Sinomenine Ameliorates Liver Fibrosis by Blocking TGF ‐β/ SMAD and c‐ JUN Signaling

作者：Yichao Du, Junjie Bai, Tingting Ma, Ziming Wu, Pengru Wang, Xiaolin Zhong, Wenguang Fu, Shuixiang He · 发表于：Phytotherapy Research · 年份：2025 · DOI：10.1002/ptr.8502 · 被引用次数：8 · 研究领域：Liver physiology and pathology、Liver Disease Diagnosis and Treatment、Drug Transport and Resistance Mechanisms

ABSTRACT Liver fibrosis, a pivotal pathological feature in the progression of chronic liver injury, currently lacks effective therapies. Sinomenine (SIN), a bioactive alkaloid derived from traditional Chinese medicine, demonstrates diverse pharmacological properties. However, its therapeutic potential and mechanisms in liver fibrosis remain inadequately characterized. This study investigates the anti‐fibrotic effects of SIN and its underlying molecular mechanisms. The anti‐fibrotic efficacy of SIN was evaluated in two murine models of liver fibrosis induced by carbon tetrachloride (CCl 4 ) or bile duct ligation (BDL), along with transforming growth factor‐beta 1 (TGF‐β1)‐stimulated rat hepatic stellate cells (HSC‐T6). Serum biochemical markers, histopathological analyses (Hematoxylin–Eosin, Sirius red, and Masson's trichrome staining), immunofluorescence, and immunohistochemistry were employed to assess hepatic injury and collagen deposition. Western blotting elucidated molecular mechanisms. SIN administration significantly attenuated hepatic injury in CCl 4 ‐ or BDL‐induced mice, as evidenced by reduced transaminase levels and improved histopathological features. In both in vivo and in vitro models, SIN suppressed fibrogenesis by decreasing collagen deposition and downregulating expression of α‐smooth muscle actin (α‐SMA), matrix metalloproteinase 2 (MMP2), and collagen I. Mechanistically, SIN inhibited the TGF‐β/SMAD pathway through reduced phosphorylation of SMAD2/3 and at...