ABSTRACT
Objective To investigate the mocelualr mechanism of Cordycepin negative modulates LPSinduced cytokine production in murine macrophages.Methods The RAW264.7 murine macrophages were cultured in vitro and were pre-treated by different concentration of Cordycepin,and then stimulated by LPS for 8 h.Production of TNF-o,IL-6 and IL-12,and the content of p65 in the nuclear were detected by ELISA.Expression of heme oxygenase-1 (HO-1) and phosphorylation of IκB and p38 were measured by Western blot.Nuclear translocation of Nrf2 was detected by Immunofluorescence.Results 1 ～ 30 μg/mL of Cordycepin treatment significantly abrogated LPS-induced TNF-α,IL-6 and IL-12 production,p65 nuclear translocation and IκB phosphorylation.In addition,different concentration of Cordycepin could also induce RAW264.7 cells expression of HO-1,phosphorylation of p38 and nuclear translocation of Nrf2.Application of p38 inhibitor and small interfering RNA-mediated knock-down of Nrf-2 significantly inhibited surfactin-induced HO-1 expression.Treatment with a selective inhibitor of HO-1 reversed the Cordycepin mediated inhibition of pro-inflammatory cytokines.Conclusions Cordycepin induces antiinflammatory effects by inhibition of NF-κB and activation of Nrf-2 and p38 mediated HO-1 induction.