药物联合应用对中草药相关肝损伤的影响

郑晖; 孙蓉

doi:10.12449/JCH240803

药物联合应用对中草药相关肝损伤的影响

DOI: 10.12449/JCH240803

郑晖¹,
孙蓉^{1, 2, , ,}

1.
山东大学第二医院，济南 250033
2.
山东大学高等医学研究院，济南 250012

基金项目:

国家重点研发计划 (2022YFC3502100);

高等医学研究院前沿学科发展基金 (GYY2023QY01)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：郑晖负责文章撰写；孙蓉负责拟定写作思路、指导文章撰写并最后定稿。

详细信息

通信作者:
孙蓉， sunrong@sdu.edu.cn （ORCID： 0000-0002-9717-1409）

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出版历程
- 收稿日期: 2024-07-04
- 录用日期: 2027-07-17
- 出版日期: 2024-08-25

Influence of combined drug administration on herb-induced liver injury

Hui ZHENG¹,
Rong SUN^{1, 2
, ,
,}

1.
The Second Hospital of Shandong University，Jinan 250033，China
2.
Advanced Medical Research Institute，Shandong University，Jinan 250012，China

Research funding:

National Key Research and Development Program (2022YFC3502100);

Cutting Edge Development Fund of Advanced Medical Research Institute (GYY2023QY01)

More Information

Corresponding author: SUN Rong， sunrong@sdu.edu.cn （ORCID： 0000-0002-9717-1409）

摘要

摘要: 随着中医药在全球范围内的广泛使用和临床中药物联用情况的增多，中草药相关肝损伤（HILI）和药物安全性事件频发，这给中药新药研发和中医产业发展带来了重大挑战。目前，在系统归纳总结药物联用对HILI的影响，梳理其临床特征、发生过程和互作机制，尤其是研究中西药联用后的药效动力学和药代毒理学过程等方面，仍然存在较大不足。亟需进一步构建系统整合的研究体系，特别是在靶标分子、细胞间交流、组织间串扰和体内毒性评价等方面，开展更加精准、特异和早期的研究。通过临床与基础并行的病证基础研究，提出符合中医药理论和应用规律的HILI防控策略，将为提升病证场景下的中西药物联用水平提供基础支撑和可信证据。
- 中草药 /
- 化学性与药物性肝损伤 /
- 药物疗法，联合 /
- 药物相互作用
Abstract: With the wide application of traditional Chinese medicine （TCM） globally and combined drug use in clinical practice， there have been significant increases in herb-induced liver injury （HILI） events and drug safety events， bringing great challenges to the research and development of new TCM drugs and the development of the TCM industry. At present， there are still shortcomings in systematically summarizing the effect of combined drug use on HILI and analyzing its clinical features， pathogenesis and interaction mechanism， especially the research on pharmacodynamics and pharmacotoxicology processes after the combination of TCM and Western drugs. It is urgently needed to further construct an integrated research system， especially in the aspects of target molecules， intercellular communication， tissue crosstalk， and invivo toxicity assessment. Based on the basic research combining clinical and fundamental studies， it is necessary to put forward HILI prevention and control strategies in accordance with TCM theory and application rules， which will provide fundamental support and reliable evidence for improving the level of combined use of TCM and Western drugs in the context of diseases and syndromes.
- Drugs， Chinese Herbal /
- Chemical and Drug Induced Liver Injury /
- Drug Therapy， Combination /
- Drug Interactions

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参考文献(40)

