Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-[kappa]B and Jak2-Stat3 Signaling Pathways

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 purpose...

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Published inPloS one Vol. 11; no. 2
Main Authors Song, Fangjiao, Zeng, Kewu, Liao, Lixi, Yu, Qian, Tu, Pengfei, Wang, Xuemei
Format Journal Article
LanguageEnglish
Published Public Library of Science 26.02.2016
Subjects
Development and progression
Genetic aspects
Inflammation
Lignin
Microglia
Neurodegenerative diseases
Physiological aspects
Risk factors
China
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Summary: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)-[alpha] 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-IKK[beta]-NF-[kappa]B 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-IKK[beta]-NF-[kappa]B and Jak2-Stat3 signaling pathways.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0149991