Liver diseases are a global health issue caused by multiple factors. At present, the drugs used for treating liver diseases in clinical practice have the drawbacks of limited efficacy and significant side effects. Therefore, it is of great significance to search for effective hepatoprotective drugs from natural products. Sophocarpine is a quino-lizidine-based alkaloid and is one of the main active components of the Chinese medicines Sophora flavescens and Sophorae tonkinensis Radix et Rhizoma. This article systematically summarizes the possible mechanisms of sophocarpine in protecting the liver, including regulation of lipid metabolism, modulation of the immune response, anti-fibrosis, an-ti-inflammatory, anti-tumor effects, etc. Furthermore, the safety evaluation results showed that sophocarpine has certain acute toxicity, neurotoxicity, hepatotoxicity, cardiotoxicity and reproductive toxicity. Future research should focus on the dual regulatory effect of sophocarpine on efficacy and toxicity, and strengthen the development of targeted preparations to provide a theoretical basis for effective and safe hepatoprotective drugs.

1. Devarbhavi H, Asrani SK, Arab JP, et al. Global burden of liver disease: 2023 update[J]. J Hepatol, 2023, 79(2): 516-537. DOI: 10.1016/j.jhep.2023.03.017.

2. Avila MA, Dufour J, Gerbes AL, et al. Recent advances in alcohol-related liver disease (ALD): summary of a Gut round table meeting[J]. Gut, 2020, 69(4): 764-780. DOI: 10.1136/gutjnl-2019-319720.

3. Bjornsson HK, Bjornsson ES. Drug-induced liver injury: pathogenesis, epidemiology, clinical features, and practical management[J]. Eur J Intern Med, 2022, 97: 26-31. DOI: 10.1016/j.ejim.2021.10.035.

4. Zeng D, Li J, Lin S, et al. Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019[J]. J Hepatol, 2021, 75(3): 547-556. DOI: 10.1016/j.jhep.2021.04.035.

5. Kawaguchi T, Tsutsumi T, Nakano D, et al. MAFLD: renovation of clinical practice and disease awareness of fatty liver[J]. Hepatol Res, 2022, 52(5): 422-432. DOI: 10.1111/hepr.13706.

6. 田宝云, 朱燕丽, 徐帆. 基于数据挖掘的保肝药物专项点评实践[J]. 解放军药学学报, 2024, 37(5): 422-428. [Tian  BY, Zhu YL, Xu F. Mata mining-based and targeted reviews of prescriptiosn for hepatoprotective drugs[J]. Pharmaceutical Journal of Chinese People's Liberation Army, 2024, 37(5): 422-428.] DOI: 10.3969/j.issn.1008-9926.2024.05.003.

7. 刘校妃, 张美玲, 朱亚芹. 保肝药临床用药分析及药师干预对药物合理使用的影响[J]. 现代诊断与治疗, 2023, 34(13): 2016-2018. [Liu XF, Zhang ML, Zhu YQ. Analysis of clinical use of liver-protecting drugs and the impact of pharmacist intervention on rational drug use[J]. Modern Diagnosis and Treatment, 2023, 34(13): 2016-2018.] DOI: 10.13193/j.issn.1001-8174.2023.13.002.

8. 孙文学, 宁炼, 唐黎明. 山豆根保肝作用与肝毒性研究进展[J]. 中华中医药学刊, 2021, 39(10): 50-54. [Sun WX, Ning L, Tang LM. Research on hepatoprotective effect and hepatotoxicity of Shandougen[J]. Chinese Archives of Traditional Chinese Medicine, 2021, 39(10): 50-54.] DOI: 10.13193/j.issn.1673-7717.2021.10.010.

9. 颜勋, 刘成宸, 张明, 等. 槐果碱对人肠癌细胞HCT-116生长抑制作用[J]. 徐州医科大学学报, 2023, 43(5): 367-372. [Yan  X, Liu CC, Zhang M, et al. Effect of sophocarpine on the growth of human HCT 116 colon cancer cells[J]. Journal of Xuzhou Medical University, 2023, 43(5): 367-372.] DOI: 10.3969/j.issn.2096-3882.2023.05.011.

