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Liao, Wenjing, Wu, Fang, Hao, Zhiyuan, Wu, Jinglei, Liu, Chenfei, Wu, Min, Zhou, Xiaoman, Sun, Mingze, Liu, Yuwei, Fang, Meng. (1404). Tanshinone IIA alleviates liver fibrosis by suppressing hepatic stellate cell proliferation via ERK/cyclin D1/p-Smad3L signaling axis. , 28(5), 638-646. doi: 10.22038/ijbms.2025.83092.17962
Wenjing Liao; Fang Wu; Zhiyuan Hao; Jinglei Wu; Chenfei Liu; Min Wu; Xiaoman Zhou; Mingze Sun; Yuwei Liu; Meng Fang. "Tanshinone IIA alleviates liver fibrosis by suppressing hepatic stellate cell proliferation via ERK/cyclin D1/p-Smad3L signaling axis". , 28, 5, 1404, 638-646. doi: 10.22038/ijbms.2025.83092.17962
Liao, Wenjing, Wu, Fang, Hao, Zhiyuan, Wu, Jinglei, Liu, Chenfei, Wu, Min, Zhou, Xiaoman, Sun, Mingze, Liu, Yuwei, Fang, Meng. (1404). 'Tanshinone IIA alleviates liver fibrosis by suppressing hepatic stellate cell proliferation via ERK/cyclin D1/p-Smad3L signaling axis', , 28(5), pp. 638-646. doi: 10.22038/ijbms.2025.83092.17962
Liao, Wenjing, Wu, Fang, Hao, Zhiyuan, Wu, Jinglei, Liu, Chenfei, Wu, Min, Zhou, Xiaoman, Sun, Mingze, Liu, Yuwei, Fang, Meng. Tanshinone IIA alleviates liver fibrosis by suppressing hepatic stellate cell proliferation via ERK/cyclin D1/p-Smad3L signaling axis. , 1404; 28(5): 638-646. doi: 10.22038/ijbms.2025.83092.17962

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

Iranian Journal of Basic Medical Sciences
مقاله 11، دوره 28، شماره 5، مرداد 2025، صفحه 638-646    اصل مقاله (685.18 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2025.83092.17962
نویسندگان
Wenjing Liao1؛ Fang Wu1؛ Zhiyuan Hao1؛ Jinglei Wu1؛ Chenfei Liu2؛ Min Wu1؛ Xiaoman Zhou1؛ Mingze Sun1؛ Yuwei Liu* 1؛ Meng Fang* 1
1School of Medicine, Jianghan University, Wuhan 430056, China
2School of Medicine, Jingchu University of Technology, Jingmen 448000, China
چکیده
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. 
کلیدواژه‌ها
ERK/cyclin D1/p-Smad3L - signaling؛ Hepatic stellate cells؛ Liver fibrosis؛ Tanshinone IIA؛ TGF-β1
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