Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18β-GA)is a natural com-pound 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 18β-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18β-GA inhibited the expression of α-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 reso-nance,we found that 18β-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18β-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 18β-GA in ameliorating hepatic fibrosis,highlighting the future development of 18β-GA as a novel therapeutic drug for hepatic fibrosis.

Qian Zhang;Piao Luo;Liuhai Zheng;Jiayun Chen;Junzhe Zhang;Huan Tang;Dandan Liu;Xueling He;Qiaoli Shi;Liwei Gu;Jiahao Li;Qiuyan Guo;Chuanbin Yang;Yin Kwan Wong;Fei Xia;Jigang Wang

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

药物分析学报（英文）

[1]Qian Zhang;Piao Luo;Liuhai Zheng;Jiayun Chen;Junzhe Zhang;Huan Tang;Dandan Liu;Xueling He;Qiaoli Shi;Liwei Gu;Jiahao Li;Qiuyan Guo;Chuanbin Yang;Yin Kwan Wong;Fei Xia;Jigang Wang-.18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs)[J].药物分析学报（英文）,2022(04):570-582

18beta,glycyrrhetinic,chemoproteomic

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