Treatment strategies and prospects for hepatic fibrosis: Application of traditional Chinese medicine polysaccharides in modulating of the TGF-β1/Smad pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatic fibrosis (HF) is a common pathological feature of chronic liver disease, which can progress to cirrhosis and hepatocellular carcinoma. Conventional drugs typically target a single gene or protein, which may limit their efficacy against the complex, multifactorial nature of HF. Transforming growth factor-β1 (TGF-β1) and its downstream Smad signaling pathway play a central role in HF pathogenesis. Traditional Chinese medicine (TCM) polysaccharides, characterized by structural diversity and multi-target actions, have been shown to effectively modulate the TGF-β1/Smad pathway among other targets. Consequently, they offer a distinct advantage over single-molecule drugs and represent a promising therapeutic strategy for targeted intervention in HF.

AIM OF THE STUDY: This review synthesizes the latest advances in TCM polysaccharides in the field of HF, focusing on their application in treating HF through targeting the TGF-β1/Smad pathway, and summarizes the intervention strategies of TCM polysaccharides in HF.

MATERIALS AND

METHODS

Through searches of databases such as PubMed, Web of Science, and ScienceDirect, relevant studies were systematically retrieved. The retrieval time range was from the establishment of the databases to January 2026. The search keywords adopted include "HF", "TCM polysaccharides", "TGF-β1/Smad pathway" and "targeted delivery", as well as their keyword combinations. By comprehensively analyzing the data from dozens of in vivo and in vitro experimental studies published in recent years, the mechanism of action is evaluated.

RESULTS

Currently, therapeutic agents for HF mainly focus on regulating lipid metabolism, inflammatory responses and abnormal cell death. The transforming growth factor-β1/Smad pathway represents a key pathogenic mechanism in HF. Smad2 and Smad3 are two major downstream regulatory factors promoting TGF-β1-mediated tissue fibrosis, while Smad7 is a negative feedback regulatory factor of the TGF-β1/Smad pathway, inhibiting TGF-β1-mediated HF. Its specific anti-fibrotic mechanisms are closely associated with suppressing hepatic inflammation, inhibiting hepatic stellate cell (HSC) activation and proliferation, regulating the synthesis and secretion of pro-fibrotic factors, and modulating extracellular matrix (ECM) synthesis and degradation.

CONCLUSIONS

This review primarily focuses on the molecular regulatory mechanisms of the TGF-β1/Smad signaling pathway in HF. It also summarizes TCM polysaccharides that target and modulate the TGF-β1/Smad pathway, aiming to provide reference and insights for the treatment of HF.