何首乌相关肝毒性的机制研究进展

doi:10.19803/j.1672-8629.2022.06.05

摘要/Abstract

摘要： 目的分析探讨何首乌肝毒性作用机制及肝毒性物质基础。方法通过查阅何首乌文献对肝毒性机制和争议成分相关报道进行整理、分析、归纳。结果何首乌的肝毒性具体表现在影响肝脏代谢酶的功能与表达、使胆汁代谢循环及转运蛋白的功能受阻、以及免疫应激与线粒体功能紊乱等,文献报道其可能的毒性成分为脂溶性蒽醌类、特征性二苯乙烯苷类、鞣质类和二蒽酮类化合物,推测上述物质对机体的单独或协同作用可能与肝毒性发生有关。结论何首乌肝毒性机制可能众多,相关研究可为何首乌现代研发和安全运用奠定理论基础。

关键词: 何首乌, 肝毒性, 毒性机制, 蒽醌, 二苯乙烯苷, 鞣质, 二蒽酮

Abstract: Objective To analyze the mechanism of hepatotoxicity and hepatotoxic substances of Polygonum multiflorum Thunb. Methods Reports on the mechanism of hepatotoxicity and controversial components of Polygonum multiflorum Thunb. were categorized, analyzed and summarized by consulting the literature. Results The hepatotoxicity of Polygonum multiflorum was specifically manifested in the functions and expressions of liver metabolic enzymes, the obstruction of bile metabolic circulation and functions of transporters, as well as immune stress and mitochondrial dysfunction. It was reported by literature that the possible toxic components were fat-soluble anthraquinones, characteristic distyrene glycosides, tannins and bianthrone compounds. It was speculated that the individual or synergistic effect of the above substances on the body might be related to the occurrence of hepatotoxicity. Conclusion It is possible that the hepatotoxicity of Polygonum multiflorum works via varied mechanisms. Related studies are expected to facilitate the research, development and safe applications of Polygonum multiflorum.

Key words: Polygonum multiflorum Thunb., hepatotoxicity, toxicity mechanism, anthraquinone, stilbene glycoside, ta-nnin, bianthrone

中图分类号:

R961
R969.3

李妍怡, 张玉杰, 汪祺, 马双成. 何首乌相关肝毒性的机制研究进展[J]. 中国药物警戒, 2022, 19(6): 605-609.

LI Yanyi, ZHANG Yujie, WANG Qi, MA Shuangcheng. Research progress on the mechanism of hepatotoxicity associated with Polygonum multiflorum Thunb[J]. Chinese Journal of Pharmacovigilance, 2022, 19(6): 605-609.

