Astragaloside IV ameliorates neuroinflammationinduced depressive-like behaviors in mice via the PPARγ/NF-κB/NLRP3 inflammasome axis

Authors: Mei-ting SONG1, Jie RUAN1, Ru-yi ZHANG1, Jie DENG1, Zhan-qiang MA1, Shi-ping MA1
1 Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China
Corresponding to: Zhan-qiang MA:, Shi-ping MA:,
DOI: 10.1038/aps.2017.208
Received: 7 September 2017
Accepted: 31 December 2017
Advance online: 24 May 2018


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 RRS-induced depressive-like behaviors. Furthermore, AS-IV administration significantly reduced the levels of TNF-α and IL-1β, increased PPARγ expression and GSK3β phosphorylation, decreased NF-κB phosphorylation, and reduced NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome and caspase-1 p20 generation in the hippocampus of the mice. LPS-induced depression-like 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-α and IL-1β expression in the mouse hippocampus, which was reversed by administration of AS-IV. Moreover, administration of AS-IV significantly increased PPARγ expression and GSK3β phosphorylation, and decreased NF-κB 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 PPARγ expression.
Keywords: astragaloside IV; depression; PPARγ; GSK3β; NF-κB; NLRP3 inflammasome; neuroinflammation

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