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Journal of Traditional Chinese Medicine >

2026 , Vol. 46 >Issue 1: 110 - 118

DOI: https://doi.org/10.19852/j.cnki.jtcm.2026.01.010

Original Articles

Network pharmacological and experimental validation of the mechanism of Chaihu Guizhi Ganjiang decoction (柴胡桂枝干姜汤) regulating T helper cell 17/regulatory T cell balance to improve autoimmune hepatitis

  • Zihao LIANG ,
  • Jie GAO ,
  • Jinyun SONG ,
  • Qin ZHENG ,
  • Hongyu ZHAO
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  • 1 Clinical Research Center, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210023, China
    2 Department of Oncology, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210023, China

Received date: 2024-10-14

  Accepted date: 2025-05-29

  Online published: 2026-01-28

Supported by

Nanjing Health Science and Technology Key Medical Science and Technology Development Program: Mechanism of Action of the Modified Si-Miao Powder with Sanguisorba Carbonisata in Regulating Microbiota and Microecology for the Treatment of Recurrent Vulvovaginal Candidiasis(ZKX22039)

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Abstract

OBJECTIVE: To elucidate the therapeutic efficacy and mechanism of action of Chaihu Guizhi Ganjiang decoction (柴胡桂枝干姜汤, CGGD) in autoimmune hepatitis.

METHODS: CGGD components and potential target genes were extracted from previously published databases. The autoimmune hepatitis (AIH)-related regulatory genes were obtained from the DisGeNET database. Intersections were taken, and enrichment analyses were performed on the extracted data. Concanavalin A (ConA)-induced AIH model mice were treated with CGGD via gavage. The results of network pharmacological analysis were experimentally validated.

RESULTS: Network pharmacology revealed 228 genes at the intersection of AIH and CGGD. Kyoto Encyclopedia of Genes and Genomes analysis revealed that CGGD primarily regulates the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway and cellular metabolism in AIH. Gene Ontology enrichment analysis revealed that CGGD modulates inflammation through transcription factor-mediated signaling pathways. As predicted, CGGD attenuated ConA-induced AIH in a dose-dependent manner by activating the PI3K/AKT signaling pathway. Histopathological assessment confirmed the protective effects of CGGD against ConA-induced AIH. Further investigation revealed that CGGD regulated the T helper cell 17 (Th17)/regulatory T cell (Treg) balance by modulating the PI3K/Akt/ nuclear factor kappa-B (NF-κB) pathway.

CONCLUSIONS: This study demonstrated the therapeutic effect of CGGD on AIH through a combination of network pharmacological prediction and experimental validation. Its mechanism of action involves PI3K/Akt/ NF-κB-mediated regulation of Th17/Treg cells.

Key words： autoimmune hepatitis; T helper cell 17; regulatory T cell; phosphoinositide 3-kinase; protein kinase B; NF-kappa B; network pharmacology; Chaihu Guizhi Ganjiang decoction

Cite this article

Zihao LIANG , Jie GAO , Jinyun SONG , Qin ZHENG , Hongyu ZHAO . Network pharmacological and experimental validation of the mechanism of Chaihu Guizhi Ganjiang decoction (柴胡桂枝干姜汤) regulating T helper cell 17/regulatory T cell balance to improve autoimmune hepatitis[J]. Journal of Traditional Chinese Medicine, 2026 , 46(1) : 110 -118 . DOI: 10.19852/j.cnki.jtcm.2026.01.010

