基于中药系统毒理学数据库的中药致肾毒性及药物规律研究

doi:10.19803/j.1672-8629.20230346

摘要/Abstract

摘要： 目的基于中药系统毒理学数据库（TCMSTD）对中药致肾毒性及用药规律进行探究和总结。方法利用TCMSTD对收录的具有毒性的中药材按照毒性类型进行筛选并分析,总结具有肾毒性的中药材其药性、药味、功效、归经等规律。结果发现具有肾毒性的中药101种,其肾毒性依据肾脏损伤部位不同,可分为肾小管损伤、急性肾小管坏死、肾小球损伤、肾间质损伤4种,同一味中药可能对肾脏不同部位出现不同程度的损伤。具有肾毒性的中药中明确具有肾毒性的毒性成分共27种,分别属于生物碱类、酚类等13种成分类型。对肾毒性成分作用靶点进行统计分析,发现重复频次最高的靶点为ESR1、ALOX5,出现频次均为21次。101种肾毒性中药其药性多为寒、温;药味则以苦、辛为主;归经多归肝、肺、脾、肾经。结论具有肾毒性的中药药性以寒、温为主,药味以苦、辛为主,药物功效分布相对较均匀,提示一些常用传统中药在日常使用时应注意剂量与配伍,减少药物本身对肾脏的损伤。

关键词: 中药系统毒理学数据库, 肾毒性, 中药, 毒性成分, 作用机制, 减毒方法, 规律研究

Abstract: Objective To explore and summarize the nephrotoxic effects and usage of traditional Chinese medicines based on the Traditional Chinese Medicine Systems Toxicology Database(TCMSTD). Methods The TCMSTD was used to screen and analyze the toxic Chinese medicinal materials included according to their types of toxicity, and to summarize the properties, taste, efficacy, and meridian tropism of Chinese medicinal materials with nephrotoxicity. Results There were 101 types of traditional Chinese medicines that were found to cause nephrotoxicity, the nephrotoxic effects which could be divided into four types based on the locations of renal injury: renal tubular injury, acute tubular necrosis, glomerular injury and renal interstitial injury. The same traditional Chinese medicine might cause damage of varying degrees to different parts of the kidney. There were a total of 27 toxic components with renal toxicity in traditional Chinese medicines, which belonged to 13 types of components such as alkaloids and phenols. Statistical analysis of the targets of nephrotoxic components revealed that the targets with the highest repetition frequency were ESR1 and ALOX5, with a frequency of 21. One hundred and one types of nephrotoxic traditional Chinese medicines had mostly cold and warm properties. The medicinal taste was mainly bitter and spicy. The meridians were mostly attributed to the liver, lung, spleen, and kidney meridians. Conclusion The properties of traditional Chinese medicines with nephrotoxicity are mostly cold and warm, and the taste is mainly bitter and spicy. The distribution of drug efficacy is relatively uniform, indicating that TCM practitioners should pay attention to dosage and compatibility in daily use to reduce the drug-caused damage to the kidney.

Key words: Traditional Chinese Medicine Systems Toxicology Database(TCMSTD), nephrotoxicity, traditional Chinese medicine, toxic components, mechanism of action, detoxification methods, study on usage

中图分类号:

R961
R994.11

李嘉昕, 刘慧敏, 钱文秀, 马宁, 宋丽丽, 李遇伯. 基于中药系统毒理学数据库的中药致肾毒性及药物规律研究[J]. 中国药物警戒, 2024, 21(2): 173-180.

