Tanshinone IIA alleviates liver fibrosis by suppressing hepatic stellate cell proliferation via ERK/cyclin D1/p-Smad3L signaling axis

• Published in: Iranian journal of basic medical sciences Vol. 28; no. 5; pp. 638 - 646
• Main Authors: Liao, Wenjing, Wu, Fang, Hao, Zhiyuan, Ye, Rui, Liu, Chenfei, Wu, Jinglei, Wu, Min, Zhou, Xiaoman, Sun, Mingze, Liu, Yuwei, Fang, Meng
• Format: Journal Article
• Language: English
• Published: Iran Mashhad University of Medical Sciences 01.01.2025
• Subjects: erk/cyclin d1/p-smad3l - signaling; hepatic stellate cells; liver fibrosis; Original; tanshinone iia; tgf-β1; Tanshinone IIA; Hepatic stellate cells; TGF-β1; Liver fibrosis; ERK/cyclin D1/p-Smad3L – signaling
• ISSN: 2008-3866; 2008-3874
• DOI: 10.22038/ijbms.2025.83092.17962

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 , shows potential in treating LF. This research aims to discuss the antifibrotic efficacy and underlying pharmacological mechanism of Tan IIA. The model was induced with CCl to form a LF model in mice, and the model was induced by TGF-β 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. Tan IIA markedly decreased serum levels of ALT, AST, LDH, and γ-GT. Collagen I and α-SMA were reduced, as shown by and i 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-β -activated cells and CCl -induced mice. 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.