Hepatoprotective Effect of Picroside I on Thioacetamide-Induced Hepatic Fibrosis Determined by Metabolomic and Proteomic Analyses

Abstract

Background: Picroside I, a hepatoprotectant, can reduce liver injury in humans and animals. However, its anti-fibrosis effect remains unclear. This study aims to explore the mechanism of the hepatoprotective effect of picroside I on hepatic fibrosis. Methods: Male mice (12 per group) were randomly divided into six groups: control group; model group, given thioacetamide (TAA); positive group, given TAA + S-(5′-adenosyl)-L-methionine (10 mg·kg−1); low-dose group, given TAA + picroside I (25 mg·kg−1); middle-dose group, given TAA + picroside I (50 mg·kg−1); and high-dose group, given TAA + picroside I (75 mg·kg−1). Serum biochemical indicators were detected, and histological evaluation was performed. Metabolomics and proteomic analyses were conducted using liquid-chromatography coupled with tandem mass spectrometry. Findings: Picroside I can decrease the serum alanine transaminase, aspartate transaminase, collagen type IV, N-terminal peptide of type III procollagen, laminin, and hyaluronic acid levels and reduce the fibrosis area in a dose-dependent manner. In addition, picroside I altered the metabolomic profiling in hepatic fibrosis mice, including 10 urine metabolites, 16 serum metabolites, and 8 liver metabolites. Twenty-five differentially expressed proteins were reversed in the picroside I high-dose-treated group compared with the model group. Interpretation: Our results reveal whether and how picroside I protects against TAA-induced liver fibrosis in mice. Funding: National Natural Science Foundation of China, Program of Shanghai Academic/Technology Research Leader, S&T Major Special Projects, Xinglin Talent Program of Shanghai University of Traditional Chinese Medicine. Funding Statement: This work was financially supported by National Natural Science Foundation of China (project No. 81503223), the Program of Shanghai Academic/Technology Research Leader (18XD1403700; 17XD1403500), National Science and Technology (S&T) Major Special Projects (2017ZX09309006), and Xinglin Talent Program of Shanghai University of Traditional Chinese Medicine (SHUTCM2017). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The animal experiments were approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine.