18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

查看全文 作　　者：Qian [1,3]Zhang;Piao [1,3]Luo;Liuhai [3]Zheng;Jiayun [1]Chen;Junzhe [1]Zhang;Huan [1]Tang;Dandan [1]Liu;Xueling [1]He;Qiaoli [1]Shi;Liwei [1]Gu;Jiahao [1]Li;Qiuyan [1]Guo;Chuanbin [3]Yang;Yin Kwan [2]Wong;Fei [1]Xia;Jigang [1]Wang

机构地区：[1]Artemisinin Research Center and Institute of Chinese Materia Medica,Chinese Academy of Chinese Medical Sciences,Beijing,100700,China;[2]Department of Biological Sciences,National University of Singapore,Singapore,117543,Singapore;[3]Department of Geriatrics,Shenzhen People's Hospital(The Second Clinical Medical College,Jinan University),Shenzhen,518020,China

出　　处：《Journal of Pharmaceutical Analysis》索引2022年第12卷第4期,共13页

基　　金：the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-C-202002);the National Key Research and Development Program of China,China(Grant No.:2020YFA0908000);the National Natural Science Foundation of China,China(Grant Nos.:81803389,81903588,32101219,81702580,82074098,81903866,and 81803456);the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ14-YQ-050,ZZ14-YQ-059,ZZ15-ND-10,ZZ15-YQ-063,ZZ14-ND-010,and ZZ14-FL-002). 摘　　要：Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis. 关键词：Glycyrrhetinic acid Hepatic fibrosis PEROXIREDOXIN Reactive oxygen species APOPTOSIS

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18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs

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