Tanshinone IIA alleviates liver fibrosis by suppressing hepatic stellate cell proliferation via ERK/cyclin D1/p-Smad3L signaling axis
نویسندگان
1 School of Medicine, Jianghan University, Wuhan 430056, China
2 School of Medicine, Jingchu University of Technology, Jingmen 448000, China
3 School of Medicine, Jianghan University, Wuhan 430056, China
4 School of Medicine, Jianghan University, Wuhan 430056, China
5 School of Medicine, Jianghan University, Wuhan 430056, China
6 School of Medicine, Jianghan University, Wuhan 430056, China
7 School of Medicine, Jianghan University, Wuhan 430056, China
8 School of Medicine, Jianghan University, Wuhan 430056, China
9 School of Medicine, Jianghan University, Wuhan 430056, China
10 School of Medicine, Jianghan University, Wuhan 430056, China
doi
10.22038/ijbms.2025.83092.17962چکیده
Objective(s): Liver fibrosis (LF) is a critical stage in chronic liver disease progression, and effective therapeutic drugs are currently lacking. Tanshinone IIA (Tan IIA), a monomer extracted from Salvia miltiorrhiza, shows potential in treating LF. This research aims to discuss the antifibrotic efficacy and underlying pharmacological mechanism of Tan IIA. Materials and Methods: The in vivo model was induced with CCl4 to form a LF model in mice, and the in vitro model was induced by TGF-β1 in LX-2 and HSC-T6 cells. Liver pathology was characterized by HE, Masson, and Sirius red staining, and serum levels of ALT, AST, LDH, and γ-GT were examined. Cell viability and proliferation were detected by Cell Counting Kit-8 and colony formation assays. Cell cycle distribution was detected by flow cytometry. The protein levels of p-ERK, cyclin D1, CDK4, and p-Smad3L were assessed through Western blot, immunohistochemistry, or immunofluorescence assays.Results: Tan IIA markedly decreased serum levels of ALT, AST, LDH, and γ‐GT. Collagen I and α-SMA were reduced, as shown by in vitro and in vivo models. Moreover, while arresting HSCs in the G1 phase was increased, Tan II A markedly inhibited cell viability and colony formation. Mechanistically, Tan IIA decreased the expression of p-ERK, cyclin D1, CDK4, and p-Smad3L proteins in TGF-β1-activated cells and CCl4-induced mice.Conclusion: Tan IIA may improve LF by regulating the signaling axis of ERK/cyclin D1/p-Smad3L, thereby blocking activated HSCs in the G1 phase and inhibiting their proliferation.