References

1. Wu H, Lou T, Pan M, et al. Chaihu Guizhi Ganjiang decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPAR alpha-mediated lipotoxicity. J Ethnopharmacol 2024; 326: 117841.
2. Sucher E, Sucher R, Gradistanac T, Brandacher G, Schneeberger S, Berg T. Autoimmune hepatitis-immunologically triggered liver pathogenesis-diagnostic and therapeutic strategies. J Immunol Res 2019; 2019: 9437043.
3. Komori A. Recent updates on the management of autoimmune hepatitis. Clin Mol Hepatol 2021; 27: 58-69.
4. Zhang Y, Tan R, Gershwin ME, Xiong M. Autoimmune hepatitis: pathophysiology. Clin Liver Dis 2024; 28: 15-35.
5. Feng TT, Zou T, Wang X, Zhao WF, Qin AL. Clinical significance of changes in the Th17/Treg ratio in autoimmune liver disease. World J Gastroenterol 2017; 23: 3832-38.
6. Behfarjam F, Nasseri-Moghaddam S, Jadali Z. Enhanced Th17 responses in patients with autoimmune hepatitis. Middle East J Dig Dis 2019; 11: 98-103.
7. Chen H, Han Z, Fan Y, et al. CD4+ T-cell subsets in autoimmune hepatitis: a review. Hepatol Commun 2023; 7: e0269.
8. Cerbulo-Vazquez A, Hernandez-Pelaez G, Arriaga-Pizano LA, et al. Characterization of CD127(-) CD25(++) Treg from human colostrum. Am J Reprod Immunol 2018; 79: 2.
9. Zhang R, Zhao Y, Chen X, Zhuang Z, Li X, Shen E. Low-dose IL-2 therapy in autoimmune diseases: an update review. Int Rev Immunol 2024; 43: 113-7.
10. Sun SM (Tang dynasty). Qian Jin Yi Fang. Shanxi: Shanxi Science and Technology Publishing House, 2010: 806.
11. Chen GR, Xie XF, Peng C. Treatment of irritable bowel syndrome by Chinese medicine: a review. Chin J Integr Med 2023; 29: 377-84.
12. Cui L, Li C, Shang Y, et al. Chaihu Guizhi Ganjiang decoction ameliorates pancreatic fibrosis via JNK/mTOR signaling pathway. Front Pharmacol 2021; 12: 679557.
13. Li M, Zhu J, Liu X, et al. Chaihu-Guizhi-Ganjiang decoction is more efficacious in treating irritable bowel syndrome than Dicetel according to metabolomics analysis. Chin Med 2022; 17: 139.
14. Zhang P, Zhang D, Zhou W, et al. Network pharmacology: Towards the artificial intelligence-based precision Traditional Chinese Medicine. Brief Bioinform 2023; 25: 518.
15. Lai X, Wang X, Hu Y, Su S, Li W, Li S. Editorial: network pharmacology and traditional medicine. Front Pharmacol 2020; 11: 1194.
16. Li S, Zhang B. Traditional Chinese Medicine network pharmacology: theory, methodology and application. Chin J Nat Med 2013; 11: 110-20.
17. Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform 2014; 6: 13.
18. Xu HY, Zhang YQ, Liu ZM, et al. ETCM: An encyclopaedia of Traditional Chinese Medicine. Nucleic Acids Res 2019; 47: D976-82.
19. Pinero J, Sauch J, Sanz F, Furlong LI. The DisGeNET cytoscape app: exploring and visualizing disease genomics data. Comput Struct Biotechnol J 2021; 19: 2960-7.
20. Yang X, Peng WB, Yue XQ. Syndrome differentiation and treatment of Taiyang disease in Shang Han Lun. Zhong Xi Yi Jie He Xue Bao 2009; 7: 171-4.
21. Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021; 70: 1989-2003.
22. Eskandari-Nasab E, Tahmasebi A, Hashemi M. Meta-analysis: the relationship between CTLA-4 +49 A/G polymorphism and primary biliary cirrhosis and type I autoimmune hepatitis. Immunol Invest 2015; 44: 331-48.
23. Couture A, Garnier A, Docagne F, et al. HLA-class Ⅱ artificialantigen presenting cells in CD4(+) T cell-based immunotherapy. Front Immunol 2019; 10: 1081.
