逍遥散调控海马NLRP3炎症小体通路抗抑郁药效的机制研究OA

Objective To investigate the antidepressant effects of Xiaoyao Powder(逍遥散,XYP),a classical traditional Chinese medicine(TCM)prescription,on chronic restraint stress(CRS)-induced depressive-like behaviors in mice and its regulatory effects on the NLRP3 inflammasome signaling pathway in the hippocampus.Methods Depressive-like behaviors in mice were evaluated using behavioral tests,including the open field test(OFT),tail suspension test(TST),forced swim test(FST),and sucrose preference test(SPT).The expression of key inflammatory markers in the hippocampus was assessed via quantitative PCR(qPCR)for Nlrp3,Il-18,Il-1β,Arg1,Cd206,Cd86,Inos,Pparg,and Ppargc1a,as well as Western blot(WB)for NLRP3,cleaved-Caspase-1/Caspase-1,IL-1β,ASC,and PPARγ.Results Mice in the CRS group exhibited pronounced depressive-like behaviors compared to the control group.Treatment with XYP or fluoxetine significantly ameliorated these behavioral abnormalities.qPCR analysis revealed that XYP markedly suppressed the hippocampal expression of the pro-inflammatory markers Nlrp3,Il-18,Il-1β,and M1 microglial markers Cd86 and Inos,while restoring the expression of M2 markers Arg1 and Cd206,as well as nuclear receptor Pparg and its coactivator Ppargc1a.Furthermore,XYP administration effectively inhibited the activation of the NLRP3/Caspase-1/ASC inflammasome pathway and the expression of IL-1β while enhancing PPARγ levels.Conclusion These findings suggest that XYP exerts antidepressant effects by modulating the Hippocampal NLRP3 inflammasome and associated signaling pathways.This study provides novel mechanistic insights and experimental evidence for supporting the clinical application of XYP in the treatment of depression.