Repurposed drug combination shows promising results against liver fibrosis.

Repurposed drug combination shows promising results against liver fibrosis.

Study shows promising new therapy against liver fibrosis

The study shows that this drug combination works much more effectively together than either substance alone. It offers a realistic and potentially rapid route to a new therapy against liver fibrosis.

What is liver fibrosis?

Liver fibrosis is an insidious and widespread disease that affects hundreds of millions of people worldwide. It can develop into cirrhosis of the liver or even liver cancer. Despite decades of research, no antifibrotic agent has yet been approved for clinical use. Fibrosis occurs when chronic or repeated injury to the liver - caused by viral hepatitis, alcohol abuse, metabolic diseases, toxins or autoimmune disorders - triggers an excessive wound healing response. An important element in this process is the activation of hepatic stellate cells (HSCs), which are normally inactive but are converted into cells that produce collagen, contributing to scar formation.

The role of signaling pathways

The transition from inactive to active HSCs is controlled by multiple overlapping signaling pathways, including TGF-β, PDGF, and Wnt/β-catenin signaling. This complexity makes treating the disease difficult. Since single agents typically only target one signaling pathway, combination therapies that target multiple disease mechanisms simultaneously are emerging as promising.

Combination therapy study

A study (DOI: 10.48130/targetome-0025-0009) published in the journalTargetomeson December 15, 2025 by the team of Hong Wang and Haiping Hao at China Pharmaceutical University, shows that a clinically viable combination of silybin and carvedilol can synergistically suppress hepatic stellate cell activation and thus reverse liver fibrosis. This occurs by influencing the Wnt4/β-catenin signaling pathway and offers a promising new therapeutic strategy for a disease without approved antifibrotics.

Methods of the study

To evaluate the therapeutic potential of silybin and overcome its limited efficacy, the study combined in vitro and in vivo disease models with phenotype-based drug combination screening and mechanistic analyses. Initially, liver cell injury models were used to characterize the hepatoprotective profile of silybin. These tests showed that silybin significantly restored cell viability, reduced reactive oxygen species accumulation, and suppressed the expression of inflammatory genes without causing detectable cell toxicity.

Results and findings

However, silybin only slightly reduced key fibrogenetic markers when directly assessing its antifibrotic capacity in human and rat HSCs stimulated with TGFβ1. In experimental mice given carbon-containing substances, there were only modest improvements in serum transaminases and collagen deposition, suggesting that the benefits of silybin come primarily from indirect protective effects on the liver.

To address this limitation, researchers used a COL1A1 luciferase reporter screen of 397 FDA-approved drugs in combination with silybin and identified carvedilol as the strongest synergistic partner. This combination significantly suppressed collagen production and activation of HSCs in cultured human and rat HSCs as well as primary hepatic stellate cells, outperforming both monotherapy.

Summary of the study

The study highlights a clinically viable antifibrotic strategy based on drug repurposing and rational combination therapy. Both silybin and carvedilol are already widely used and have well-established safety profiles and are inexpensive. Their combination could therefore be quickly moved into clinical trials and address an important medical need. Beyond liver fibrosis, this work demonstrates how phenotype-based screening methods can uncover unexpected but powerful synergies between existing drugs.

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