Paeoniflorin alleviates depression by inhibiting the activation of NLRP3 inflammasome via promoting mitochondrial autophagy  

作　　者：SU Lili GUO Pengli GUO Xiangjuan HE Zhongmei ZHAO Yan ZONG Ying LI Jianming CHEN Weijia DU Rui 

机构地区：[1]College of Chinese Medicinal Materials,Jilin Agricultural University,Changchun 130118,China [2]Jilin Provincial Engineering Research Center for Efficient Breeding and Product Development of Sika Deer,Changchun 130118,China [3]Key Laboratory of Animal Production and Product Quality and Security,Ministry of Education,Ministry of National Education,Changchun 130118,China

出　　处：《Chinese Journal of Natural Medicines》2024年第6期515-529,共15页中国天然药物（英文版）

基　　金：supported by the Jilin Science&Technology Development Plan(Nos.20210204001YY,20200404090YY);Jilin Province aid Project for Xinjiang Uygur Autonomous Region(No.0207-202020043).

摘　　要：Depression ranks among the most common neuropsychiatric disorders globally.Current studies examining the roles of inflammation and mitochondrial autophagy in the antidepressant efficacy of paeoniflorin(PF)are sparse.This study aimed to elucidate PF’s antidepressant mechanism by promoting autophagy and inhibiting NLRP3 inflammasome activation using chronic unpredictable mild stimulation(CUMS)-induced C57BL/6 mouse models in vivo and corticosterone(CORT)-induced HT22 cell models in vitro.Results demonstrated that PF enhanced the viability of HT22 cells following CORT exposure,restored mitochondrial membrane poten-tial(MMP),reduced reactive oxygen species accumulation,increased LC3 fluorescence intensity,and suppressed inflammatory cy-tokine secretion and inflammation activation.Additionally,PF ameliorated depressive behaviors induced by CUMS and improved damage in hippocampal neurons.It also reduced the expression of NLRP3,ASC,Caspase-1,IL-1β,and the assembly of the NLRP3 in-flammasome.Moreover,PF upregulated the expression of autophagy-related proteins in the hippocampus,facilitating the clearance of damaged mitochondria and enhancing autophagy.The role of autophagy in PF’s antidepressant effects was further confirmed through the use of the autophagy inhibitor 3-methyladenine(3-MA),which reduced the efficacy of PF.In conclusion,PF effectively improved depressive behaviors in CUMS-induced mice and reduced NLRP3-mediated inflammation both in vivo and in vitro,likely via the in-duction of autophagy.

关 键 词：PAEONIFLORIN DEPRESSION AUTOPHAGY NLRP3 inflammasome 

分 类 号：R965[医药卫生—药理学]