Wang B, Li Y, Wang YY, Liu WQ, Xu X, Liu MM. Echoes of ancient wisdom and synergistic strategies invigorate the fight against liver fibrosis. World J Gastroenterol 2026; 32(26): 116924 [DOI: 10.3748/wjg.116924]
Corresponding Author of This Article
Ming-Ming Liu, PhD, Associate Professor, Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 5 Dongdan Third Alley, Dongcheng District, Beijing 100005, China. mingmingliu@imc.pumc.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
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Wang B, Li Y, Wang YY, Liu WQ, Xu X, Liu MM. Echoes of ancient wisdom and synergistic strategies invigorate the fight against liver fibrosis. World J Gastroenterol 2026; 32(26): 116924 [DOI: 10.3748/wjg.116924]
Bing Wang, Yuan Li, Ying-Yu Wang, Wei-Qi Liu, Xiang Xu, Ming-Ming Liu, Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China
Bing Wang, Yuan Li, Ying-Yu Wang, Wei-Qi Liu, Xiang Xu, Ming-Ming Liu, International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
Bing Wang, Yuan Li, Ming-Ming Liu, Diabetes Research Center, Chinese Academy of Medical Sciences, Beijing 100005, China
Co-first authors: Bing Wang and Yuan Li.
Author contributions: Liu MM designed the overall concept and outline of the opinion review; Wang B and Li Y drafted the original manuscript and are the co-first authors of the manuscript; Wang YY, Liu WQ, and Xu X contributed to the literature review and revision of the manuscript; Liu MM supervised the writing process; and all authors read and approved the final manuscript.
AI contribution statement: During the preparation of the opinion review, the authors utilized Grammarly for basic grammar and spelling checks to improve the readability of the text. We confirm that no portion of the main text was generated by large language models. AI was not involved in the conceptualization of the opinion review. Furthermore, no images, figures, or tables within review were generated or modified by AI tools. After utilizing the linguistic assistance, the authors reviewed and edited the manuscript and take full and complete responsibility for the integrity and accuracy of the final review.
Supported by Beijing Municipal Natural Science Foundation of China, No. 7252093.
Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose.
Corresponding author: Ming-Ming Liu, PhD, Associate Professor, Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 5 Dongdan Third Alley, Dongcheng District, Beijing 100005, China. mingmingliu@imc.pumc.edu.cn
Received: November 27, 2025 Revised: January 23, 2026 Accepted: February 25, 2026 Published online: July 14, 2026 Processing time: 211 Days and 3.9 Hours
Abstract
The persistent clinical impasse in the development of approved antifibrotic therapies underscores the limitations of reductionist magic bullet strategies against the networks driving liver fibrosis. In this opinion review, we explore recent advances in botanical synergy, utilizing the Crocus sativus-Calculus bovis medicinal pair as a paradigmatic model to validate a systems pharmacology approach that transcends empirical tradition. Beyond the concurrent modulation of the p38 MAPK and transforming growth factor-β/Smad axes, we highlight the capacity of the combinatorial interventions to exert pleiotropic effects through microbiome crosstalk via the gut-liver axis, immunometabolic reprogramming of macrophages, and epigenetic modulation. To translate the botanical intelligence into global viable pharmaceutical assets, future research must leverage artificial intelligence and spatial multi-omics to decode these dynamic pharmacological networks. Furthermore, we argue that development should pivot from static chemical standardization to bioactivity-linked quality markers to ensure bioequivalence, particularly when artificial substitutes are utilized. Successful clinical translation also demands a strategic evolution toward precision medicine, integrating real-world evidence, stratification biomarkers, and noninvasive surrogate endpoints to identify patient endotypes. Ultimately, this opinion review serves as a prototype for network medicine, suggesting that fusing the combined logic of ancient pharmacopeia with the precision of modern molecular biology constitutes a transformative blueprint for conquering multifactorial diseases.
Core Tip: The failure of reductionist magic bullet therapies in liver fibrosis necessitates a shift toward systems pharmacology and network regulation. Serving as a prime example of this paradigm, the Crocus sativus-Calculus bovis pair validates combinatorial strategies that simultaneously modulate the p38 MAPK and transforming growth factor-β/Smad axes to collapse the fibrogenic network. Clinical success depends on evolving from chemical standardization to bioactivity-linked quality control and adopting precision medicine to stratify patient endotypes.
