Abstract:

Objective: To evaluate the inhibition of cordycepin on microglial activation induced by lipopolysaccharide (LPS)
and the protection of neuronal cells by cordycepin. Methods: The effect of cordycepin (0.1–10 μmol/L) on cell viability was
evaluated by MTT assay. Nitrite levels in culture supernatants were examined by Griess assay. The mRNA expression of
inducible nitric oxide synthase (iNOS) was evaluated by RT-PCR. The NO-scavenging and DPPH free radical-scavenging
activities of cordycepin were measured using SNP as a NO donor and DPPH as a free radical donor, respectively. The effect
of cordycepin on the decreased viability of PC12 neurons induced by H2O2 or conditioned medium obtained from LPSactivated
microglial cells was evaluated by MTT assay. In addition, the superoxide dismutase (SOD) activity was examined
by hydroxylamine method. Results: Cordycepin could inhibit the production of NO and the mRNA expression of iNOS
in LPS-activated primary mouse microglial cells obviously. However, treatment with cordycepin (0.1–10 mol/L) had no
significant cytotoxicity. Cordycepin showed significant scavenging activity towards nitric oxide radical (NO) and DPPH free
radicals. Cordycepin alone did not influence the viability of PC12 neurons; however, it improved the decreased viability of
PC12 neurons induced by H2O2 or conditioned medium from LPS-activated microglia. In addition, the SOD activity in H2O2-
treated PC12 cells could be upgraded. Conclusion: It is suggested that cordycepin can inhibit LPS-induced NO production
by blocking the transcriptional levels of iNOS in microglial cells. Cordycepin can protect PC12 neurons from toxic influence
by activated microglia, and protect H2O2-impaired PC12 cells by improving SOD activity. Cordycepin may have therapeutic
potential for the treatment of neurodegenerative diseases accompanied by microglial activation.

Key words: cordycepin, lipopolysaccharide, microglial activation, nitric oxide, iNOS, neuroprotection