ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1665648
This article is part of the Research TopicUnraveling the Molecular Web of Inflammation and Fibrosis: Pathways, Immune Interactions, Epigenetics, and Therapeutic FrontiersView all 12 articles
Bioinformatics based exploration of the anti-liver fibrosis mechanism of Pien Tze Huang via EGFR/JAK1/STAT3 pathway
Provisionally accepted
Xiaoting Hong
Yonghua YeChunfeng LinMiaolan ZhengFan LinQing Xiong
Wei XuHuang Li*
Yuqin Zhang*Haiyin Zheng*- Fujian University of Traditional Chinese Medicine, Fuzhou, China
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Object: Liver fibrosis is a key stage in chronic liver disease, but targeted treatments are scarce. Pien Tze Huang (PZH), a traditional Chinese medicine, shows anti-fibrotic potential, though its mechanisms are not fully understood. Method: A liver fibrosis model was created in C57BL/6 mice using carbon tetrachloride (CCL4). PZH's effects were assessed via liver morphology, serum/liver biomarkers, transaminase levels, and histopathology. PZH's chemical components were identified through database and literature research. Network pharmacology, molecular docking and molecular dynamics simulation were used to investigate the underlying mechanisms, which were validated in vivo and in vitro with immunofluorescence and Western blot analyses. Results: PZH significantly attenuated hepatic transaminase disorders, reduced serum procollagen III/IV, alleviated fibrotic liver histopathology, and suppressed macrophage markers and hepatic inflammation. Through multi-database integration, 24 bioactive compounds were identified in PZH, including ginsenoside Rh2. Further investigation showed that PZH ameliorates liver fibrosis by modulating key targets, including AKT1, EGFR, and STAT3. Molecular docking analysis and This is a provisional file, not the final typeset article molecular dynamics simulation demonstrated a significantly high binding affinity between ginsenoside Rh2 and the target proteins EGFR, JAK1, and STAT3. In vitro and in vivo experiments confirmed that PZH and ginsenoside Rh2, reduced RAW264.7 inflammatory mediators, inhibited M1 polarization, and downregulated EGFR/JAK1/STAT3. Conclusion: The findings reveal that PZH ameliorates liver fibrosis by inhibiting macrophage-mediated inflammation via blockade of the EGFR/JAK1/STAT3 signaling axis, providing a mechanistic foundation for its clinical application.
Keywords: liver fibrosis, Pien Tze Huang, liver inflammation, EGFR/JAK1/STAT3 signaling pathway, Network Pharmacology
Received: 14 Jul 2025; Accepted: 06 Oct 2025.
Copyright: © 2025 Hong, Ye, Lin, Zheng, Lin, Xiong, Xu, Li, Zhang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huang Li, 2010042@fjtcm.edu.cn
Yuqin Zhang, 2016003@fjtcm.edu.cn
Haiyin Zheng, 2004024@fjtcm.edu.cn
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