Research progress in signal pathways of traditional Chinese medicine in anti-liver fibrosis

doi:10.19803/j.1672-8629.20260072

Abstract

Abstract: Objective To investigate the multi-target and multi-pathway intervention mechanisms of traditional Chinese medicine (TCM) monomers and compound formulas in the treatment of hepatic fibrosis in order to provide data for efforts to overcome the limitations of single-target Western medicine therapy. Methods Research papers on TCM against hepatic fibrosis published in recent years were retrieved and reviewed. The main signaling pathway networks with interventions by TCM (including TGF-β/Smad, PI3K/Akt, NOX4/ROS, MAPK, JAK/STAT3, NF-κB, Notch, Wnt/β-Catenin, etc.) were summarized. The characteristics and molecular mechanisms of “multi-target, multi-pathway, and multi-link” synergistic regulation were analyzed. Results TCM could simultaneously intervene in key signaling networks of hepatic fibrosis via multiple therapeutic effects, such as inhibition of hepatic stellate cell (HSC) activation, blockade of collagen deposition, promotion of matrix degradation, and induction of HSC apoptosis, which gave TCM advantages in reversing early-stage fibrosis. Conclusion More research should be devoted to the precise identification of active components and target validation of TCM against hepatic fibrosis while compatibility strategies are to be optimized based on modern omics technologies and network pharmacology so as to contribute to precise prevention and treatment of hepatic fibrosis.

Key words: Liver Fibrosis, Traditional Chinese Medicine, Signaling Pathway, Hepatic Stellate Cell, Signal Transduction

CLC Number:

Zhang Chenlu, Li Mingqi, Wang Yinghe, Ma Yuehong. Research progress in signal pathways of traditional Chinese medicine in anti-liver fibrosis[J]. Chinese Journal of Pharmacovigilance, 2026, 23(7): 829-834.

