Astragaloside Ⅳ ameliorates neuroinflammation-induced depressive-like behaviors in mice via the PPARy/NF-κB/NLRP3 inflammasome axis

• 来源期刊: 中国药理学报（英文版）
• 关键词: astragaloside Ⅳ depression PPARγ GSK3β NF-κB NLRP3 inflammasome neuroinflammation
• 年，卷（期）: 2018,（10）
• 页码范围: 1559-1570
• 页数: 12页
• 语种: 英文
• DOI: 10.1038/aps.2017.208

摘要

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 PPARy expression and GSK3β phosphorylation,decreased NF-κB 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 depression-like behaviors were induced by LPS injection (1 mg.kg1·d-1,ip),which were ameliorated by administration of AS-Ⅳ (20,40 mg·kg1·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 PPARy expression and GSK3β phosphorylation,and decreasedNF-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 PPARy expression.