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

OBJECTIVES

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.

MATERIALS AND METHODS

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.

RESULTS

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.

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.