Chemical composition and mechanism investigation of subfraction from Wuwei Zijin San guided by anti-hepatic fibrosis activity

Authors

• Yazhen Guo, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610041, China
• Zhongzhi Qi, Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu 610041, China
• Yajuan Chen, Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China
• Lijuan Nie, Medical College, Tibet University, Lhasa 850002, China
• Mingyu Luo, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610041, China
• Yuechen Guo, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610041, China
• Hui Wu, Clinical Pharmacy Center, The first Affiliated Hospital of Kunming Medical University, Kunming 650032, China
• Bengui Ye, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610041, China
• Jun He, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University, Chengdu 610041, ChinaFollow

Keywords

Extracellular Matrix Receptor Interaction; Hepatic Fibrosis; Hepatic Stellate Cells; PI3K/AKT Signaling Pathway; Tibetan Medicine Combination

Abstract

BACKGROUND  Among the spectrum of hepatopathies that pose a significant global health threat, halting the progression of hepatic fibrosis is a key therapeutic objective. Wuwei Zijin San (WWZJS) is derived from a traditional Tibetan empirical formula, yet its efficacy against hepatic fibrosis, along with the underlying mechanisms and active ingredients, remains uncertain.

PURPOSE  The aim of this study was to investigate the protective effect of WWZJS against hepatic fibrosis, explore its underlying mechanisms and material basis, and evaluate the potential of direct interactions between the biologically active ingredients and their corresponding targets.

METHODS Chemical profiling of the active subfraction WWZJS was performed via UHPLC-qTOF-MS/MS-based non-targeted analysis. Pharmacodynamic evaluation was conducted in a rat model of liver fibrosis induced by 50% CCl₄. The underlying mechanism was predicted via transcriptomics combined with detection of relevant protein expression. Molecular docking and molecular dynamic (MD) simulation were employed to evaluate the interaction between the compounds and the target.

RESULTS 30% ethanol elution product, as the active subfraction of WWZJS, can induce apoptosis in activated HSCs in vitro. In vivo, it demonstrates significant ameliorative effects on CCl₄-induced hepatic fibrosis in SD rats. Transcriptomic analysis revealed its involvement in multiple pathways, including ECM-receptor interaction and the PI3K/AKT signaling pathway. Protein expression data further suggest that it may suppress ECM deposition via this signaling cascade. Molecular docking of the four major ingredients (Bergenin, Corilagin, Gallic acid and Ellagic acid) against PI3K and AKT1 showed satisfactory binding effects. Similarly, 100 active ingredients were docked with PI3K/AKT signaling pathway-related proteins from DEGs, presenting generally favorable binding performance.

CONCLUSION  WWZJS ameliorates hepatic fibrosis by suppressing activated HSC proliferation and ECM deposition, a process potentially mediated through the ITGA8/PIK3R3/AKT signaling pathway. Consistently, in vitro results showing enhanced apoptosis of activated HSCs also reveal the potential capacity of WWZJS to eliminate activated HSCs. Investigation of the binding capacity between key pathway targets and active ingredients provides a theoretical basis for elucidating the mechanism through which the active subfraction of WWZJS ameliorates hepatic fibrosis via direct protein interactions.

Abstract Image

Recommended Citation

Guo, Yazhen; Qi, Zhongzhi; Chen, Yajuan; Nie, Lijuan; Luo, Mingyu; Guo, Yuechen; Wu, Hui; Ye, Bengui; and He, Jun (2026) "Chemical composition and mechanism investigation of subfraction from Wuwei Zijin San guided by anti-hepatic fibrosis activity," Journal of Food and Drug Analysis: Vol. 34 : Iss. 4 , Article 1.
Available at: https://doi.org/10.38212/2224-6614.3609

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