甘遂毒理作用及减毒机制研究进展

doi:10.19803/j.1672-8629.20240876

摘要/Abstract

摘要： 目的总结甘遂的毒性、毒性发生机制及减毒机理的相关研究,为甘遂的合理使用和毒性控制提供参考。方法通过文献调研与数据整合,分析甘遂的毒性成分、毒理作用机制及减毒方法相关问题。结果甘遂具有显著的肾脏、肝脏、胃肠、心脏及生殖毒性,其作用机制涉及炎症反应、线粒体功能障碍等多方面。可以通过炮制、配伍等方法降低甘遂的毒性,使甘遂能够更好发挥疗效。结论甘遂的毒性研究已取得显著进展,但其具体的毒性机制及减毒方法仍需进一步探索。未来的研究应结合现代毒理学技术,深入揭示甘遂的毒性作用网络,提供的更高效、安全的减毒策略,为临床安全合理用药提供参考。

关键词: 甘遂, 毒理, 毒性, 炎症反应, 线粒体功能障碍, 减毒, 作用机制

Abstract: Objective To summarize the toxicity, mechanisms for toxicity and detoxification and recent research advancements related to KANSUI RADIX so as to provide a reference for safe applications and development. Methods Based on literature review and data integration, the toxic components, toxicological mechanisms, and detoxification methods of KANSUI RADIX were analyzed. Results KANSUI RADIX was highly toxic to the kidney, liver, gastrointestinal tract, heart and reproductive system. The mechanism of action involved inflammatory response and mitochondrial dysfunction. In addition, the toxicity of KANSUI RADIX could be reduced via processing and compatibility so that its therapeutic effects might be enhanced. Conclusion Significant progress has been made in research on the toxicity of KANSUI RADIX, but more research is needed on the exact mechanisms of toxicity and approaches to detoxification. Future studies should integrate modern toxicological techniques to elucidate the toxicity network of KANSUI RADIX and develop safer and better strategies for detoxification in order to facilitate its safe and rational applications.

Key words: KANSUI RADIX, Toxicology, Toxicity, Inflammatory Response, Mitochondrial Dysfunction, Detoxification, Mechanism of Action

中图分类号:

R961
R994.11

盖晓璨, 金鑫, 刘树民. 甘遂毒理作用及减毒机制研究进展[J]. 中国药物警戒, 2025, 22(9): 1068-1072.

GAI Xiaocan, JIN Xin, LIU Shumin. Research Progress in Toxicological Effect and Attenuation Mechanisms of KANSUI RADIX[J]. Chinese Journal of Pharmacovigilance, 2025, 22(9): 1068-1072.

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https://zgywjj.magtechjournal.com/CN/Y2025/V22/I9/1068