10. 付聪敏, 王敏, 徐松涛, 等. 槐果碱的镇痛、抗炎作用及其对COX-2/PGE2信号通路的影响[J]. 中国药房, 2019, 30(13): 1775-1780. [Fu CM, Wang M, Xu ST, et al. Effects of analgesic and anti-inflammatory of sophocarpine and related COX-2/PGE2 signaling pathway[J]. China Pharmacy, 2019, 30(13): 1775-1780.] DOI: 10.6039/j.issn.1001-0408.2019.13.10.

11. Lin Y, Huang D, Huang H, et al. Sophocarpine ameliorates cardiac hypertrophy through activation of autophagic responses[J]. Biosci Biotechnol Biochem, 2020, 84(10): 2054-2061. DOI: 10.1080/09168451.2020.1780111.

12. 符丹丹, 段丽娜, 柏玉举, 等. 槐果碱对肺癌A549细胞增殖凋亡的作用机制[J]. 安徽医科大学学报, 2021, 56(7): 1052-1056. [Fu DD, Duan LN, Bai YJ, et al. Sophocarpine inhibits proliferation and promotes apoptosis of lung cancer A549 cells and its mechanism[J]. Acta Universitatis Medicinalis Anhui, 2021, 56(7): 1052-1056.] DOI: 10.19405/j.cnki.issn1000-1492.2021.07.010.

13. 莫安薇, 黄琰菁, 杨生辉, 等. 槐果碱对三硝基苯磺酸诱导的小鼠结肠炎的作用及其机制[J]. 中国老年学杂志, 2020, 40(19): 4177-4180. [Mo AW, Huang YJ, Yang SH, et al. Effect of Sophocarpine on TNBS-induced colitis in mice[J]. Chinese Journal of Gerontology, 2020, 40(19): 4177-4180.] DOI: 10.3969/j.issn.1005-9202.2020.19.047.

14. 吴秋兰, 李文燕, 李佳佳, 等. 槐果碱对快速性室性心律失常的影响及其电生理调控机制[J]. 中草药, 2025, 56(3): 885-894. [Wu QL, Li WY, Li JJ, et al. Effects of sophocarpine on ventricular tachyarrhythmias and its electrophysiological regulation mechanisms[J]. Chinese Traditional and Herbal Drugs, 2025, 56(3): 885-894.] DOI: 10.7501/j.issn.0253-2670.2025.03.015.

15. Lu Z, Li M, Wang J, et al. Developmental toxicity and neurotoxicity of two matrine-type alkaloids, matrine and sophocarpine, in zebrafish (Danio rerio) embryos/larvae[J]. Reprod Toxicol, 2014, 47: 33-41. DOI: 10.1016/j.reprotox.2014.05.015.

16. Das UN. Beneficial role of bioactive lipids in the pathobiology, prevention, and management of HBV, HCV and alcoholic hepatitis, NAFLD, and liver cirrhosis: a review[J]. J Adv Res, 2019, 17: 17-29. DOI: 10.1016/j.jare.2018.12.006.

17. Ipsen DH, Lykkesfeldt J, Tveden-nyborg P. Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease[J]. Cell Mol Life Sci, 2018, 75(18): 3313-3327. DOI: 10.1007/s00018-018-2860-6.

18. Lee K, Wu P, Lin H. Pathogenesis and treatment of non-alcoholic steatohepatitis and its fibrosis[J]. Clin Mol Hepatol, 2023, 29(1): 77-98. DOI: 10.3350/cmh.2022.0237.

19. Song C, Zeng X, Chen S, et al. Sophocarpine alleviates non-alcoholic steatohepatitis in rats[J]. J Gastroenterol Hepatol, 2011, 26(4): 765-774. DOI: 10.1111/j.1440-1746.2010.06561.x.

20. Mohri S, Takahashi H, Sakai M, et al. Integration of bioassay and non-target metabolite analysis of tomato reveals that beta-carotene and lycopene activate the adiponectin signaling pathway, including AMPK phosphorylation[J]. PLoS One, 2022, 17(7): e267248. DOI: 10.1371/journal.pone.0267248.

