2. Academic Validation
  3. Salvianolic acid C attenuates liver fibrosis and inhibites hepatic stellate cell activation by targeting FAP/TβRI/SMAD axis

Salvianolic acid C attenuates liver fibrosis and inhibites hepatic stellate cell activation by targeting FAP/TβRI/SMAD axis

  • Int Immunopharmacol. 2026 Apr 15:175:116400. doi: 10.1016/j.intimp.2026.116400.
Tao Sun 1,  Xue Zheng 2,  Liang Li 1,  Jin Chu 1,  Qiang Guo 3,  Ning Yang 1,  Xue Zhang 1,  Xiaotong Li 4,  Bowen Shi 1,  Hongbin Zhang 1,  Guodong Lü 1,  Lufeng Cheng 5,  Renyong Lin 6,  Xiaojuan Bi 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.
  • 2 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi, China.
  • 3 Department of Hepatobiliary and Hydatid Diseases, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • 4 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; College of Life Sciences and Technology, Xinjiang University, Urumqi, China.
  • 5 Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; Xinjiang key lab of Echinococcosis, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China; Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Urumqi, China. Electronic address: [email protected].
PMID: 41740338 DOI: 10.1016/j.intimp.2026.116400
Abstract

Background: Liver fibrosis remains a major clinical challenge with limited effective therapeutic options. Salvianolic acid C (SAC), a major water-soluble compound derived from Salvia miltiorrhiza, has shown anti-fibrotic activity in various disease models; however, its role and underlying mechanisms in liver fibrosis remain unclear.

Methods: A CCl4-induced mouse model was used to assess the in vivo anti-fibrotic activity of SAC. LX-2 hepatic stellate cells (HSCs) were used to investigate the underlying mechanisms in vitro. Network pharmacology, machine learning, molecular docking and molecular dynamics simulations were integrated to identify potential targets. Western blotting and immunohistochemistry were used to validated the key findings in vitro and in vivo.

Results: SAC significantly reduced Collagen deposition and alleviated hepatic injury in CCl4-induced murine models. It also inhibited the expression of Col1a1, α-SMA, and Timp1 both in vivo and in vitro. FAP was implicated as a potential target of SAC, and SAC promotes FAP degradation in HSCs, thereby reducing FAP protein levels and inhibiting HSC activation in a FAP-dependent manner. SAC treatment significantly downregulated TβRI expression and inhibited SMAD phosphorylation, and these effects were attenuated by FAP overexpression.

Conclusions: SAC attenuated liver fibrosis and inhibited HSC activation by targeting FAP to suppress the TβRI/SMAD signaling pathway. This finding underscores its potential as a therapeutic agent for liver fibrosis and provides a basis for further drug development.

Keywords

Fibroblast activation protein; Hepatic stellate cells; Liver fibrosis; Network pharmacology; Salvianolic acid C.

Figures
Products