[1]	Committee on DILI Prevention and Management, Chinese Medical Biotechnology Association; Study Group of Drug-Induced Liver Disease, Chinese Medical Association for the Study of Liver Diseases. Chinese guideline for diagnosis and management of drug-induced liver injury(2023 version)[J]. Chin J Gastroenterol, 2023, 28( 7): 397- 431. DOI: 10.3760/cma.j.cn501113-20230419-00176. 中国医药生物技术协会药物性肝损伤防治技术专业委员会, 中华医学会肝病学分会药物性肝病学组. 中国药物性肝损伤诊治指南(2023年版)[J]. 胃肠病学, 2023, 28( 7): 397- 431. DOI: 10.3760/cma.j.cn501113-20230419-00176.
[2]	Branch of Hepatobiliary Diseases, China Association of Chinese Medicine, Branch of Chinese Patent Medicine, China Association of Chinese Medicine. Guideline for diagnosis and treatment of herb-induced liver injury[J]. J Clin Hepatol, 2016, 32( 5): 835- 843. DOI: 10.3969/j.issn.1001-5256.2016.05.003. 中华中医药学会肝胆病分会, 中华中医药学会中成药分会. 中草药相关肝损伤临床诊疗指南[J]. 临床肝胆病杂志, 2016, 32( 5): 835- 843. DOI: 10.3969/j.issn.1001-5256.2016.05.003.
[3]	SHEN T, LIU YX, SHANG J, et al. Incidence and etiology of drug-induced liver injury in mainland China[J]. Gastroenterology, 2019, 156( 8): 2230- 2241. e 11. DOI: 10.1053/j.gastro.2019.02.002.
[4]	YANG Y, GE FL, TANG JF, et al. A review of herb-induced liver injury in mainland China[J]. Front Pharmacol, 2022, 13: 813073. DOI: 10.3389/fphar.2022.813073.
[5]	ZHU CW, WANG HN, YUAN JL, et al. Clinical features of drug-induced liver injury: An analysis of 445 cases[J]. J Clin Hepatol, 2018, 34( 2): 354- 358. DOI: 10.3969/j.issn.1001-5256.2018.02.027. 朱春雾, 王海南, 袁继丽, 等. 445例药物性肝损伤的临床分析[J]. 临床肝胆病杂志, 2018, 34( 2): 354- 358. DOI: 10.3969/j.issn.1001-5256.2018.02.027.
[6]	ZHAO X, CAI TT, GUO X, et al. Chronic toxicity of salt Psoralea corylifolia L. aqueous extract in male and female rats[J]. Chin J Pharmacovigil, 2021, 18( 5): 438- 443. DOI: 10.19803/j.1672-8629.2021.05.08. 赵潇, 蔡涛涛, 郭欣, 等. 盐补骨脂水提物对不同性别大鼠的长期毒性研究[J]. 中国药物警戒, 2021, 18( 5): 438- 443. DOI: 10.19803/j.1672-8629.2021.05.08.
[7]	ZHAO XM, LI XY, SUN R, et al. Study on acute toxicity of different processed ethanol extract of polygoni multiflori in mice[J]. Chin J Pharmacovigil, 2017, 14( 10): 603- 606, 610. DOI: 10.3969/j.issn.1672-8629.2017.10.007. 赵新妹, 李晓宇, 孙蓉, 等. 何首乌不同炮制品醇提物对小鼠急性毒性实验比较研究[J]. 中国药物警戒, 2017, 14( 10): 603- 606, 610. DOI: 10.3969/j.issn.1672-8629.2017.10.007.
[8]	CAI TT, HUANG NN, WANG L, et al. Experimental comparison study on acute toxicity of different processing methods of psoraleae fructus on normal mice[J]. Chin J Pharmacovigil, 2017, 14( 12): 730- 736. 蔡涛涛, 黄娜娜, 王亮, 等. 补骨脂不同炮制方式对正常小鼠急性毒性实验比较研究[J]. 中国药物警戒, 2017, 14( 12): 730- 736.
[9]	LYU DX, ZHANG F, QIN JQ, et al. Current status and advance of diagnosis of herb-induced liver injury[J]. Chin Tradit Herb Drugs, 2024, 55( 5): 1761- 1769. 吕东霞, 张帆, 秦佳琪, 等. 中草药相关肝损伤诊断的现状与进展[J]. 中草药, 2024, 55( 5): 1761- 1769.
[10]	CHALASANI NP, MADDUR H, RUSSO MW, et al. ACG clinical guideline: Diagnosis and management of idiosyncratic drug-induced liver injury[J]. Am J Gastroenterol, 2021, 116( 5): 878- 898. DOI: 10.14309/ajg.0000000000001259.
[11]	DEVARBHAVI H, AITHAL G, TREEPRASERTSUK S, et al. Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines[J]. Hepatol Int, 2021, 15( 2): 258- 282. DOI: 10.1007/s12072-021-10144-3.
[12]	LI M, LI RR, LIU CH. Clinic diagnosis and treatment of herb-induced liver injury[J]. Chin J Pharmacovigil, 2023, 20( 2): 127- 131. DOI: 10.19803/j.1672-8629.20220661. 李盟, 李容容, 刘成海. 中草药引起肝损伤的临床诊治与用药[J]. 中国药物警戒, 2023, 20( 2): 127- 131. DOI: 10.19803/j.1672-8629.20220661.
