Innovative strategies for anti-fibrotic drugs discovery from traditional Chinese medicine
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摘要:
纤维化疾病使全球面临重大健康挑战，现有治疗手段疗效不足、毒副作用显著。中药凭借其丰富化学多样性及悠久临床实践积累，为抗纤维化药物研发提供了独特资源，然而其开发也面临诸多瓶颈，包括组织富集性低、靶标不明、结构优化策略不足以及成药性评价体系不完善等。本文总结近年来从中药中发现抗纤维化活性化合物最新进展，提出“基于传统方剂智能创新与转化引擎”（Smart Herbal-based Innovation and Translational Engine, SHINE）的中药源创新药研发平台，其内容包括具有组织导向特性活性成分发现、抗纤维化靶标挖掘、靶标与生源合成路径指导的骨架结构优化以及跨尺度成药性评价体系。该平台整合人工智能与高通量筛选实验技术，实现候选化合物智能筛选；运用理性设计策略优化活性化合物；搭建衔接临床前发现与临床验证转化桥梁；构建闭环反馈系统，使真实世界证据持续驱动药物精准定位与二次开发。SHINE平台构建了连接传统中药理论与现代药物研发技术的枢纽，推动经典方剂向成分明确、机制清晰、靶向富集的小分子候选药物转化。SHINE旨在通过将经验性中医药知识与先进多组学、人工智能和生物合成工程相结合，研发出具有成分明确、靶点明确、安全性强、疗效显著和组织特异性富集的原创抗纤维化新药。
Abstract:
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 tissueoriented 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 stateof-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 firstin-class anti-fibrotic therapeutics with defined targets, improved safety, and demonstrable clinical efficacy.
关键词:
传统中药;经典方剂;纤维化疾病;组织导向;药物发现;结构优化;生源合成;跨尺度验证
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This work was supported by Natural Science Foundation of Sichuan Province (No. 2025ZNSFSC0051; 2025ZNSFSC0584; 2025ZNSFSC0700; 2025ZNSFSC0938; 2024NSFSC0713; 2025NSFJQ0032) and the Innovative Chinese Medicine Preclinical G. Xin, T. Wang, Q. Zhou et al. Chinese Herbal Medicines 18 (2026) 499–514511 Research Fund of ‘‘Liqing No.2”, West China Hospital, Sichuan University (No. 161200012).
Guang Xin a,, Tao Wang a,, Qilong Zhou a, Sanyin Zhang b, Zeliang Wei a, Ke Li a, Wei Chen b, Dan Sun b, Shilin Chen b, Zhaotong Cong b,?, Wen Huang a,?. Innovative strategies for anti-fibrotic drugs discovery from traditional Chinese medicine[J]. Chinese Herbal Medicines (CHM),2026,18(3):499-514