21. Song C, Shi J, Zeng X, et al. Sophocarpine alleviates hepatocyte steatosis through activating AMPK signaling pathway[J]. Toxicol In Vitro, 2013, 27(3): 1065-1071. DOI: 10.1016/j.tiv.2013.01.020.

22. Kubes P, Jenne C. Immune responses in the liver[J]. Annu Rev Immunol, 2018, 36: 247-277. DOI: 10.1146/annurev-immunol-051116-052415.

23. 黄银秋, 周厚琴, 张璐, 等. 槐果碱对小鼠免疫性肝损伤保护作用的研究[J]. 中国医院用药评价与分析, 2017, 17(3): 297-299, 303. [Huang YQ, Zhou HQ, Zhang L, et al. Study on protection of sophicarpine on immunological liver injury in mice[J]. Evaluation and Analysis of Drug-Use in Hospitals of China, 2017, 17(3): 297-299, 303.] DOI: 10.14009/j.issn.1672-2124.2017.03.003.

24. Huang Y, Li P, Wang J, et al. Inhibition of sophocarpine on poly I: C/D-GalN-induced immunological liver injury in mice[J]. Front Pharmacol, 2016, 7: 256. DOI: 10.3389/fphar.2016.00256.

25. Savio LEB, de Andrade Mello P, Figliuolo VR, et al. CD39 limits P2X7 receptor inflammatory signaling and attenuates sepsis-induced liver injury[J]. J Hepatol, 2017, 67(4): 716-726. DOI: 10.1016/j.jhep.2017.05.021.

26. Hou N, Dai X, Lu W, et al. Sophocarpine attenuates septic liver injury through suppression of the NLRP3 inflammasome via autophagy-mediated degradation[J]. Exp Ther Med, 2020, 20(6): 249. DOI: 10.3892/etm.2020.9379.

27. Bernal W. Acute liver failure: review and update[J]. Int Anesthesiol Clin, 2017, 55(2): 92-106. DOI: 10.1097/AIA.0000000000000141.

28. Jiang Z, Meng Y, Bo L, et al. Sophocarpine attenuates LPS-induced liver injury and improves survival of mice through suppressing oxidative stress, inflammation, and apoptosis[J]. Mediators Inflamm, 2018, 2018: 5871431. DOI: 10.1155/2018/5871431.

29. Xu L, Liu P. Guidelines for diagnosis and treatment of hepatic fibrosis with integrated traditional Chinese and western medicine (2019 edition)[J]. J Integr Med, 2020, 18(3): 203-213. DOI: 10.1016/j.joim.2020.03.001.

30. Li Q, Gong T, Huang Y, et al. Role of noncoding RNAs in liver fibrosis[J]. World J Gastroenterol, 2023, 29(9): 1446-1459. DOI: 10.3748/wjg.v29.i9.1446.

31. Seki E, De Minicis S, Osterreicher CH, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis[J]. Nat Med, 2007, 13(11): 1324-1332. DOI: 10.1038/nm1663.

32. Qian H, Shi J, Fan T, et al. Sophocarpine attenuates liver fibrosis by inhibiting the TLR4 signaling pathway in rats[J]. World J Gastroenterol, 2014, 20(7): 1822-1832. DOI: 10.3748/wjg.v20.i7.1822.

33. Ahmed O, Robinson MW, O'farrelly C. Inflammatory processes in the liver: divergent roles in homeostasis and pathology[J]. Cell Mol Immunol, 2021, 18(6): 1375-1386. DOI: 10.1038/s41423-021-00639-2.

34. Koyama Y, Brenner DA. Liver inflammation and fibrosis[J]. J Clin Invest, 2017, 127(1): 55-64. DOI: 10.1172/JCI88881.

35. Sang X, Wang R, Zhang C, et al. Sophocarpine protects mice from ConA-induced hepatitis via inhibition of the IFN-Gamma/STAT1 pathway[J]. Front Pharmacol, 2017, 8: 140. DOI: 10.3389/fphar.2017.00140.

36. Tian S, Li J, Xiang J, et al. The clinical relevance and immune correlation of SLC10 family genes in liver cancer[J]. J Hepatocell Carcinoma, 2022, 9: 1415-1431. DOI: 10.2147/JHC.S392586.

