Anti-inflammatory effects of cordycepin via suppression of inflammatory mediators in BV2 microglial cells

Int Immunopharmacol. 2010 Dec;10(12):1580-6. doi: 10.1016/j.intimp.2010.09.011. Epub 2010 Oct 14.


Cordyceps militaris, a traditional medicinal mushroom, produces the bioactive compound cordycepin (3'-deoxyadenosine). Although cordycepin has been shown to have pharmacological, immunological stimulating, anti-cancer, and anti-inflammatory activities, its activities and cellular mechanisms during microglial activation have yet to be elucidated. Thus, we 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cytokines / antagonists & inhibitors
  • Cytokines / immunology
  • Deoxyadenosines / pharmacology*
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / immunology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / drug effects*
  • Microglia / immunology*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / immunology
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / immunology
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / immunology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects


  • Anti-Inflammatory Agents
  • Cytokines
  • Deoxyadenosines
  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • cordycepin
  • Dinoprostone