LI Jiaxin, LIU Huimin, QIAN Wenxiu, MA Ning, SONG Lili, LI Yubo. Nephrotoxic effects and usage of traditional Chinese medicines based on the Traditional Chinese Medicine Systems Toxicology Database[J]. Chinese Journal of Pharmacovigilance, 2024, 21(2): 173-180.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://www.zgywjj.com/CN/10.19803/j.1672-8629.20230346

https://www.zgywjj.com/CN/Y2024/V21/I2/173

参考文献

[1] ZHUANG YS, CAI BC, ZHANG ZL, et al.Research progress of nephrotoxicity of traditional Chinese medicine[J]. Journal of Nanjing University of Traditional Chinese Medicine(南京中医药大学学报), 2022, 38(5): 390-396.
[2] SONG L, QIAN W, YIN H, et al.TCMSTD 1.0: a systematic analysis of the traditional Chinese medicine system toxicology database[J]. Science China(Life Sciences), 2023(9): 2189-2192.
[3] National 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.
[4] Editorial Committee of “Chinese Materia Medica”by the State Administration of Traditional Chinese Medicine. Chinese Materia Medica(中华本草)[M]. Shanghai: Shanghai Science and Technology Press, 1999.
[5] XIA LY.Modern Traditional Chinese Medicine Toxicology(现代中药毒理学)[M]. Tianjin: Tianjin Science and Technology Translation and Publishing Company, 2005.
[6] ZHAO JN, YE ZG.Toxicity Theory and Safety Evaluation of Traditional Chinese Medicine(中药毒性理论与安全性评价)[M]. Beijing: People’s Health Publishing House, 2012.
[7] DU GY, FANG WX.Modern Research and Reasonable Application of Toxic Traditional Chinese Medicine (有毒中药现代研究与合理应用)[M]. Beijing: People’s Health Publishing House, 2006.
[8] SHEN PA.Adverse Reactions and Clinical Application of Traditional Chinese Medicine(中药不良反应与临床)[M]. Shanghai: Shanghai Second Military Medical University Press, 2007.
[9] MIAO MS, ZHU FP, ZHU PS.Practical Traditional Chinese Medicine Toxicology(实用中药毒理学)[M]. Shanghai: Shanghai Second Military Medical University Press, 2007.
[10] ZHANG G, MA W, XU HF.Research Progress and Application of Commonly Used Traditional Chinese Medicine Toxicity(常用中药毒性研究进展及应用)[M]. Wuhan: Hubei Science and Technology Press, 2013.
[11] SU FZ.Clinical Research on Commonly Used Toxic Traditional Chinese Medicine(常用有毒中药的临床研究)[M]. Beijing: China Medical Science Press, 2019.
[12] COTOVIO P, SILVA C, GUEDES MM, et al.Acute kidney injury by cantharidin poisoning following a silly bet on an ugly beetle[J]. Clin Kidney J, 2013, 6(2): 201-203.
[13] VERMA AK, PRASAD SB.Bioactive component, cantharidin from Mylabris cichorii and its antitumor activity against Ehrlich ascites carcinoma[J]. Cell Biol Toxicol, 2012, 28(3): 133-147.
[14] WANG C, YIN ZQ, WEI Q, et al.Histopathologic examination and ultrastructural changes of visceral organ in mice with subchronic poisoning of 1,8-cineole[J]. Chinese Journal of Veterinary Medicine(中国兽医学报), 2013, 33(10): 1584-1589.
[15] YUAN WL, HUANG ZR, XIAO SJ, et al.Acute toxicity study of flavonoids from Sophorae Tonkinensis Radix et Rhizoma on zebrafish[J]. Chinese Traditional and Herbal Drugs(中草药), 2021, 52(10): 2978-2986.
[16] GUO Q, QI Q, YOU Q, et al.Toxicological studies of gambogic acid and its potential targets in experimental animals[J]. Basic Clin Pharmacol Toxicol, 2006, 99(2): 178-184.
[17] QI Q, YOU Q, GU H, et al.Studies on the toxicity of gambogic acid in rats[J]. J Ethnopharmacol, 2008, 117(3): 433-438.
[18] YANG JP, SUN H, WANG DD, et al.MAPK signal transduction pathway involves in rhein-induced apoptosis in HK-2 Cells[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2015, 21(15): 147-151.
