JCNRJournal of Clinical and Nursing Research2208-36852208-3693Bio-Byword Scientific Publishing Pty. Ltd.10.26689/jcnr.v9i12.13475ArticleExploring the Mechanism of Wumei Pill in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Molecular Dockinghttps://artdesignp.com/journal/JCNR/9/12/10.26689/jcnr.v9i12.13475ShangguanXinyue,WenShuangyue,LiSilong,DongChuyu,WangRuiyun,ZhangBuyue,ZhangHe20259122025-12-31Objective: To explore the molecular mechanism and action pathways of Wumei Pill in the treatment of autoimmune hepatitis (AIH) using network pharmacology and molecular docking methods. Methods: The active components and targets of Wumei Pill, as well as AIH-related disease targets, were screened through the TCMSP, GeneCards, OMIM, and Disgenet databases. Cytoscape 3.9.1 was used to construct a series of topological networks, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) enrichment analysis. Molecular docking and visualization were performed using AutoDockTools 1.5.7 and PyMOL 2.4.0. Results: A total of 124 active components of Wumei Pill, 877 drug targets, 1130 disease targets, and 64 overlapping targets were obtained. GO enrichment analysis yielded 82 biological processes, 4 cellular components, and 19 molecular functions. KEGG pathway enrichment analysis identified 21 signaling pathways. Conclusion: Wumei Pill can act on targets such as Tumor Necrosis Factor (TNF), Caspase 3 (CASP3), C-X-C Motif Chemokine Ligand 8 (CXCL8), Nuclear Factor Kappa B Subunit 1 (NFKB1), and Transforming Growth Factor Beta 1 (TGFB1) through active components including girinimbine and (R)-tetrahydroberberine. It further regulates inflammation and apoptosis-related pathways such as tumor-related signaling pathways and Th17 cell differentiation pathway to treat AIH. This study provides a theoretical basis for in-depth research on the mechanism of Wumei Pill in the treatment of AIH and the development of therapeutic drugs.

Chen H, Zhou Y, 2023, Progress in the Diagnosis and Treatment of Autoimmune Hepatitis. Guangzhou Medical Journal, 54(6): 1–6 + 16.

Reau N, Lammert C, Weinberg E, 2024, Autoimmune Hepatitis: Current and Future Therapies. Hepatology Communications, 8(6): e0458.

Ma X, Wang Q, Xiao X, et al., 2022, Guidelines for the Diagnosis and Treatment of Autoimmune Hepatitis (2021). Journal of Clinical Hepatology, 38(1): 42–49.

Schmeltzer P, Russo M, 2018, Clinical Narrative: Autoimmune Hepatitis. American Journal of Gastroenterology, 113(7): 951–958.

Li Z, He X, Xu J, et al., 2024, Clinical Observation of Wumei Pill in the Treatment of Gastroesophageal Reflux Disease of Cold-Heat Complex Type. Hebei Journal of Traditional Chinese Medicine, 46(3): 410–414.

Wang K, Lü L, 2023, One Case of Acute Optic Neuritis Treated with Modified Wumei Pill. Chinese Journal of Ophthalmology of Traditional Chinese Medicine, 33(9): 864–866.

Sun J, Huang S, Liu T, et al., 2023, Efficacy of Wumei Pill Combined with Anti-Hp Quadruple Eradication Therapy in the Treatment of Hp-Infected Chronic Atrophic Gastritis of Cold-Heat Complex Type and Its Effects on Hp Eradication Rate and Levels of IL-1β and IL-6. Journal of Guangzhou University of Chinese Medicine, 40(8): 1916–1922.

Xu Z, Wu Y, 2022, Progress in the Clinical Application of Wumei Pill. Guide of Traditional Chinese Medicine, 28(1): 143–146.

Wu F, Chen G, Fang K, et al., 2023, Network Pharmacology Research Indicates That Wu-Mei-Wan Treats Obesity by Inhibiting Th17 Cell Differentiation and Alleviating Metabolic Inflammation. Combinatorial Chemistry and High Throughput Screening, 26(1): 30–48.

Li K, Wang Z, Wang J, 2024, Wumei Pill Improves Intestinal Mucosal Inflammatory Response and Pyroptosis in Rats with Ulcerative Colitis by Regulating NLRP3 Inflammasome. Chinese Journal of Immunology, 40(1): 97–102 + 109.

Li Z, Duan Z, Wu Q, et al., 2021, Study on the Mechanism of Kuhuang Granule in the Treatment of Autoimmune Hepatitis Based on Network Pharmacology and Molecular Docking. Beijing Medicine, 43(9): 894–898.

Reau N, Lammert C, Weinberg E, 2024, Autoimmune Hepatitis: Current and Future Therapies. Hepatology Communications, 8(6): e0458.

Zhu Y, Zhang H, 2022, Progress in Clinical Application of Wumei Pill. Journal of Practical Traditional Chinese Medicine, 38(12): 2249–2253.

