The Study of Cordycepin Activities and Cellular Mechanisms during Microglial Activation

Cordycepin is an adenosine analogue, is one of the major bioactive components of C. militaris. It has been shown to have pharmacological, immunological stimulating, anti-cancer, and anti-inflammatory activities.Cells have receptors for adenosine, which can raise and speed up metabolism of cells. Because adenosine receptors play a role in the production of testosterone in Leydig cells, the researchers decided to test this substance on mice and the testosterone producing Leydig cells of mice. Now it looks as though researchers at Hung Kuang University in Taiwan have worked out at least which active ingredient in Cordyceps is responsible for the rise in testosterone: cordycepin Cordycepin has displayed cytotoxicity against some leukemic cell lines in vitro.

Cordycepin activities and cellular mechanisms during microglial activation have yet to be elucidated. Thus, Jin-Woo Jeong and his group evaluated the anti-inflammatory effect of cordycepin on the production of inflammatory mediators in lipopolysaccharide (LPS)-stimulated murine BV2 microglia. We also investigated the effects of cordycepin on LPS-induced nuclear factor-kappaB (NF-κB) activation and on phosphorylation of mitogen-activated protein kinases (MAPKs). After LPS stimulation, nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokine production was detected in BV2 microglia. However, we found that cordycepin significantly inhibited the excessive production of NO, PGE2, and pro-inflammatory cytokines in a concentration-dependent manner without causing cytotoxicity. In addition, cordycepin suppressed NF-κB translocation by blocking IkappaB-α (IκB-α) degradation and inhibited the phosphorylation of Akt, ERK-1/2, JNK, and p38 kinase. Our results indicate that the inhibitory effect of cordycepin on LPS-stimulated inflammatory mediator production in BV2 microglia is associated with the suppression of the NF-κB, Akt, and MAPK signaling pathways. Therefore, cordycepin may be useful in treating neurodegenerative diseases by inhibiting inflammatory mediator production in activated microglia.

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