[19] HU YF, HUANG WY, LI YQ, et al.Mechanism of rhein on renal toxicity of mice[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2019, 25(11): 54-59.
[20] HUANG WY.Toxic mechanism of emodin based on age-related difference in the expression of mrp in liver and kidney of mouse[D]. Chengdu: Chengdu University of Traditional Chinese Medicine, 2019.
[21] HUANG WY, LI YQ, JIANG Q, et al.Apoptosis mechanism of emodin on renal toxicity in mice[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2019, 25(11): 42-47.
[22] WANG HZ.Notch1 signaling pathway and GSK-3β Study on the effect of rhubarb on nephrotoxicity induced by rhubarb[D]. Yichun: Yichun University, 2021.
[23] ZHU S, JIN J, WANG Y, et al.The endoplasmic reticulum stress response is involved in apoptosis induced by aloeemodin in HK-2 cells[J]. Food Chem Toxicol, 2012, 50(3-4): 1149-1158.
[24] LI YQ.Hepatotoxicity and nephrotoxicity mechanism of aloe-emodin based on MRP-oxidative stress in aging mice[D]. Chengdu: Chengdu University of Traditional Chinese Medicine, 2019.
[25] LI YQ, HUANG WY, LIANG YS, et al.Mechanism of nephrotoxicity of aloe emodin in mice[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2019, 25(11): 48-53.
[26] ISHII T, KUMAGAE T, WAKUI H, et al.Tissue xanthine oxidoreductase activity in a mouse model of aristolochic acid nephropathy[J]. FEBS Open Bio, 2021, 11(2): 507-518.
[27] WANG X, GIUSTI A, NY A, et al.Nephrotoxic effects in zebrafish after prolonged exposure to aristolochic acid[J]. Toxins (Basel), 2020, 12(4): 217.
[28] WANG J, HUANG K, ZHU XR, et al.Time-effect transcriptomic analysis of AAI-induced damage to renal tubular epithelial cell[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床), 2021, 37(3): 41-46.
[29] LIU X, WU J, WANG J, et al.Mitochondrial dysfunction is involved in aristolochic acid I-induced apoptosis in renal proximal tubular epithelial cells[J]. Hum Exp Toxicol, 2020, 39(5): 673-682.
[30] YEH YH, LEE YT, HSIEH HS, et al.Short-term toxicity of aristolochic acid, aristolochic acid-I and aristolochic acid-II in rats[J]. Food Chem Toxicol, 2008, 46(3): 1157-1163.
[31] ZHOU Q, YAO GT, JIN RM, et al.Study on renal cell toxicity induced by esculentoside A[J]. World Chinese Medicine(世界中医药), 2014, 9(2): 151-154.
[32] SUN XC, SONG X, GUO F, et al.Terrestrosin D, a spirostanol saponin from Tribulus terrestris L. with potential hepatorenal toxicity[J]. J Ethnopharmacol, 2022, 283: 114716.
[33] CHU LZ, WU ZB, JIA JF, et al.Pathology of toxic damage of tetrandrine to the liver, kidneys, and adrenal glands of rats[J]. Wuhan Medical Journal(武汉医学杂志), 1984(4): 258-259.
[34] WU HG, ZHANG MY, HU YY, et al.Study on the acute toxicity and effect of matrine on the blood physiological and biochemical indexes of mice[J]. China Feed(中国饲料), 2020(23):40-43.
[35] SHI FY, FENG P, SU YX, et al.Study on acute and subacute toxicity of sophoridine[J]. Progress in Veterinary Medicine(动物医学进展), 2020, 41(5): 44-50.
[36] SILICI S, DOĞAN Z, SAHIN H, et al. Acute effects of grayanotoxin in rhododendron honey on kidney functions in rats[J]. Environ Sci Pollut Res Int, 2016, 23(4): 3300-3309.
[37] PAN J, SHEN F, TIAN K, et al.Triptolide induces oxidative damage in NRK-52E cells through facilitating Nrf2 degradation by ubiquitination via the GSK-3β/Fyn pathway[J]. Toxicol In Vitro, 2019, 58: 187-194.
