Reynosin protects neuronal cells from microglial neuroinflammation by suppressing NLRP3 inflammasome activation mediated by NADPH oxidase  

作　　者：YANG Yanqiu CHE Yue FANG Mingxia YAO Xiaohu ZHOU Di WANG Feng CHEN Gang LIANG Dong LI Ning HOU Yue 

机构地区：[1]Key Laboratory of Bioresource Research and Development of Liaoning Province,College of Life and Health Sciences,North-eastern University,Shenyang 110000,China [2]National Frontiers Science Center for Industrial Intelligence and Systems Optimization,Key Laboratory of Data Analytics and Optimization for Smart Industry,Ministry of Education,Northeastern University,Shenyang 110000,China [3]School of Traditional Chinese Materia Medica,Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning province,Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang City,Shenyang Pharmaceutical University,Shenyang 110000,China [4]State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources,School of Chemistry and Pharmaceutical Sciences,Guangxi Normal University,Guilin 541000,China

出　　处：《Chinese Journal of Natural Medicines》2024年第6期486-500,共15页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82174076);the Construction Project of Liaoning Provincial Key Laboratory,China(No.2022JH13/10200026);the Fundamental Research Funds for the Central Universities(No.N2220002),the 111 Project(No.B16009);Scientific Research Fund of Liaoning Province Education Department(No.LJKZ0945);Natural Science Foundation of Liaoning Province(No.2022-MS-242).

摘　　要：Neuroinflammation,mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3(NLRP3)inflammasome,is a significant contributor to the pathogenesis of neurodegenerative diseases(NDDs).Reynos-in,a natural sesquiterpene lactone(SL),exhibits a broad spectrum of pharmacological effects,suggesting its potential therapeutic value.However,the effects and mechanism of reynosin on neuroinflammation remain elusive.The current study explores the effects and mechanisms of reynosin on neuroinflammation using mice and BV-2 microglial cells treated with lipopolysaccharide(LPS).Our findings reveal that reynosin effectively reduces microglial inflammation in vitro,as demonstrated by decreased CD11b expression and lowered interleukin-1 beta(IL-1β)and interleukin-18(IL-18)mRNA and protein levels.Correspondingly,in vivo,results showed a re-duction in the number of Iba-1 positive cells and alleviation of morphological alterations,alongside decreased expressions of IL-1βand IL-18.Further analysis indicates that reynosin inhibits NLRP3 inflammasome activation,evidenced by reduced transcription of NLRP3 and caspase-1,diminished NLRP3 protein expression,inhibited apoptosis-associated speck-like protein containing a CARD(ASC)oli-gomerization,and decreased caspase-1 self-cleavage.Additionally,reynosin curtailed the activation of nicotinamide adenine dinuc-leotide phosphate(NADPH)oxidase,demonstrated by reduced NADP^(+)and NADPH levels,downregulation of gp91^(phox) mRNA,pro-tein expression,suppression of p47^(phox) expression and translocation to the membrane.Moreover,reynosin exhibited a neuroprotective effect against microglial inflammation in vivo and in vitro.These collective findings underscore reynosin’s capacity to mitigate mi-croglial inflammation by inhibiting the NLRP3 inflammasome,thus highlighting its potential as a therapeutic agent for managing neuroinflammation.

关 键 词：MICROGLIA NLRP3 inflammasome Reactive oxygen species NADPH oxidase Neuron Reynosin 

分 类 号：R965[医药卫生—药理学]