[13]	LIN LF, LI H, LIN HM, et al. A new perspective on liver injury by traditional Chinese herbs such as Polygonum multiflorum: The geographical area of harvest as an important contributory factor[J]. Front Pharmacol, 2017, 8: 349. DOI: 10.3389/fphar.2017.00349.
[14]	CUI HR, BAI ZF, SONG HB, et al. Investigation of potential toxic factors for fleece-flower root: From perspective of processing methods evolution[J]. China J Chin Mater Med, 2016, 41( 2): 333- 339. DOI: 10.4268/cjcmm20160227. 崔鹤蓉, 柏兆方, 宋海波, 等. 从古今炮制方法演变探讨何首乌毒性的潜在影响因素[J]. 中国中药杂志, 2016, 41( 2): 333- 339. DOI: 10.4268/cjcmm20160227.
[15]	TESCHKE R. Traditional Chinese medicine induced liver injury[J]. J Clin Transl Hepatol, 2014, 2( 2): 80- 94. DOI: 10.14218/JCTH.2014.00003.
[16]	FASINU PS, BOUIC PJ, ROSENKRANZ B. An overview of the evidence and mechanisms of herb-drug interactions[J]. Front Pharmacol, 2012, 3: 69. DOI: 10.3389/fphar.2012.00069.
[17]	LI CY, HE Q, TANG JF, et al. Metabolomic study on immunological stress-mediated hepatotoxicity of Polygonum multiflorum and its processed products of nine times steaming and nine times sunning[J]. Acta Pharm Sin, 2017, 52( 7): 1069- 1076. DOI: 10.16438/j.0513-4870.2017-0314. 李春雨, 何琴, 唐进法, 等. 免疫应激介导的何首乌“九蒸九晒”炮制减毒作用及代谢组学研究[J]. 药学学报, 2017, 52( 7): 1069- 1076. DOI: 10.16438/j.0513-4870.2017-0314.
[18]	XIAO XH, BAI ZF, WANG JB, et al. Traditional Chinese Medicine(TCM) safety evaluation and pharmacovigilance[J]. Chin Sci Bull, 2021, 66( 4-5): 407- 414. DOI: 10.1360/tb-2020-1034.
[19]	QUAN NV, XUAN TD, TESCHKE R. Potential hepatotoxins found in herbal medicinal products: A systematic review[J]. Int J Mol Sci, 2020, 21( 14): 5011. DOI: 10.3390/ijms21145011.
[20]	MA YH, ZHU HY, GUO SY, et al. The transport study of Veratrum nigrum and Panax ginseng based on the theory of traditional Chinese medicine[J]. Lishizhen Med Mater Med Res, 2020, 31( 4): 809- 812. DOI: 10.3969/j.issn.1008-0805.2020.04.011. 马莹慧, 朱鹤云, 郭淑英, 等. 基于中药十八反理论的人参藜芦药对吸收转运研究[J]. 时珍国医国药, 2020, 31( 4): 809- 812. DOI: 10.3969/j.issn.1008-0805.2020.04.011.
[21]	GE FL, GUO YM, CAO JL, et al. Research progress in evaluation methods and risk factors for Chinese medicines-induced liver injury[J]. Mod Chin Med, 2019, 21( 3): 284- 290. DOI: 10.13313/j.issn.1673-4890.20180925002. 葛斐林, 郭玉明, 曹俊岭, 等. 中药药源性肝损伤评价方法及风险因素研究进展[J]. 中国现代中药, 2019, 21( 3): 284- 290. DOI: 10.13313/j.issn.1673-4890.20180925002.
[22]	MA ZT, SHI Z, XIAO XH, et al. New insights into herb-induced liver injury[J]. Antioxid Redox Signal, 2023, 38( 16-18): 1138- 1149. DOI: 10.1089/ars.2022.0134.
[23]	LUO Q, YANG T, LIU CH. Difficulties in research on drug-induced liver injury of Chinese herbal medicine[J]. Chin J Integr Tradit West Med Liver Dis, 2020, 30( 1): 17- 19, 23. DOI: 10.3969/j.issn.1005-0264.2020.01.005. 罗琼, 杨涛, 刘成海. 中草药药源性肝损伤的研究难点[J]. 中西医结合肝病杂志, 2020, 30( 1): 17- 19, 23. DOI: 10.3969/j.issn.1005-0264.2020.01.005.
[24]	JI S, HE DD, SU ZY, et al. P450 enzymes-based metabolic interactions between monarch drugs and the other constituent herbs: A strategy to explore compatibility mechanism of Sangju-Yin[J]. Phytomedicine, 2019, 58: 152866. DOI: 10.1016/j.phymed.2019.152866.
[25]	XU ZN, ZHAO YQ, CHEN SY, et al. Advantage and risk analysis on combination of traditional Chinese medicines and Western medicines[J]. Chin Tradit Herb Drugs, 2023, 54( 2): 408- 415. DOI: 10.7501/j.issn.0253-2670.2023.02.007. 徐振娜, 赵逸卿, 陈思宇, 等. 中西药联合用药的优势及风险分析[J]. 中草药, 2023, 54( 2): 408- 415. DOI: 10.7501/j.issn.0253-2670.2023.02.007.