参考文献

[1] LUO QF, ZHANG J, LI D, et al.Clinical Efficacy and Safety of Gansui Dazao Powder in Treating Patients with Chronic Heart Failure Complicated with Pleural Effusion[J]. Beijing Journal of Traditional Chinese Medicine(北京中医药), 2025, 44(4): 445-448.
[2] ZHANG Z, XU Y, SHEN A, et al.Offline Two-Dimensional Normal-Phase×Reversed-Phase Liquid Chromatography Coupled with High-Resolution Mass Spectrometry for Comprehensive Analysis of Chemical Constituents in Euphorbia kansui[J]. Journal of Chroma-tography A, 2023, 1693: 463897.
[3] Chinese Pharmacopoeia Commission.Pharmacopoeia of the People's Republic of China, Volume I(中华人民共和国药典一部)[M]. Beijing: China Medical Science Press, 2020: 89-90.
[4] SHI KY, DING Y, YE Q, et al.Textual Research on 'Kansui' in the "Wuwei Han Dynasty Medical Slips"[J]. Journal of Gansu University of Chinese Medicine(甘肃中医药大学学报), 2024, 41(3): 84-87.
[5] ZHANG Q, ZHANG Y, ZHOU SK, et al.Toxicity Reduction of Euphorbia kansui Stir-Fried with Vinegar Based on Conversion of 3-O-(2’E,4’Z-Decadi-enoyl)-20-O-acetylingenol[J]. Molecules, 2019, 24(20): 3806.
[6] ZHANG Y.The Study on Compounds of Euphorbia Kansui Based on Toxicity Screening[D]. Guangzhou: Guangdong Pharmaceutical University, 2015.
[7] SUN YY, TONG JM, ZHANG SF.Research Progress on the Incompatibility between Gansui and Licorice[J]. Journal of Chengde Medical University(承德医学院学报), 2014, 31(4): 318-320.
[8] FENG X, LI J, LI H, et al.Bioactive C21 Steroidal Glycosides from Euphorbia Kansui Promoted HepG2 Cell Apoptosis via the Degradation of ATP1A1 and Inhibited Macrophage Polarization under Co-Cultivation[J]. Molecules, 2023, 28(6): 2830.
[9] LIU YM, REN HJ.Gansui in Treating Severe Malignant Diseases: Current Status and Future Directions[J]. Journal of Tongren University(铜仁学院学报), 2013, 15(4): 132-135.
[10] YANG X, LI B, ZHI SY, et al.Modern Research Progress of Euphorbia kansui[J]. Chinese Journal of Ethnomedicine and Ethnopharmacy(中国民族民间医药), 2023, 32(8): 75-79.
[11] YANG X, LI W.Comprehensive Analysis of the Potential Mechanism of Gansui in Blocking Non-Small Cell Lung Cancer Progression[J]. Pharm Biol, 2025, 63(1): 170-187.
[12] YUAN ZZ, WANG F, WU CH, et al.Exploring Gansui for Renal Edema Treatment[J]. Zhejiang Journal of Traditional Chinese Medicine(浙江中医杂志), 2024, 59(8): 692-693.
[13] BAI X, TAN TY.Research Progress in Reproductive and Hepatorenal Toxicological Mechanisms of Tripterygium wilfordii[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2024, 21(10): 1192-1199.
[14] SUN YY, TONG JM, ZHANG T, et al.Effect of Licorice with Euphorbia kansui on Expression of Bcl-2 and Bax in Rat Kidney and Relationship with Ratio[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床), 2014, 30(6): 90-93.
[15] WANG Q, HAN X, WANG YF, et al.Compatible Effects of Vinegar-Preparing Kansui and Radix Glycyrrhizae Preparata on Renal Function and Aldosterone in Rats[J]. Asia-Pacific Traditional Medicine(亚太传统医药), 2016, 12(15): 7-10.
[16] SUN C, QI JF, YU WH, et al.Effects of 10 Kinds of Nephrotoxic TCM on Kidney Organic Anion Transporter in Mice[J]. China Pharmacy(中国药房), 2015, 26(19): 2673-2676.
[17] TANG BW, LI JJ, WU FH, et al.Effect of Kansui Radix Combining with Glycyrrhizae Radix et Rhizoma in Rats' Kidney by Metabonomics[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2015, 21(9): 88-92.
[18] XU JJ, WANG F, ZHANG Y.A Preliminary Exploration of the Principles of Toxic Chinese Medicinals Application in Synopsis of the Golden Chamber[J]. Henan Traditional Chinese Medicine(河南中医), 2024, 44(12): 1783-1787.
[19] ZHAO C, JIA Z, LI E, et al.Hepatotoxicity Evaluation of Euphorbia kansui on Zebrafish Larvae in vivo[J]. Phytomedicine, 2019, 62: 152959.
[20] ZHANG XJ, LU T, YANG B.Study on the Mechanism of Peroxidant Damage in the Liver Induced by Traditional Chinese Medicine Euphorbia kansui[J]. Chinese Journal of Biochemical Pharmaceutics(中国生化药物杂志), 2014, 34(4): 63-65, 69.
[21] SHAO X.Study on the Gastrointestinal Toxic Component of Euphorbia kansui[D]. Nanjing: Nanjing University of Chinese Medicine, 2013.
[22] GAO L.Study on the Mechanism of Attenuation in Gastrointestinal toxicity of Euphorbia kansui after Stir-Baking with Vinegar[D]. Nanjing: Nanjing University of Chinese Medicine, 2013.
[23] HAN XY, LI BR.Efficacy of Gansui Injection in Mid-Trimester Pregnancy Termination: an Observational Study[J]. Journal of Harbin Medical University(哈尔滨医科大学学报), 1979(4): 24-29.
[24] SHEN J, TANG YP, XU YC, et al.Dosage-Toxicity-Efficacy Relationship of Kansui Radix in Malignant Pleural Effusion Models Based on Walker 256 Analysis[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2016, 41(9): 1713-1717.