Webster J, Vucic D, 2020, The Balance of TNF-Mediated Pathways Regulates Inflammatory Cell Death Signaling in Healthy and Diseased Tissues. Frontiers in Cell and Developmental Biology, 8: 365.

Ren J, Ding Y, Li S, et al., 2023, Predicting the Anti-Inflammatory Mechanism of Radix Astragali Using Network Pharmacology and Molecular Docking. Medicine, 102(35): e34945.

Pasquereau S, Kumar A, Herbeis G, 2017, Targeting TNF and TNF Receptor Pathway in HIV-1 Infection: From Immune Activation to Viral Reservoirs. Viruses, 9(4): 64.

Efe C, 2013, Drug-Induced Autoimmune Hepatitis and TNF-α Blocking Agents: Is There a Real Relationship? Autoimmunity Reviews, 12(3): 337–339.

Ma X, Zhang M, Fang G, et al., 2021, Ursolic Acid Reduces Hepatocellular Apoptosis and Alleviates Alcohol-Induced Liver Injury via Irreversible Inhibition of CASP3 In Vivo. Acta Pharmacologica Sinica, 42(7): 1101–1110.

Zhang Z, Dong Q, Guan R, et al., 2022, Berberine Hydrochloride Alleviates Liver Injury Caused by Acute Hypoxia Exposure by Inhibiting the TNF-α/Caspase-8/Caspase-3 Signaling Pathway. Chinese Journal of Cellular and Molecular Immunology, 38(1): 48–53.

Di-Iacovo N, Pieroni S, Piobbico D, et al., 2023, Liver Regeneration and Immunity: A Tale to Tell. International Journal of Molecular Sciences, 24(2): 1176.

Ha H, Debnath B, Neamati N, 2017, Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases. Theranostics, 7(6): 1543–1588.

Cartwright T, Perkins N, Wilson C, 2016, NFKB1: A Suppressor of Inflammation, Ageing and Cancer. FEBS Journal, 283(10): 1812–1822.

Elkhawaga S, Gomaa M, Elsayed M, et al., 2021, NFKB1 Promoter −94 Insertion/Deletion ATTG Polymorphism (rs28362491) Is Associated with Severity and Disease Progression of Rheumatoid Arthritis Through Interleukin-6 Levels Modulation in Egyptian Patients. Clinical Rheumatology, 40(7): 2927–2937.

Stadtlober N, Flauzino T, Santos L, et al., 2021, TGFB1 + 869 T > C (rs1800470) Variant Is Independently Associated with Susceptibility, Laboratory Activity, and TGF-β1 in Patients with Systemic Lupus Erythematosus. Autoimmunity, 54(8): 569–575.

Guo W, Zhang H, Liu L, 2022, Research Progress on Autoimmune Hepatitis-Related Hepatocellular Carcinoma. Journal of Clinical Hepatology, 38(6): 1431–1435.

Tang L, Wei R, Chen R, et al., 2022, Establishment and Validation of a Cholesterol Metabolism-Related Prognostic Signature for Hepatocellular Carcinoma. Computational and Structural Biotechnology Journal, 20: 4402–4414.

Baghy K, Tátrai P, Regős E, et al., 2016, Proteoglycans in Liver Cancer. World Journal of Gastroenterology, 22(1): 379–393.

Espinoza-Sánchez N, Göttte M, 2020, Role of Cell Surface Proteoglycans in Cancer Immunotherapy. Seminars in Cancer Biology, 62: 48–67.

Nava Lauson C, Tiberti S, Corsetto P, et al., 2023, Linoleic Acid Potentiates CD8+ T Cell Metabolic Fitness and Antitumor Immunity. Cell Metabolism, 35(4): 633–650.e9.

Lee D, Choi K, Oh J, et al., 2022, Linoleic Acid Reduces Apoptosis via NF-κB During the In Vitro Development of Induced Parthenogenic Porcine Embryos. Theriogenology, 187: 173–181.

Barnabei L, Laplantine E, Mbongo W, et al., 2021, NF-κB: At the Borders of Autoimmunity and Inflammation. Frontiers in Immunology, 12: 716469.

He G, Karin M, 2011, NF-κB and STAT3: Key Players in Liver Inflammation and Cancer. Cell Research, 21(1): 159–168.

Yasuda K, Takeuchi Y, Hirota K, 2019, The Pathogenicity of Th17 Cells in Autoimmune Diseases. Seminars in Immunopathology, 41(3): 283–297.

Zhao H, 2023, Study on All-Trans Retinoic Acid Regulating Treg/Th17 Cell Balance to Improve Autoimmune Hepatitis in Mice, thesis, Lanzhou University.

Yu Q, Tu H, Yin X, et al., 2022, Targeting Glutamine Metabolism Ameliorates Autoimmune Hepatitis via Inhibiting T Cell Activation and Differentiation. Frontiers in Immunology, 13: 880262.