title: Gomisin A inhibits lipopolysaccharide-induced inflammatory responses in N9 microglia via blocking the NF-κB/MAPKs pathway.
abstract: 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-α, IL-1β 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)-κB 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-κB and MAPKs signaling pathways.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Development and Utilization Key Laboratory of Northeast Plant Materials of Liaoning Province, Department of Pharmacognosy, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Lijia
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Guoning
authors.initials: G
authors.lastname: Lian
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: zhaosiqi2010@gmail.com.
authors.forename: Siqi
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Chunming
authors.initials: C
authors.lastname: Wang
authors.affiliation: Development and Utilization Key Laboratory of Northeast Plant Materials of Liaoning Province, Department of Pharmacognosy, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: yinjun826@sina.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: wucf@syphu.edu.cn.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China. Electronic address: yangjingyu2006@gmail.com.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D034242:Cyclooctanes / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004149:Dioxoles / Q000494:pharmacology*; D004789:Enzyme Activation; D017705:Lignans / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D034242:Cyclooctanes; D016207:Cytokines; D017931:DNA Primers; D004149:Dioxoles; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C033585:schizandrol B; D019255:NADPH Oxidases; D015232:Dinoprostone
keywords: Gomisin A; LPS; MAPKs; Microglia; NF-κB; ROS