37. 王庆华, 韩玮, 陈达飞, 等. 槐果碱对肝癌细胞SMMC-7721和肝细胞L-O2生长的影响[J]. 中医药导报, 2018, 24(17): 31-35, 49. [Wang QH, Han W, Chen DF, et al. The effects of sophocarpine on the survival of SMMC-7721 and LO2 cells[J]. Guiding Journal of Traditional Chinese Medicine and Pharmacy, 2018, 24(17): 31-35, 49.] DOI: 10.13862/j.cnki.cn43-1446/r.2018.17.009.

38. 王庆华, 韩玮, 陈达飞, 等. 槐果碱对肝癌细胞SMMC-7721生长与侵袭的影响及机制研究[J]. 中国中西医结合杂志, 2019, 39(1): 67-71. [Wang QH, Han W, Chen DF, et al. The role and mechanism of sophocarpine on the survival and invasion of hepatoma carcinoma cell SMMC-7721[J]. Chinese Journal of Integrated Traditional and Western Medicine, 2019, 39(1): 67-71.] DOI: 10.7661/j.cjim.20180616.029.

39. Zhang P, Wang P, Qiao C, et al. Differentiation therapy of hepatocellular carcinoma by inhibiting the activity of AKT/GSK-3beta/beta-catenin axis and TGF-beta induced EMT with sophocarpine[J]. Cancer Lett, 2016, 376(1): 95-103. DOI: 10.1016/j.canlet.2016.01.011.

40. 张宏利, 杨清娥, 韩崇选, 等. 苦参杀鼠活性成分研究[J]. 兰州大学学报（自然科学版）, 2007, 43(3): 90-95. [Zhang  HL, Yang QE, Han CX, et al. Studies on the rodent-killing active components of Sophora flavescens[J]. Journal of Lanzhou University (Natural Sciences), 2007, 43(3): 90-95.] DOI: 10.13885/j.issn.0455-2059.2007.03.019.

41. 钱利武, 戴五好, 王丽丽, 等. 槐果碱及氧化槐果碱对小鼠的急性毒性[J]. 中国实验方剂学杂志, 2012, 18(13): 256-258. [Qian LW, Dai WH, Wang LL, et al. Toxicity study on sophocarpine and oxysophocarpine in mice[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2012, 18(13): 256-258.] DOI: 10.13422/j.cnki.syfjx.2012.13.080.

42. 袁惠南, 何汉增, 赵雅灵, 等. 槐果碱对中枢神经系统的抑制作用[J]. 中药通报, 1987, 12(4): 47-49. [Yuan HN, He  HZ, Zhao YL, et al. Inhibitory effect of sophocarpine on central nervous system[J]. China Journal of Chinese Materia Medica, 1987, 12(4): 47-49.] https://www.cnki.com.cn/Article/CJFDTotal-ZGZY198704034.htm.

43. Wang R, Wang M, Wang S, et al. An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes[J]. Stem Cell Res Ther, 2019, 10(1): 20. DOI: 10.1186/s13287-018-1126-4.

44. Campos LR, Khalil SM, Souza M. The epidemiology of metabolic dysfunction-associated steatotic liver disease among pediatric patients with type 2 diabetes: systematic review and meta-analysis[J]. Eur J Pediatr, 2026, 185(2): 120. DOI: 10.1007/s00431-025-06734-0.

45. 张晓雯, 李凌宇, 尚海, 等. 苦参碱及其类似物的结构修饰研究进展[J]. 中草药, 2019, 50(23): 5892-5900. [Zhang XW, Li  LY, Shang H, et al. Advances in structural modification of matrine and its analogues[J]. Chinese Traditional and Herbal Drugs, 2019, 50(23): 5892-5900.] DOI: 10.7501/j.issn.0253-2670.2019.23.034.

46. 陈曙霞, 徐瑾, 王平全, 等. 槐果碱的人体药代动力学研究[J]. 上海第二医科大学学报, 2005, 25(11): 77-79. [Chen SX, Xu  J, Wang PQ, et al. Pharmacokinetics of sophocarpine in healthy volunteers[J]. Journal of Shanghai Jiaotong University, 2005, 25(11): 77-79.] DOI: 10.3969/j.issn.1674-8115.2005.11.022.