Add to citation manager EndNote|Ris|BibTeX

URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20260072

https://zgywjj.magtechjournal.com/EN/Y2026/V23/I7/829

References

[1] Zhou Xin, Wang Zhi, He Xueru, et al.Research progress on potential anti-liver fibrosis drugs and target-related signaling pathways[J]. Journal of Clinical Hepatology(临床肝胆病杂志), 2023, 39(12): 2932-2941.
[2] Meinian Onehealth Healthcare Holdings Co., Ltd., Zhongguancun Meinian Health Industry Research Institute. Blue Book of Big Data on Health Examinations2023(美年健康2023年度健康体检大数据蓝皮书)[EB/OL]. (2024-07-06)[2025-12-16]. https://max.book118.com/
html/2024/0626/7141112031006125.shtm.
[3] Shi Meijie, Xiao Huanming, Xie Yubao, et al.Current status, challenges, and reflections on the prevention and treatment of chronic hepatitis B liver fibrosis with traditional Chinese medicine[J]. Journal of Clinical Hepatology(临床肝胆病杂志), 2023, 39(6): 1281-1286.
[4] Zhou M, Wang J, Pan J, et al.Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy[J]. Nature Communications, 2023, 14(1): 3593.
[5] Xin X, Cheng X, Zeng F, et al.The role of TGF-β/SMAD signaling in hepatocellular carcinoma: from mechanism to therapy and prognosis[J]. International Journal of Biological Sciences, 2024, 20(4): 1436.
[6] Zhu W, Cui Y, Qiu J, et al.Exploring the therapeutic potential of TGF-β inhibitors for liver fibrosis: targeting multiple signaling pathways[J]. Journal of Clinical and Translational Hepatology, 2025, 13(7): 588-598.
[7] Ghafouri-Fard S, Khanbabapour S A, Hussen B M, et al.Interplay between PI3K/AKT pathway and heart disorders[J]. Molecular Biology Reports, 2022, 49(10): 9767-9781.
[8] Gao Xiaoyang, Zhao Xiaolu, Zhang Chunyan, et al.Quercetin induces apoptosis in hepatic stellate cells by regulating miR-146 and affecting the PI3K/Akt signaling pathway[J]. Journal of Southern Medical University(南方医科大学学报), 2023, 43(10): 1725-1733.
[9] Du J J, Sun J C, Li N, et al.β-Arrestin2 deficiency attenuates oxidative stress in mouse hepatic fibrosis through modulation of NOX4[J]. Acta Pharmacologica Sinica, 2021, 42(7): 1090-1100.
[10] Hao B, Sun R, Guo X, et al.NOX4-derived ROS promotes collagen I deposition in bronchial smooth muscle cells by activating noncanonical p38MAPK/akt-mediated TGF-β signaling[J]. Oxidative Medicine and Cellular Longevity, 2021, 2021: 6668971.
[11] Zhang Chunyan, Zhao Xiaolu, Gao Xiaoyang, et al.Anti-liver fibrosis effect of Mongolian medicine Qiwei Qinggan powder based on NF-κB signaling pathway[J]. Chinese Journal of New Drugs and Clinical Remedies(中国新药与临床杂志), 2024, 43(4): 296-303.
[12] Guo Q, Jin Y, Chen X, et al.NF-κB in biology and targeted therapy: new insights and translational implications[J]. Signal Transduction and Targeted Therapy, 2024, 9(1): 53.
[13] Ji Shaoxiu, Zhang Hengyao, Zhang Yuan, et al.Research progress on Notch signaling pathway in liver fibrosis[J]. Chinese Journal of Comparative Medicine(中国比较医学杂志), 2024, 34(6): 113-118.
[14] Li Mingqi, Zhao Xiaolu, Gao Xiaoyang, et al.Research progress on the relationship between epithelial-mesenchymal transition and liver fibrosis[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2024, 21(4): 464-468, 472.
[15] Shimizu M, Shibuya H.GSK3β regulates a novel β-catenin degradation pathway via the GID complex in wnt signaling[J]. Genes to Cells, 2025, 30(6): e70068.
[16] Pan Xuwang, Ye Jianhong, Bao Jianfeng.Research progress on mechanisms of traditional Chinese medicine against liver fibrosis[J]. Journal of Clinical Hepatology(临床肝胆病杂志), 2025, 41(10): 1981-1987.
[17] Chen X, Wang Y, Dou X, et al.Integrative metabolomics and proteomics reveal the effect and mechanism of Zi Qi decoction on alleviating liver fibrosis[J]. Scientific Reports, 2024, 14(1): 28943.
[18] Chen Dongfang, Zheng Lihong.Research overview of traditional Chinese medicine regulating notch signaling pathway in the treatment of liver fibrosis[J]. Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases(中西医结合肝病杂志), 2025, 35(2): 261-264.
[19] Wang Z, Li Y, Wang X, et al.Precision strike strategy for liver diseases trilogy with Xiao-Chai-Hu decoction: a meta-analysis with machine learning[J]. Phytomedicine, 2025, 142: 156796.
[20] Ye Ziyu, He Xuedong, Zheng Yongjun, et al.Research progress on anti-liver fibrosis mechanism of active components from Ligustri Lucidi Fructus[J]. Chinese Traditional and Herbal Drugs(中草药), 2024, 55(4): 1389-1396.
