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 

作者机构：Key Laboratory of Bioresource Research and Development of Liaoning ProvinceCollege of Life and Health SciencesNorth-eastern UniversityShenyang 110000China National Frontiers Science Center for Industrial Intelligence and Systems OptimizationKey Laboratory of Data Analytics and Optimization for Smart IndustryMinistry of EducationNortheastern UniversityShenyang 110000China School of Traditional Chinese Materia MedicaKey Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning provinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110000China State Key Laboratory for Chemistry and Molecular Engineering of Medicinal ResourcesSchool of Chemistry and Pharmaceutical SciencesGuangxi Normal UniversityGuilin 541000China 

出 版 物：《Chinese Journal of Natural Medicines》 (中国天然药物（英文版）)

年 卷 期：2024年第22卷第6期

页      面：486-500页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

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) 

主　　题：Microglia NLRP3 inflammasome Reactive oxygen species NADPH oxidase Neuron Reynosin 

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 ***,the effects and mechanism of reynosin on neuroinflammation remain *** 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 ***,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 *** 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 ***,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 ***,reynosin exhibited a neuroprotective effect against microglial inflammation in vivo and in *** 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.