Innovative strategies for anti-fibrotic drugs discovery from traditional Chinese medicine

Fibrotic diseases represent a major global health burden, with current therapies often limited by modest efficacy and substantial side effects. Traditional Chinese medicine (TCM) provides a rich yet underexplored reservoir for anti-fibrotic drug discovery, valued for its chemical diversity and extensive clinical history. Nonetheless, conventional approaches to deriving therapeutics from these multi-component formulas face significant challenges, including low tissue selectivity, limited target specificity, suboptimal scaffold optimization, and incomplete cross-scale validation. Here, we summarize recent advances in discovering TCM-derived anti-fibrotic compounds and highlight emerging strategies, including tissue-oriented active compound discovery, fibrosis-target mining, scaffold optimization guided by targets and biosynthesis, and cross-scale validation. Building on these developments, we introduce the Smart Herbal-based Innovation and Translational Engine (SHINE), an intelligent discovery platform that prioritizes promising herbal candidates using modern computational and experimental methods; innovative development of optimized compounds or novel derivatives; a translational pipeline to unite preclinical findings and clinical validation; and a closed-loop feedback system where real-world evidence continuously informs drug repositioning and secondary development. SHINE bridges TCM principles with state-of-the-art drug discovery technologies, enabling the development of well-defined, mechanism-based small-molecule candidates from classical formulas. By integrating empirical herbal knowledge with advanced multi-omics, artificial intelligence, and biosynthetic engineering, SHINE aims to deliver first-in-class anti-fibrotic therapeutics with defined targets, improved safety, and demonstrable clinical efficacy.