期刊
ACTA PHARMACOLOGICA SINICA
卷 39, 期 10, 页码 1559-1570出版社
NATURE PUBL GROUP
DOI: 10.1038/aps.2017.208
关键词
astragaloside IV; depression; PPAR gamma; GSK3 beta; NF-kappa B; NLRP3 inflammasome; neuroinflammation
资金
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- National Natural Science Foundation of China [81573701]
- College Students Innovation Project for the R&D of Novel Drugs [J1310032]
- National Fund for Fostering Talents of Basic Science (NFFTBS)
Major depressive disorder is a common but devastating mental disorder, and recent evidence shows that neuroinflammation may play a pivotal role in the etiology of depression. Astragaloside IV (AS-IV) is an active component purifed from Astragalus membranaceus (Fisch) Bge, which has shown anti-inflammatory, anti-oxidative and anti-apoptotic effects. In this study, we explored whether AS-IV produced antidepressant effects via its inhibition of neuroinflammation in mouse models of depression. Depressive-like behaviors including decreased sucrose consumption, reduced locomotor activity and increased immobility time were induced in mice using repeated restraint stress (RRS). We found that administration of AS-IV (16, 32 and 64 mg.kg(-1).d(-1), ig) significantly attenuated RRSinduced depressive-like behaviors. Furthermore, AS-IV administration significantly reduced the levels of TNF-alpha and IL-1 beta, increased PPAR gamma expression and GSK3 beta phosphorylation, decreased NF-kappa B phosphorylation, and reduced NOD-, LRR- and pyrin domaincontaining protein 3 (NLRP3) inflammasome and caspase-1 p20 generation in the hippocampus of the mice. LPS-induced depressionlike behaviors were induced by LPS injection (1 mg.kg(-1).d(-1), ip), which were ameliorated by administration of AS-IV (20, 40 mg.kg(-1).d(-1), ig). The results of the LPS-induced mouse model were in accordance with those acquired from the RRS-induced mouse model: LPS injection significantly increased TNF-alpha and IL-143 expression in the mouse hippocampus, which was reversed by administration of AS-IV. Moreover, administration of AS-IV significantly increased PPAR gamma expression and GSK3 beta phosphorylation, and decreased NF-kappa B phosphorylation and NLRP3 inflammasome. These results suggest that AS-IV is a potential drug against depression, and its antidepressant effects are partially mediated by inhibition of neuroinflammation via the upregulation of PPAR gamma expression.
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