[26]	LIU D, LIANG XC. New developments in the pharmacodynamics and pharmacokinetics of combination of Chinese medicine and Western medicine[J]. Chin J Integr Med, 2017, 23( 4): 312- 319. DOI: 10.1007/s11655-016-2271-1.
[27]	YIN JY, LI XX, LI FC, et al. Identification of the key target profiles underlying the drugs of narrow therapeutic index for treating cancer and cardiovascular disease[J]. Comput Struct Biotechnol J, 2021, 19: 2318- 2328. DOI: 10.1016/j.csbj.2021.04.035.
[28]	YAN HF. Effect analysis of combined application of Chinese and western medicine[J]. Chin Community Dr, 2016, 32( 13): 121- 122. DOI: 10.3969/j.issn.1007-614x.2016.13.74. 闫海凤. 临床中西药联合应用效果分析[J]. 中国社区医师, 2016, 32( 13): 121- 122. DOI: 10.3969/j.issn.1007-614x.2016.13.74.
[29]	KONG XY, CHEN Q, WU X, et al. The research progress of interaction between Chinese and western medicine combination[J]. J Nanjing Univ Tradit Chin Med, 2018, 34( 1): 5- 11. DOI: 10.14148/j.issn.1672-0482.2018.0005. 孔雪云, 陈琦, 吴祥, 等. 中西药联用相互作用研究进展[J]. 南京中医药大学学报, 2018, 34( 1): 5- 11. DOI: 10.14148/j.issn.1672-0482.2018.0005.
[30]	SHAIKH AS, THOMAS AB, CHITLANGE SS. Herb-drug interaction studies of herbs used in treatment of cardiovascular disorders-a narrative review of preclinical and clinical studies[J]. Phytother Res, 2020, 34( 5): 1008- 1026. DOI: 10.1002/ptr.6585.
[31]	ZUO HL, HUANG HY, LIN YC, et al. Enzyme activity of natural products on cytochrome P450[J]. Molecules, 2022, 27( 2): 515. DOI: 10.3390/molecules27020515.
[32]	GUTTMAN Y, YEDIDIA I, NUDEL A, et al. New grapefruit cultivars exhibit low cytochrome P4503A4-Inhibition activity[J]. Food Chem Toxicol, 2020, 137: 111135. DOI: 10.1016/j.fct.2020.111135.
[33]	WANG DP, WANG XH, YU XJ, et al. Pharmacokinetics of anthraquinones from medicinal plants[J]. Front Pharmacol, 2021, 12: 638993. DOI: 10.3389/fphar.2021.638993.
[34]	ELMELIEGY M, VOURVAHIS M, GUO C, et al. Effect of P-glycoprotein(P-gp) inducers on exposure of P-gp substrates: Review of clinical drug-drug interaction studies[J]. Clin Pharmacokinet, 2020, 59( 6): 699- 714. DOI: 10.1007/s40262-020-00867-1.
[35]	HAZRA S, SINGH PA. Safety aspects of herb interactions: Current understanding and future prospects[J]. Curr Drug Metab, 2024, 25( 1): 28- 53. DOI: 10.2174/0113892002289753240305062601.
[36]	NICOLUSSI S, DREWE J, BUTTERWECK V, et al. Clinical relevance of St. John’s wort drug interactions revisited[J]. Br J Pharmacol, 2020, 177( 6): 1212- 1226. DOI: 10.1111/bph.14936.
[37]	FELTRIN C, OLIVEIRA SIMÕES CM. Reviewing the mechanisms of natural product-drug interactions involving efflux transporters and metabolic enzymes[J]. Chem Biol Interact, 2019, 314: 108825. DOI: 10.1016/j.cbi.2019.108825.
[38]	ZHOU X, FU L, WANG PL, et al. Drug-herb interactions between Scutellaria baicalensis and pharmaceutical drugs: Insights from experimental studies, mechanistic actions to clinical applications[J]. Biomedecine Pharmacother, 2021, 138: 111445. DOI: 10.1016/j.biopha.2021.111445.
[39]	XIE YJ, WANG CH. Herb-drug interactions between Panax notoginseng or its biologically active compounds and therapeutic drugs: A comprehensive pharmacodynamic and pharmacokinetic review[J]. J Ethnopharmacol, 2023, 307: 116156. DOI: 10.1016/j.jep.2023.116156.
[40]	SUN R. Rational cognition and scientific evaluation strategy of adverse reactions and safety of traditional Chinese medicine[J]. Adverse Drug React J, 2016, 18( 4): 241- 242. DOI: 10.3760/cma.j.issn.1008-5734.2016.04.001. 孙蓉. 中药不良反应与安全性的合理认知与科学评价策略[J]. 药物不良反应杂志, 2016, 18( 4): 241- 242. DOI: 10.3760/cma.j.issn.1008-5734.2016.04.001.