Globally, 850 million patients with liver fibrosis are still facing the long-standing dilemma of “no effective drugs available”. The ineffectiveness of single drugs and the complex pathogenesis have long been a critical clinical pain point that restricts the treatment of liver fibrosis.
A research team led by President Haiping Hao and Professor Hong Wang from China Pharmaceutical University adopted a rigorous full-chain design of “screening-verification-mechanism-transformation” to solve this clinical problem. For the first time, the team confirmed that the combination of silybin and carvedilol can synergistically alleviate liver fibrosis by inhibiting the Wnt4/β-catenin signaling pathway.
The researchers constructed a COL1A1 luciferase reporter gene screening system and tested the combination of silybin with 397 FDA-approved drugs. The combination index (CI) of silybin and carvedilol was only 0.13, showing a strong synergistic effect. In vitro experiments on primary hepatic stellate cells (pHSCs) and human hepatic stellate cells (LX-2) verified that the combination could significantly down-regulate the expression of HSC activation markers and inhibit collagen deposition. In CCl₄-induced mouse liver fibrosis models, the 50:1 fixed dose ratio of silybin to carvedilol significantly reduced liver function indexes and collagen volume fraction, and reversed liver fibrosis in a dose-dependent manner without obvious side effects.
Mechanistic studies revealed that the combination inhibits the Wnt/β-catenin pathway by down-regulating the essential mediator Wnt4, up-regulating the pathway inhibitors Wif1 and Dkk4, and reducing the expression of β-catenin, thereby blocking HSC activation and excessive collagen deposition.
Notably, both silybin and carvedilol are clinically approved drugs with mature human pharmacokinetic and safety data, which greatly reduces the risk of clinical translation. This combination is expected to be used in the clinical treatment of liver fibrosis caused by various chronic liver diseases such as metabolic dysfunction-associated steatotic liver disease and cholestatic liver disease.
This work entitled “Combination of silybin and carvedilol synergistically alleviates liver fibrosis by inhibiting Wnt/β-catenin signaling” was published online in Targetome on 15 December 2025.

DOI: 10.48130/targetome-0025-0009