24. Muscate F, Woestemeier A, Gagliani N. Functional heterogeneity of CD4(+) T cells in liver inflammation. Semin Immunopathol 2021; 43: 549-61.
25. Lubbering D, Preti M, Schlott L, et al. Autoantigen-selected B cells are bystanders in spontaneous T cell-driven experimental autoimmune hepatitis. Immunology 2023; 170: 214-29.
26. Schultheiss C, Simnica D, Willscher E, et al. Next-generation immunosequencing reveals pathological T-cell architecture in autoimmune hepatitis. Hepatology 2021; 73: 1436-48.
27. Liu X, Jiang X, Liu R, et al. B cells expressing CD11b effectively inhibit CD4+ T-cell responses and ameliorate experimental autoimmune hepatitis in mice. Hepatology 2015; 62: 1563-75.
28. Christen U. Animal models of autoimmune hepatitis. Biochim Biophys Acta Mol Basis Dis 2019; 1865: 970-81.
29. Liu Y, Hao H, Hou T. Concanavalin A-induced autoimmune hepatitis model in mice: mechanisms and future outlook. Open Life Sci 2022; 17: 91-101.
30. Longhi MS, Zhang L, Mieli-Vergani G, Vergani D. B and T cells: (Still) the dominant orchestrators in autoimmune hepatitis. Autoimmun Rev 2024; 23: 103591.
31. Sirbe C, Simu G, Szabo I, Grama A, Pop TL. Pathogenesis of autoimmune hepatitis-cellular and molecular mechanisms. Int J Mol Sci 2021; 22: 13578.
32. Gao L, Zhang W, Zhang L, et al. Silencing of aryl hydrocarbon receptor repressor restrains Th 17 cell immunity in autoimmune hepatitis. J Autoimmun 2024; 143: 103162.
33. Roy T, Banang-Mbeumi S, Boateng ST, et al. Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation. Front Immunol 2022; 13: 1075804.
34. Nagai S, Kurebayashi Y, Koyasu S. Role of PI3K/Akt and mTOR complexes in Th17 cell differentiation. Ann N Y Acad Sci 2013; 1280: 30-4.
35. He C, Li Y, Gan L, et al. Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis. J Endocrinol Invest 2024; 47: 1971-86.
36. He X, Liu L, Luo X, et al. Astragalus polysaccharide relieves inflammatory responses in guinea pigs with allergic rhinitis via ameliorating NF-kB-mediated Treg/Th17 imbalance. Am J Rhinol Allergy 2022; 36: 638-48.
37. Hua Q, Zhang Y, Li H, et al. Human umbilical cord blood-derived MSCs trans-differentiate into endometrial cells and regulate Th17/Treg balance through NF-kappa B signaling in rabbit intrauterine adhesions endometrium. Stem Cell Res Ther 2022; 13: 301.
38. Noh K, Kang Y, Nepal MR, et al. Role of intestinal microbiota in baicalin-induced drug interaction and its pharmacokinetics. Molecules 2016; 21: 337.
39. Liu Z, Xiang H, Deng Q, et al. Baicalin and baicalein attenuate hyperuricemic nephropathy via inhibiting PI3K/AKT/NF-κB signalling pathway. Nephrology 2023; 28: 315-27.
40. Liu B, Piao X, Niu W, et al. Kuijieyuan decoction improved intestinal barrier injury of ulcerative colitis by affecting TLR4-dependent PI3K/AKT/NF-κB oxidative and inflammatory signaling and gut microbiota. Front Pharmacol 2020; 11: 1036.
41. Gao T, Zhang M, Li M, et al. Nuezhenoside G13 from Osmanthus fragrans fruit ameliorates Concanavalin A-induced autoimmune hepatitis by regulating the NF-κB/MAPK pathway. J Ethnopharmacol 2024; 319: 117257.
42. Zhang M, Li Q, Zhou C, Zhao Y, Li R, Zhang Y. Demethyleneberberine attenuates concanavalin A-induced autoimmune hepatitis in mice through inhibition of NF-κB and MAPK signaling. Int Immunopharmacol 2020; 80: 106137.
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