoxic effect was observed in human neurons (IMR-32) | |||
| Farinosones A | P. farinosus RCEF 0101 | Neurotrophic effect | 50 μM | Induced neurite outgrowth in the PC-12 cell line | Cheng et al.2004 |
| Farinosones A | Neurotrophic effect | 50 μM | Induced neurite outgrowth in the PC-12 cell line | ||
| (3R,6R)-4-methyl-6-(1-methylethyl)-3-phenylmethylperhydro-1,4-oxazine-2,5-dione | Fruiting bodies of Isaria japonica | Anticancer activity | 5–100 μg/mL | Induced apoptotic cell death of human leukemia cells (HL-60) | Oh et al. 2002 |
| Proteins | |||||
| Hemagglutinin (30 kDa) | C. militaris | Anticancer and anti-HIV | 0.0–1.2 mg/mL | Exhibited some antiproliferative activity to HepG2 cell; inhibited HIV-1 reverse transcriptase (IC50 = 10 μM) | Wong, Wang, and Ng 2009 |
| CML (lectin, 31 kDa) | Ascomycete C. militaris | Hemagglutination and mitogenic activity | 0.01μ4.0 _M | Exhibited hemagglutination activity in mouse and rat erythrocytes, but not in human ABO erythrocytes; exhibited mitogenic activity against mouse splenocytes | Jung et al. 2007 |
| Beauvericin | C. dicadae, P.tenuipes,C. takaomanlana | Anticancer activity | 0.1–300.0 _M | Exerted cytotoxic effects on U937 and HL-60 cells | Cal/ et al. 2004 |
| Cordycedipeptide A | Culture liquid of C. sinensis (Berk.) Sacc. | Anticancer activity | N/A | Had cytotoxic activities to L-929, A375, and Hela with IC50 values of 6.37, 4.69, and 12.71 μg/mL, respectively | Jia et al. 2005 |
| Cordyheptapeptide A | Cordyceps sp. BCC 1788 | Anticancer activity | N/A | Showed cytotoxicity against Vero cells | Rukachaisirikul et al. 2006 |
| CSP (protease, 31 kDa) | Culture supernatant of C. sinensis | Fibrinolytic activity | 0.5 mg/mL (0.2 μL) | Hydrolyzed fibrinogen, fibrin, and casein with a high efficiency, while hydrolyzing BSA and human serum albumin (HSA) to a lesser extent | Li et al. 2007 |
| Enzyme (52 kDa) | Fruiting bodies of cultured C. militaris | Fibrinolytic activity | 10 μL (0.64 mg/mL) | Hydrolyzed the fibrin α-chain followed by the γ-γ chains and the β-chain | Kim et al. 2006 |
| 10 μg | Exhibited fibrinogenolytic activity by rapidly hydrolyzing the fibrinogen Aμ, Bβ, and γ chains | ||||
| P-Terphenyls | |||||
| Gliocladinin A | Solid cultures of Gliocladium sp. that colonizes C. sinensis | Anticancer activity | N/A | Inhibited the proliferation of Hela and HCT116 with IC50 of 54 and more than 270 μM, respectively | Guo et al. 2007 |
| Antimicrobial activity | N/A | Showed activity against Staphylococcus aureuswith MIC values of 270 μM | |||
| Gliocladinin B | Solid cultures of Gliocladium sp. that colonizes C. sinensis | Anticancer activity | N/A | Inhibited the proliferation of Hela and HCT116 with IC50 of 40 and 80–100 μM, respectively | Guo et al. 2007 |
| Antimicrobial activity | N/A | Showed activity against S. aureus with MIC values of 130 μM | |||
| Naphthoquinones | |||||
| Erythrostominone | The culture of C. unilateralis BCC1869 | Antimalarial activity | N/A | Showed antimalarial activity with IC50 of 4.0 μg/mL, and cytotoxic activity on BC, KB, and Vero cells with IC50 of 9.7, 23.0, and 15.0 μg/mL, respectively | Kittakoop et al.1999 |
| Deoxyerythrostominone | Showed antimalarial activity with IC50 of 7.5 μg/mL, and cytotoxic activity on BC, KB, and Vero cells with IC50 of 6.0, 12.4, and ca30 μg/mL, respectively | ||||
| 4-O-methyl erythrostominone | Showed antimalarial activity with IC50 of 10.1 μg/mL, and cytotoxic activity on BC, KB, and Vero cells with IC50 of ca5, 24.0, and ca10 μg/mL, respectively | ||||
| Epierythrostominol | Showed antimalarial activity with IC50 of 7.0 μg/mL, and cytotoxic activity on BC, KB, and Vero cells with IC50 of 4.2, 7.2, and 7.5 μg/mL, repectively | ||||
| Deoxyerythrostominol | Showed antimalarial activity with IC50 of 8.5 μg/mL, and cytotoxic activity on BC, KB, and Vero cells with IC50 of ca10, 20, and 10 μg/mL, repectively | ||||
| 3,5,8-Trihydroxy-6-methoxy-2-(5-oxohexa-1,3-dienyl)-1,4-naphthoquinone | Antimalarial activity | Showed antimalarial activity with IC50 of 2.5 μg/mL | |||
Note: p.o.: per os, oral administration; i.p.: intraperitoneal administration; i.v.: intravenous injection; s.c.: subcutaneous injection; N/A: unknown.
From: Chapter 5, Cordyceps as an Herbal Drug
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