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/INFγ administration. Wogonin not only inhibited LPS/ INFγ-induced PGE2 and NO production without affecting cell viability but also exhibited parallel inhibition on LPS/INFγ-induced expression of iNOS and COX-2 in the same concentration range. While LPS/INFγ-induced expression of P-p65 and P-IκB 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/INFγ-stimulated BV2 cells is attributed mainly to interference in the Src-MEK1/2-ERK1/2-NFκB-signaling pathway.
Department of Neurology, Show Chwan Memorial Hospital, Changhua, Taiwan, Republic of China.
Chung-Hsin
CH
Yeh
Ming-Ling
ML
Yang
Chien-Ying
CY
Lee
Ching-Ping
CP
Yang
Yi-Ching
YC
Li
Chun-Jung
CJ
Chen
Yu-Hsiang
YH
Kuan
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000276:immunology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology*; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D019061:src-Family Kinases / Q000276:immunology
D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D007371:Interferon-gamma; D019061:src-Family Kinases; D015232:Dinoprostone; C085514:wogonin
MEK1/2-ERK1/2; NFκB; Src; microglia; wogonin