title: Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways.
abstract: Microglial-mediated neuroinflammation has been established as playing a vital role in pathogenesis of neurodegenerative disorders. Thus, rational regulation of microglia functions to inhibit inflammation injury may be a logical and promising approach to neurodegenerative disease therapy. The purposes of the present study were to explore the neuroprotective effects and potential molecular mechanism of Schizandrin A (Sch A), a lignin compound isolated from Schisandra chinesnesis. Our observations showed that Sch A could significantly down-regulate the increased production of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)-6 induced by lipopolysaccharide (LPS) both in BV-2 cells and primary microglia cells. Moreover, Sch A exerted obvious neuroprotective effects against inflammatory injury in neurons when exposed to microglia-conditioned medium. Investigations of the mechanism showed the anti-inflammatory effect of Sch A involved the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression levels and inhibition of the LPS-induced TRAF6-IKKβ-NF-κB pathway. Furthermore, inhibition of Jak2-Stat3 pathway activation and Stat3 nuclear translocation also was observed. In conclusion, SchA can exert anti-inflammatory and neuroprotective effects by alleviating microglia-mediated neuroinflammation injury through inhibiting the TRAF6-IKKβ-NF-κB and Jak2-Stat3 signaling pathways.
authors.affiliation: Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing, 100034, China.
authors.forename: Fangjiao
authors.initials: F
authors.lastname: Song
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Kewu
authors.initials: K
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Lixi
authors.initials: L
authors.lastname: Liao
authors.affiliation: Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing, 100034, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
authors.affiliation: Research Studio of Integration of Traditional and Western Medicine, First Hospital, Peking University, Beijing, 100034, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D034242:Cyclooctanes / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism*; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D000066829:Neuroprotection / Q000187:drug effects; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism*
chemical_list: D034242:Cyclooctanes; D018836:Inflammation Mediators; D017705:Lignans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011083:Polycyclic Compounds; D050796:STAT3 Transcription Factor; D048029:TNF Receptor-Associated Factor 6; C034734:schizandrin A; D053614:Janus Kinase 2