Wogonin Attenuates Endotoxin-Induced Prostaglandin E2 and Nitric Oxide Production via Src-ERK1/2-NFκB Pathway in BV-2 Microglial Cells

Microglia are the major component of intrinsic brain immune system in neuroinflammation. Although wogonin expresses anti-inflammatory function in microglia, little is known about the molecular mechanisms of the protective effect of wogonin against microglia activation. The aim of this study was to evaluate how wogonin exerts its anti-inflammatory function in BV2 microglial cells after LPS/INF gamma administration. Wogonin not only inhibited LPS/INF gamma-induced PGE2 and NO production without affecting cell viability but also exhibited parallel inhibition on LPS/INF gamma-induced expression of iNOS and COX-2 in the same concentration range. While LPS/INF gamma-induced expression of P-p65 and P-I kappa B was inhibited by wogonin-only weak inhibition on P-p38 and P-JNK were observed, whereas it significantly attenuated the P-ERK1/2 and its upstream activators P-MEK1/2 and P-Src in a parallel concentration-dependent manner. These results indicated that the blockade of PGE2 and NO production by wogonin in LPS/INF gamma-stimulated BV2 cells is attributed mainly to interference in the Src-MEK1/2-ERK1/2-NF kappa B-signaling pathway. (C) 2013 Wiley Periodicals, Inc.