[38] SHEN Q, WANG J, YUAN Z, et al.Key role of organic cation transporter 2 for the nephrotoxicity effect of triptolide in rheumatoid arthritis[J]. Int Immunopharmacol, 2019, 77: 105959.
[39] JIANG F, ZHOU XR, WANG Q, et al.Cytotoxic effect and mechanism of bakuchiol and bakuchiol combined with psoralen on HK-2 cell[J]. Chinese Journal of Pharmacology and Toxicology(中国药理学与毒理学杂志), 2010, 24(1): 50-58.
[40] YAO QQ, LIU ZH, XU MC, et al.Mechanism for ginkgolic acid (15 : 1)-induced MDCK cell necrosis: mitochondria and lysosomes damages and cell cycle arrest[J]. Chin J Nat Med, 2017, 15(5): 375-383.
[41] CHEN X, CEN XB.Comparative study on the toxicity of geniposide by oral gavage in different species of animals[C]. Proceedings of the Fourth (2019) Academic Annual Meeting of the Chinese Society of Toxicology on Toxicology and Safety Evaluation of Traditional Chinese Medicine and Natural Drugs(中国毒理学会中药与天然药物毒理与安全性评价第四次, 2019: 124.
[42] TIAN J, YI Y, ZHAO Y, et al.Oral chronic toxicity study of geniposide in rats[J]. J Ethnopharmacol, 2018, 213: 166-175.
[43] ZHANG HH, WEI LG, LI HF.Effect of geniposide on subacute hepatotoxicity and nephrotoxicity in normal and jaundice rats[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2018, 24(20): 140-144.
[44] CHENG SH, ZHAO ZF, LI HF.Comparative study on dose-effect relationship about nephrotoxicity of geniposide in normal and jaundice rats[J]. Chinese Archives of Traditional Chinese(中华中医药学刊), 2018, 36(5): 1096-1098.
[45] ZHANG L, LI J, JIANG ZZ, et al.Tubular injury mechanism of aristolochic acid I and aristololactam I in rats and their effect on renal aquaporin 1 expression[J]. Traditional Chinese Drug Research and Clinical Pharmacology(中药新药与临床药理), 2011, 22(4): 359-364.
[46] ZHANG B, LI S, MEN J, et al.Long-term exposure to crotonaldehyde causes heart and kidney dysfunction through induction of inflammatory and oxidative damage in male Wistar rats[J]. Toxicol Mech Methods, 2019, 29(4): 263-275.
[47] PENG CY, LIU JQ, SHU JC, et al.Study on the protective effect of Nantianzhu seed extract on arsenic trioxide nephrotoxicity[J]. Jiangxi Journal of Traditional Chinese Medicine(江西中医药), 2014, 45(10): 27-28, 68.
[48] OFFOR SJ, MBAGWU HO, ORISAKWE OE.Lead induced hepatorenal damage in male albino rats and effects of activated charcoal[J]. Front Pharmacol, 2017, 8: 107.
[49] PENG KL, SONG MF, LIU Y, et al.Study on subacute toxicity and mutagenicity in mice caused by lead tetraoxide[J]. Industrial Health and Occupational Diseases(工业卫生与职业病), 2006(4): 205-209.
[50] ZHOU Q, JIN RM, YAO GT.Preliminary study on nephrocytes toxicity indu-ced by four traditional chinese medicine monomers in evodia rutaecarpa[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2013, 10(1): 1-5.
[51] ZHANG Q, ZHOU Q, JIN RM, et al.Preliminary study on hepatotoxicity and nephrotoxicity induced by rutaecarpine[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), 2011, 17(8): 221-225.
[52] ZHAO Y.Toxicity and compatibility with total ginsenoside study of proto-veratrine a 2. comparative long-term toxicity study of nesiritide with re-combinant human B-type natriuretic peptide on cynomolgus monkey[D]. Shanghai: Second Military Medical University, 2009.
[53] QIU M, LIU J, FENG P, et al.Cytochrome P450s regulates aloperine-induced pathological changes in mouse liver and kidney[J]. Res Vet Sci, 2020, 132: 97-100.
[54] NIE AZ, BIAN M, ZHU CS.Effects of different doses of asarum decoction on liver, kidney and lung toxicity in rats[J]. Information on Traditional Chinese Medicine(中医药信息), 2023, 40(7): 53-57.