[25] YUAN Q, JIA L, YANG J, et al.The Role of Macrophages in Liver Metastasis: Mechanisms and Therapeutic Prospects[J]. Front Immunol, 2025, 16: 1542197.
[26] FENG X, LI J, LI H, et al.Bioactive C21 Steroidal Glycosides from Euphorbia kansui Promoted HepG2 Cell Apoptosis via the Degradation of ATP1A1 and Inhibited Macrophage Polarization under Co-Cultivation[J]. Molecules, 2023, 28(6): 2830.
[27] YAN XJ, LI L, LI ZJ, et al.Dose-Effect Comparison of Gansui Before and After Vinegar Processing on Lymphocyte Viability and Macrophage NO Release[J]. Chinese Pharmacological Bulletin(中国药理学通报), 2011, 27(5): 629-632.
[28] GAO J, GAO L, ZHANG L, et al.3-O-(2’E,4’Z-decadienoyl)-20-O-acetylingenol Induces Apoptosis in Intestinal Epithelial Cells of Rats via Mitochondrial Pathway[J]. J Ethnopharmacol, 2015, 174: 331-338.
[29] WANG XY, WANG YJ, GUO BW, et al.13-Oxyingenol-dodecanoate Inhibits the Growth of Non-Small Cell Lung Cancer Cells by Targeting ULK1[J]. Bioorg Chem, 2024, 147: 107367.
[30] WANG Y, GU L, LI J, et al.13-oxyingenol Dodecanoate Derivatives Induce Mitophagy and Ferroptosis through Targeting TMBIM6 as Potential Anti-NSCLC Agents[J]. Eur J Med Chem, 2024, 270: 116312.
[31] CHEN J, FU C, LI CH, et al.The Historical Evolution and Research Progress on Quality Standards of Stewed Kansui Radix[J]. Drug Evaluation(药品评价), 2023, 20(6): 676-678.
[32] HOU YM, TIAN T.Challenges and Solutions in Processing Toxic Chinese Medicinal Slices[J]. Xinjiang Journal of Traditional Chinese Medicine(新疆中医药), 2021, 39(5): 55-57.
[33] ZHANG L, GAO L, LI Z, et al.Bio-Guided Isolation of the Cytotoxic Terpenoids from the Roots of Euphorbia kansui against Human Normal Cell Lines L-O2 and GES-1[J]. Int J Mol Sci, 2012, 13(9): 11247-11259.
[34] GAO L, YAN XZ, LI ZJ, et al.Gastrointestinal Toxicity Attenuation of Kansui Radix Stir-Baked with Vinegar by Reducing Oxidative Injury in Mice[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2013, 19(10): 257-260.
[35] JIANG D, KANG A, YAO W, et al.Euphorbia kansui Fry-Baked with Vinegar Modulates Gut Microbiota and Reduces Intestinal Toxicity in Rats[J]. J Ethnopharmacol, 2018, 226: 26-35.
[36] YU ZM, SHEN ZT, ZHONG XS.Research Progress on the Changes of Intestinal Flora in Acute Pancreatitis by Euphorbia kansui[J]. Lingnan Modern Clinics in Surgery(岭南现代临床外科), 2023, 23(5): 444-448.
[37] LIU HX, ZHANG YS, ZHOU SK, et al.Optimization of Parameters for Stir-Frying of Kansui Radix with Vinegar Based on Conversion of Toxic Components[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2023, 48(11): 2958-2967.
[38] YANG XX, LI WL.Metabolomic Study on Liver of Rats in Physiological State Treated with Euphorbia kansui before and after Processing[J]. Chinese Journal of Hospital Pharmacy(中国医院药学杂志), 2024, 44(3): 274-286.
[39] NING CX, SU XJ, REN XJ, et al.Diuretic Effect and Mechanism of Kansui Radix and its Prepared Products on Water-Loaded Mice through TLR4/NF-κB/NLRP3 and PI3K/Akt Signaling Pathways[J]. Chinese Traditional and Herbal Drugs(中草药), 2022, 53(13): 4007-4018.
[40] YANG YX, DING JJ, TANG BW, et al.Plasma Metabolomic Changes Induced by Vinegar-Processed Kansui Treatment[J]. Academic Journal of Naval Medical University(第二军医大学学报), 2013, 34(10): 1097-1103.
[41] ZHANG J, LUO QF, LI D, et al.Application of Gansui Dazao Powder in the Syndrome Differentiation and Treatment of Heart Failure Combined with Pleural Effusion Based on The Theory of “Benefiting Urination and Defecation for Dredging Yang Instead of Warming”[J]. Beijing Journal of Traditional Chinese Medicin(北京中医药), 2024, 43(12): 1420-1423.
[42] GAO XQ, XU JD, ZHOU SK, et al.Jujubae Fructus Alleviates Intestinal Injury Caused by Toxic Medicinals in Shizao Decoction Based on Correlation between Intestinal Flora and Host Metabolism[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2023, 48(10): 2792-2802.
[43] ZHOU SK, XU JD, GAO XQ, et al.Fructus Jujubae Cooperated with Water-Expelling Members in Shizao Decoction Alleviated Intestinal Injury and Malignant Ascites by Modulating Gut Microbiota and Metabolic Homeostasis[J]. Phytomedicine, 2024, 133: 155895.
[44] AN ZJ, ZHANG KY, ZHOU MJ, et al.Study on the Material Basis and Mechanism on Glycyrrhiza Co-Administered with Sargassum pallidum, Euphorbia pekinensis, Euphorbia kansui and Daphne genkwa Incompatibility[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2023, 20(12): 1435-1440.
[45] DUAN XJ, WANG JC, YE H, et al.The Study was Based on the Composition of Toxic Effect which was by the Compatibility of Eighteen Incompatible Medicaments of Licorice with Euphorbia and Gan sui Ban xia decoction[J]. Journal of Li-Shizhen Traditional Chinese Medicine(时珍国医国药), 2018, 29(4): 849-851.