18beta-glycyrrhetinic acid induces ROS-mediated apoptosis to ameliorate hepatic fibrosis by targeting PRDX1/2 in activated HSCs
- Author:
Zhang QIAN
1
,
2
;
Luo PIAO
;
Zheng LIUHAI
;
Chen JIAYUN
;
Zhang JUNZHE
;
Tang HUAN
;
Liu DANDAN
;
He XUELING
;
Shi QIAOLI
;
Gu LIWEI
;
Li JIAHAO
;
Guo QIUYAN
;
Yang CHUANBIN
;
Wong Kwan YIN
;
Xia FEI
;
Wang JIGANG
Author Information
1. Artemisinin Research Center and Institute of Chinese Materia Medica,Chinese Academy of Chinese Medical Sciences,Beijing,100700,China
2. Department of Geriatrics,Shenzhen People's Hospital(The Second Clinical Medical College,Jinan University),Shenzhen,518020,China
- Keywords:
Glycyrrhetinic acid;
Hepatic fibrosis;
Peroxiredoxin;
Reactive oxygen species;
Apoptosis
- From:
Journal of Pharmaceutical Analysis
2022;12(4):570-582
- CountryChina
- Language:Chinese
-
Abstract:
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.