[55] HE QQ, LIU C, QUAN W, et al.Mechanism of sophorae tonkinensis radix et rhizome-induced nephrotoxicity in rats based on network toxicology and experimental validation[J]. Chinese Pharmacological Bulletin(中国药理学通报), 2023, 39(4): 766-773.
[56] CHEN SY, MA N, XU YY, et al.Research progress on target organ toxicity and attenuation and synergistic mechanism of strychni semen[J]. Drugs & Clinic(现代药物与临床), 2023, 38(3): 725-730.
[57] WANG QX, WU CQ, LIAO MY.Toxicological studies on rhubarb and its main components[J]. Journal of Toxicology(毒理学杂志), 2007, 21(4): 301-302.
[58] LIU JW.Study on the mechanism of Asarum in pulmonary-liver-kidney toxicity based on network pharmacology and metabolomics of ¹H NMR[D]. Wuhan: Hubei University of Traditional Chinese Medicine, 2022.
[59] YI JE.Study on toxicology and its toxiciopathology of gelsemium elegans benth[D]. Changsha: Hunan Agricultural University, 2002.
[60] WU RH, BI LG, WU RH, et al.Experimental study on subacute toxicity of melia toosendan[J]. Yunnan Journal of Traditional Chinese Medicine(云南中医中药杂志), 2022, 43(9): 70-73.
[61] XIAO CH, WANG YH, LIU ML, et al.The protective effect of propofol on lipopolysaccharide-induced acute kidney injury in mice and the effect of Nrf2/HO-1/NLRP3 pathway[J]. Chinese Journal of Integrated Traditional and Western Nephrology(中国中西医结合肾病杂志), 2022, 23(7): 624-627,661.
[62] DING R, WANG KL, SHEN MD, et al.Mechanism of n-butanol position of vinegar-processed Phytolacca acinosa on reducing hepatorenal toxicity[J]. Chinese Traditional and Herbal Drugs(中草药), 2023, 54(3): 798-807.
[63] WANG SS, LU H, RONG J, et al.Pathological study on tissue injury of oxytropis kansuensis bunge in SD rats[J]. Chinese Journal of Veterinary Science(中国兽医学报), 2013, 33(2): 246-249.
[64] JIA X, FU ZZ, RU QG, et al.Study on anti-inflammation, analgesia and nephrotoxicity of different doses of asarum decoction[J]. Information on Traditional Chinese Medicine(中医药信息), 2022, 39(11): 55-59.
[65] ZHANG PP, WU Q, GE XX, et al.Research progress in toxic components and toxic mechanism of Dioscorea bulbifera L.[J]. Modern Chinese Medicine(现代中医药), 2023, 43(2): 8-12.
[66] WEN XY, ZHOU PF, WEI XJ, et al.Toxic chemical components and detoxification methods of traditional Chinese medicine[J]. Journal of Traditional Chinese Veterinary Medicine(中兽医医药杂志), 2023, 42(2): 34-38.
[67] WEI JP, GAO SJ, WANG JR, et al.Metabonomic study of radix tripterygii wilfordii processed with raphani semen to reduce nephrotoxicity based on LC-MS/MS[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床), 2022, 38(4): 126-131.
[68] HE TM, ZHANG JY, LIU L,et al.Research advances of mylabris-induced hepatorenal toxicity in recent years[J]. Chinese Journal of Modern Applied Pharmacy(中国现代应用药学), 2022, 39(24): 3310-3315.
[69] HUANG KE, LI XB.Analysis of the properties of traditional Chinese medicine with nephrotoxicity[J]. Traditional Chinese Drug Research and Clinical Pharmacology(中药新药与临床药理), 1996, 7(3): 49-50.
[70] CHEN B.The kidney toxicity Chinese medicine property of a medicine and the relation of effective composition to the analysis report of kidney toxicity Chinese medicine document datum[J]. Proceeding of Clinical Medicine(临床医药实践杂志), 2008, 17(S5): 975-976.
[71] DANG LM, YIN AW, LIU SS, et al.Related research between nephrotoxicity and four properties, five tastes and channel tropism[J]. Guangdong Chemical Industry(广东化工), 2017, 44(15): 65-67.