Innovative strategies for anti-fibrotic drugs discovery from traditional Chinese medicine
摘要
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 underex-plored 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 for-mulas face significant challenges,including low tissue selectivity,limited target specificity,suboptimal scaffold optimization,and incomplete cross-scale validation.Here,we summarize recent advances in dis-covering 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 prior-itizes 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 continu-ously 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.
