TABLE 3.
Mechanism of action of the Cordyceps spp.-induced pharmacological activities.
| Pharmacological activity | Mechanism of action | References |
|---|---|---|
| Immunomodulatory and anti-inflammatory activities | •Augmented the in vivo and in vitro NK activities phagocyte reactions via the activation of macrophages •Modulation of IL-6 production activated macrophages and enhance secretion of hematopoietic growth factors such as GM-CSF •Modulation of cytokines •Increase in an acid phosphatase activity, representing lysosomal enzymes, in macrophages •Inducing the expression of cytokines like IFN-γ, IL-12, and TNF- α •Increased TNF-α and IFN-γ, enhanced NO production, and induced iNOS mRNA and protein expressions in macrophage. Induction of mRNA expression of IL-1β, IL-6, IL-10, and TNF-α •Modulation of transcription factors involved in the gene regulation of various cytokines. •Upregulated the expression of TNF-α, IFN-γ, IL-6, and IL-1β •Stimulate NO production, phagocytosis, respiratory burst activity, secretion of IL-1β and IL-2 of macrophages •The decrement in iNOS expression in macrophages •Inhibited the phosphorylation of Akt, IκBα, and p38. Suppressed TNF-α, COX-2, iNOS, and translocation of NF-κB in macrophages •Inhibitory effects on the production of inflammatory mediators •Inhibition of IκB/NF-κB pathway and suppression of JNK and p38 activation •Suppresses the production NO, iNOS, and pro-inflammatory cytokines in macrophages via inhibition of NF-κB and AP-1 |
(Xu et al., 1992; Koh et al., 2002; Shin et al., 2003; Yu et al., 2004; Won and Park, 2005; Chen et al., 2006; Kim et al., 2006; Kuo et al., 2007; Ohta et al., 2007; Zhou et al., 2008; Zhu L et al. (2014); Kim T W et al. (2014); Park et al., 2014; Yang et al., 2015a; Chiu et al., 2016b; Liu et al., 2016; Jung et al., 2019) |
| Antioxidant and antiaging activity | •Inhibited MDA formation, anti-lipid peroxidation action and inhibited the accumulation of cholesteryl ester in macrophages •Attenuating the changes of GPx and SOD activities, inhibited MDA formation •Modulating antioxidation activity via significantly enhancing SOD activity of liver, brain, and serum as well as GPx activity of liver and brain in tumor-bearing mice •Improve the activity of SOD of RBCs, brain and liver, the activity of na+-K+-ATPE of the brain, the activity of catalase and GPx of blood, decrease the activity of monoamine oxidase of the brain and the contents of MDA of brain and liver in aged mice. •Improved the activity of SOD, glutathione peroxidase and catalase and lowered the level of lipid peroxidation and monoamine oxidase activity |
(Yamaguchi et al., 2000a; Gu et al., 2003; Wang et al., 2004; Chen et al., 2006; Ji et al., 2009; Wang M et al. (2012) |
| Antitumor effects | •Via immunomodulation •Stimulating adenosine A3 receptors, Wnt signaling pathway, GSK3β activation cyclin D1 inhibition •Caspase activation and mitochondrial dysfunction •Via mTOR and AMPK signaling •Enhancing JNK and p38 kinase activity and activity of Bcl-2 pro-apoptotic molecules •Downregulating MDR/HIF-1α via AMPK/mTORC1 signaling •Antiangiogenic via inhibiting tube formation in endothelial cells and MMP reduction •Regulating Bcl-2 family and caspase activity and inhibition of COX-2 and prostaglandin E2 accumulation •Regulation of p85/Akt-dependent or GSK3β-related caspase-3-dependent apoptosis •Involvement of hedgehog, apoptosis, p53, and estrogen signaling |
(Yoshida et al., 1989; Yoo et al., 2004; Park et al., 2005; Yoshikawa et al., 2007; Jin et al., 2008; Yoshikawa et al., 2008; He et al., 2010; Wong et al., 2010; Jen et al., 2011; Wu et al., 2014; Park et al., 2017; Lee et al., 2019) |
