Gomisin A inhibits lipopolysaccharide-induced inflammatory responses in N9 microglia via blocking the NF-魏B/MAPKs pathway
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- 作者：Xiaoxiao Wang ; Di Hu ; Lijia Zhang ; Guoning Lian ; Siqi Zhao ; Chunming Wang ; Jun Yin ; Chunfu Wu ; Jingyu Yang
- 关键词：Gomisin A ; Microglia ; LPS ; NF-魏B ; MAPKs ; ROS
- 刊名：Food and Chemical Toxicology
- 出版年：January, 2014
- 年：2014
- 卷：63
- 期：Complete
- 页码：119-127
- 全文大小：2282 K
文摘
Gomisin A, one of the major dibenzocyclooctadiene lignans isolated from Schisandra chinensis Baill., has proved to possess a variety of pharmacological effects. The aim of the present study was to investigate the anti-inflammatory and neuroprotective effects of gomisin A as well as its potential molecular mechanisms. It was found that gomisin A not only inhibited the production of NO and PGE2 in a concentration-dependent manner but also suppressed the expressions of iNOS and COX-2 in LPS-stimulated N9 microglia without observable cytotoxicity. Gomisin A was also able to attenuate the mRNA expression and the production of pro-inflammatory factors TNF-伪, IL-1尾 and IL-6. Moreover, LPS induced reactive oxygen species (ROS) production, NADPH oxidase activation, and gp91phox expression, which were markedly inhibited by gomisin A in microglia. Furthermore, the data showed that gomisin A significantly down-regulated the TLR4 protein expression, and inhibited nuclear transcription factor (NF)-魏B and mitogen-activated protein kinases (MAPKs) signaling pathways. Additionally, gomisin A alleviated the cell death of SH-SY5Y neuroblastoma, rat primary cortical and hippocampal neurons induced by the conditioned-media from activated microglia. In summary, gomisin A may exert neuroprotective effects by attenuating the microglia-mediated neuroinflammatory response via inhibiting the TLR4-mediated NF-魏B and MAPKs signaling pathways.