[21] Zhou L H, Chen X.Geniposide inhibits hepatic fibrosis and hepatic stellate cell activation through blocking the TGF-β1/smad signaling pathway[J]. Acta Physiologica Sinica, 2022, 74(2): 217-224.
[22] Yuan X, Gong Z, Wang B, et al.Astragaloside inhibits hepatic fibrosis by modulation of TGF-β1/smad signaling pathway[J]. Evidence-Based Complementary and Alternative Medicine, 2018, 2018: 3231647.
[23] Yao Q Y, Xu B L, Wang J Y, et al.Inhibition by curcumin of multiple sites of the transforming growth factor-beta1 signalling pathway ameliorates the progression of liver fibrosis induced by carbon tetrachloride in rats[J]. BMC Complementary Medicine and Therapies, 2012, 12: 196.
[24] Liu T, Xu L, Wang C, et al.Alleviation of hepatic fibrosis and autophagy via inhibition of transforming growth factor-β1/smads pathway through shikonin[J]. Journal of Gastroenterology and Hepatology, 2019, 34(1): 263-276.
[25] Qiao Jingyi, Li Hanwei, Chen Jinxiang, et al.Network pharmacology analysis and experimental validation of anti-liver fibrosis effect of Mori Fructus[J]. Chinese Journal of New Drugs and Clinical Remedies(中国新药与临床杂志), 2024, 43(1): 62-69.
[26] Hu Xinxin, Xu Shengjie, Meng Xiaofan, et al.Research progress on traditional Chinese medicine monomers targeting TGF-β1/Smad signaling pathway in preventing and treating renal interstitial fibrosis[J]. Chinese Journal of Integrated Traditional and Western Nephrology(中国中西医结合肾病杂志), 2024, 25(4): 365-368.
[27] Wang Xinmeng, Xiong Wei, Zi Jiaji.Research progress on the anti-fibrotic mechanism of paeoniflorin[J]. Youjiang Medical Journal(右江医学), 2024, 52(7): 647-650.
[28] Huang B H, Guo Z W, Lyu B H, et al.A role for curcumin in preventing liver fibrosis in animals: a systematic review and meta-analysis[J]. Frontiers in Pharmacology, 2024, 15: 1501570.
[29] Huang S P, Zhang Z C, Chen Y, et al.Review of Chinese medicine intervention in PI3K/AKT pathway to regulate fibrosis[J]. Medicine, 2025, 104(28): e42957.
[30] Lin X, Wei Y, Li Y, et al.Tormentic acid ameliorates hepatic fibrosis in vivo by inhibiting glycerophospholipids metabolism and PI3K/AKT/mTOR and NF-κB pathways: based on transcriptomics and metabolomics[J]. Frontiers in Pharmacology, 2022, 13: 918579.
[31] Pan C, Li L, Li G.Artesunate inhibits anti-liver fibrosis by blocking the epithelial-mesenchymal transition and regulating the C-jun N-terminal kinase pathway[J]. Indian Journal of Pharmaceutical Sciences, 2022, 84(6): 1520-1528.
[32] Lang Z, Li Y, Lin L, et al.Hepatocyte-derived exosomal miR-146a-5p inhibits hepatic stellate cell EMT process: a crosstalk between hepatocytes and hepatic stellate cells[J]. Cell Death Discovery, 2023, 9(1): 304.
[33] Le T V, Phan-Thi H T, Huynh-Thi M X, et al. Autophagy inhibitor chloroquine downmodulates hepatic stellate cell activation and liver damage in bile-duct-ligated mice[J]. Cells, 2023, 12(7): 1025.
[34] Wang S, Qin D, Xu A, et al.Upregulation of ATG9b by propranolol promo-tes autophagic cell death of hepatic stellate cells to improve liver fibrosis[J]. Journal of Cellular and Molecular Medicine, 2024, 28(2): e18076.
[35] Yang Xing, Wang Zhen, Liu Jiangkai, et al.Research progress on curcumin against liver fibrosis based on cellular signaling pathways[J]. Chinese Traditional Patent Medicine(中成药), 2023, 45(5): 1571-1576.
[36] Wang Y, Ma Z, Peng W, et al.3,5,6,7,8,3',4'-heptamethoxyflavonoid inhibits TGF-β1-induced epithelial-mesenchymal transition by regulating oxidative stress and autophagy through MEK/ERK/PI3K/AKT/mTOR signaling pathway[J]. Scientific Reports, 2025, 15(1): 4567.
[37] Zhang Y, Hua L, Lin C, et al.Pien-Tze-Huang alleviates CCl₄-induced liver fibrosis through the inhibition of HSC autophagy and the TGF-β1/Smad2 pathway[J]. Frontiers in Pharmacology, 2022, 13: 937484.
[38] Zheng Y, Zhao T, Wang J, et al.Curcumol alleviates liver fibrosis through inducing autophagy and ferroptosis in hepatic stellate cells[J]. FASEB Journal, 2022, 36(12): e22665.
[39] Gerami H, Mozaffari-Khosravi H, Mansour A, et al.Effect of nano-curcumin supplementation on liver fibrosis in patients with NAFLD-associated fibrosis: a double-blind randomized controlled trial[J]. Scientific Reports, 2025, 15(1): 38043.