| Hypoglycemic activity | •Potentiated the activities of glucokinase, hexokinase and glucose-6-phosphate dehydrogenase •Increased the activity of hepatic glucokinase, the decline in the protein content of facilitative GLUT2 •By enhancing insulin sensitivity and improving oral glucose tolerance •Stimulates the expression of HNF-1α to activate GLUT2 for glucose uptake, induced AMPK phosphorylation, and gluconeogenesis inhibition •anti-PTP1B activity |
(Kiho et al., 1996; Kiho et al., 1999; Balon et al., 2002; Zhao et al., 2002; Kim et al., 2017; Sun et al., 2019) |
| Hypocholesterolemic, hypotensive and vasorelaxation activities | •The endothelium-dependent vasorelaxant effect through stimulating the production of nitric oxide and endothelium-derived hyperpolarizing factor •anti-lipid peroxidation activities and inhibit the accumulation of cholesteryl ester in macrophages via suppression of LDL oxidation •Inhibiting LDL oxidation through scavenging free radicals •Increased the HDL cholesterol level, but decreased VLDL LDL cholesterol level •Inhibited PDGF-BB-induced RASMCs migration and proliferation via interfering with adenosine receptor-mediated NOS pathways •Reduced serum total cholesterol, triglyceride, LDL-C, VLDL-C as well as LDL-C/HDL-C and TC/HDL-C ratios. Increase in lipoprotein lipase (LPL) and hepatic lipase (HL) activity •Increase in levels of serum insulin •Reduction in the levels of blood and liver lipid, and improvement of the glutamate pyruvate transaminase and antioxidant activity |
Yamaguchi et al., 2000a; Yamaguchi et al., 2000b; Chiou et al., 2000; Koh et al., 2003; Won et al., 2009; Gao et al., 2011; Guo et al., 2011; Wang L et al. (2015) |
| Anti-fatigue and antidepressant activity | •Facilitating efficient oxygen utilization, enhance energy metabolism in the mitochondria •The increasing level of β-ATP •Increased the metabolic threshold and the ventilatory threshold of the subjects •Extended the exhaustive swimming time of mice, hepatic and muscle glycogen levels, and decrease the blood lactic acid and blood urea nitrogen (BUN) levels •Upregulation of skeletal metabolic regulators AMPK, PGC-1 and PPAR- as well as activation of NRF-2-ARE pathway •Reducing the accumulation of blood lactic acid level. •Via decreasing MDA and 8-OHdG levels and increasing antioxidant enzymes activities (SOD, catalase and GPx) in the serum, liver and muscle of mice •Activating AMPK and protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways and regulating serum hormone level |
(Zhang et al., 1995; Xiao et al., 1999; Dai et al., 2001; Li and Li, 2009; Chen S et al. (2010); Kumar et al., 2011; Yan et al., 2012; Yan et al., 2013; Song et al., 2015; Geng et al., 2017) |
| Aphrodisiac potential | •PKC, cAMP-protein kinase A signal pathway •Induce the expression of steroidogenic acute regulatory (StAR) protein •Induce in vivo plasma corticosterone level •adenosine receptors activated cAMP-PKA-StAR pathway •PLC/PKC and MAPK signal transduction pathways •Stimulating CYP11A1, 3β-HSD, and CYP17A1 expressions |
Wang et al. (1998), Huang et al. (2000), Hsu et al. (2003a), Hsu et al. (2003b), Huang B M et al. (2004), Chen et al. (2005), Leu et al. (2005), Chen S et al. (2010), Leu et al. (2011), Pao et al. (2012), Wang et al. (2016) |
Footnote: DC-SIGN, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; ERK, 1/2 extracellular signal-related kinases one and two; IL, interleukin; JNK, c-jun NH2-terminal kinase; MAPK, mitogen-activated protein kinase; MGL, macrophage galactose-type C-type lectin; MR, mannose receptor; MyD88, myeloid differentiation primary response protein 88; NF-κB, nuclear factor ‘kappa-light-chain-enhancer’ of activated B cells; P38, mitogen-activated protein kinase; PI3K, phosphatidylinositol 3-kinase; RAF, rapidly accelerated fibrosarcoma; RAS, rat sarcoma; SOCS, suppressor of cytokine signaling; SYK, Spleen tyrosine kinase; Th2, T helper type 2; TLR, toll-like receptor; Treg, regulatory T cells; TRIF, TIR domain-containing adapter inducing IFN-β.