参考文献

[1] Chinese Pharmacopoeia Commission.People's Republic of China: Volume I, 2020 edition(中华人民共和国药典: 一部, 2020年版)[S]. Beijing: China Medical Science and Technology Press, 2020.
[2] National Medical Products Administration. The State Food and Drug Administration warned to pay attention to the risk of liver injury caused by oral Polygonum multiflorum[EB/OL]. (2014-07-16)[2022-01-25]. https://www.nmpa.gov.cn/yaopin/ypjgdt/20140716145801865.html
[3] SONG HB, DU XX, GUO XX, et al.Analysis on safety and risk factors of Polygonum multiflorum based on ancient books of traditional Chinese medicine[J]. Chinese Journal of Traditional Chinese Medicine(中国中药杂志), 2015, 40(5): 985-988.
[4] NI ZM, DAI S, CHEN RS, et al.Summary of Materia Medica(本草汇言)[M]. Shanghai : Shanghai Science and Technology Press, 2005.
[5] CHEN NZ, LIU YJ.Shen Nong's Reading of Materia Medica(神农本草经读)[M]. Beijing: China Medical Science and Technology Press, 2011.
[6] LU YT, LV ZL.Lenglu medical talk--rare medical books series
(冷庐医话——珍本医籍丛刊)[M]. Beijing: TCM Ancient Books Publi-shing House, 1999.
[7] LIU ZQ, ZHAO GY.A case of Polygonum multiflorum overdose poisoning[J]. Journal of Physician Training(医师进修杂志), 1988 (3): 31.
[8] CARDENAS A, RESTREPO JC, SIERRA F, et al.Acute hepatitis due to shen-min: a herbal product derived from Polygonum multiflorum[J]. Journal of Clinical Gastroenterology, 2006, 40(7): 629-32.
[9] Drug Evaluation Center of State Food and Drug Administration. UK MHRA warns of adverse reactions of liver damage caused by Polygonum multiflorum[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2006, 3(5): 313-314.
[10] Center for Drug Reevaluation. Notice of the general office of the State Food and Drug Administration on strengthening the supervision of health food containing Polygonum multiflorum[EB/OL].(2014-07-17)[2022-01-06]. https://www.cdr-adr.org.cn/tzgg_home/201407/t20140717_39783.html.
[11] LIAN X, KE TT, HU AR.Clinical analysis of 52 cases of drug-induced liver injury caused by Polygonum multiflorum and its prepa-rations[J]. Chinese Journal of Traditional Chinese Medicine(中华中医药学刊), 2013, 31(5): 1133-1134.
[12] LIN LF.Study on liver injury components and mechanism of Polygonum multiflorum[D]. Beijing: Beijing University of Traditional Chinese Medicine, 2016.
[13] MA ZJ.Preliminary study on objectivity, clinical markers and injury mechanism of Polygonum multiflorum hepatotoxicity[D]. Chengdu: Chengdu University of Traditional Chinese Medicine, 2013.
[14] LI HY, YANG JB, LI WF, et al.In vivo hepatotoxicity screening of different extracts, components, and constituents of Polygoni multiflori Thunb. in zebrafish (Danio rerio) larvae[J]. Biomedicine & Pharmacotherapy, 2020, 131: 110524.
[15] ZHOU ZQ, WEI EW.Research progress in the establishment of animal liver injury model[J]. Journal of Jilin Institute of Chemical Technology(吉林化工学院学报), 2018, 35(11): 14-17.
[16] JIANG Y, YANG HM.Effect of tonifying kidney, removing phlegm and removing blood stasis on oxidative stress in apolipoprotein E gene knockout mice[J]. Global Traditional Chinese Medicine(环球中医药), 2014, 7(5): 321-327.
[17] LI RH, LIU J, SUN XE, et al.Research Progress on in vitro cell model for evaluation of drug hepatotoxicity[J]. Life Science Instruments(生命科学仪器), 2020, 18(4): 41-52.
[18] HU YH, WANG ZJ, LI DK, et al.Inhibition of CYP2E1 enhances hepatotoxicity of aqueous extract of Polygonum multiflorum and screening of toxic components[J]. Chinese Journal of Pharmac-ovigilance(中国药物警戒), 2021, 18(3): 206-212.
[19] WU L, HAN W, CHEN Y, et al.Gender differences in the hepatotoxicity and toxicokinetics of emodin: the potential mechanisms mediated by UGT2B7 and MRP2[J]. Molecular Pharmaceutics, 2018, 15(9): 3931-3945.
[20] LI TT, LI RH, LIU ZX, et al.Hepatotoxicity evaluation of susceptible substances of Polygonum multiflorum based on 3D organ like culture[J]. Journal of Pharmacy(药学学报), 2017, 52(7): 1048-1054.
[21] WANG Q, DAI Z, ZHANG YJ, et al.Study on hepatotoxicity of Polygonum multiflorum in vivo and in vitro based on biphasic metabolizing enzyme mediated bilirubin metabolism[J]. Chinese Journal of Pharmacy(中国药学杂志), 2016, 51(22): 1929-1933.
[22] YANG M, LIU T, FENG WH, et al.Study based on hepatotoxic substances of Polygonum multiflorum[J]. Chinese Journal of Traditional Chinese Medicine(中国中药杂志), 2016, 41(7): 1289-1296.
[23] WANG MX, WANG YG, XU HH, et al.Effects of emodin from Polygonum multiflorum on CYP sub enzyme expression and cytotoxicity in L02 hepatocytes[J]. Chinese Journal of Pharmacology(中国药理学通报), 2016, 32(11): 1543-1548.
[24] ZHANG ZY, YANG L, HUANG XY, et al.Regulation of THSG and anthraquinones in Polygonum multiflorum on CYP3A4 mediated by human pregnane X receptor[J]. Chinese Journal of Traditional Chinese Medicine(中国药学杂志), 2017, 42(24): 4827-4833.
[25] WANG ZJ, LI H, LI DK, et al.Effects of aqueous extract of Polygonum multiflorum and its main components on the mRNA expression of CYP1A2, CYP2C9 and CYP2E1 in human hepatocyte L02[J]. Chinese Herbal Medicine(中草药), 2017, 48(23): 4912-4920.
[26] WANG Q, LI Y, WANG YD, et al.Study on potential hepatotoxic components in Polygonum multiflorum based on molecular docking and rat liver microsomal inhibition experiment in vitro[J]. Drug Evaluation Study(药物评价研究), 2019, 42(4): 635-640.
[27] WEI J, CHEN J, FU L, et al.Polygonum multiflorum suppress bile acid synthesis by activating Fxr-Fgf15 signaling in the intestine[J]. Journal of Ethnopharmacology, 2018, 235: 472-480.
[28] TANG ZF, MA G, MEI QX.Effects of Radix Polygoni Multiflori on bilirubin uptake by hepatocytes and bile excretion before and after processing[J]. Shi Zhen Guo Yi Guo Yao(时珍国医国药), 2018, 29(3): 595-598.
[29] WANG T, WANG JY, ZHOU ZX, et al.Hepatotoxicity of Polygonum multiflorum aqueous extract in rats after continuous intragastric administration for 28 days -- Discussion on the mechanism of cholestasis[J]. Chinese Journal of Traditional Chinese Medicine(中国中药杂志), 2015, 40(11): 2163-2167.
[30] LI HP, ZHU HY, GAO X, et al.Study on the mechanism of liver injury of Polygonum multiflorum based on the functional inhibition of bilirubin related transporters in heterogeneous rats[J]. Chinese Journal of Traditional Chinese Medicine(中国中药杂志), 2017, 42(18): 3591-3595.
[31] KANG L.Study on the mechanism of liver injury induced by Polygonum multiflorum based on bile acid transporter and metabolic enzyme[D]. Wuhan: Huazhong University of Science and Technology, 2017.
[32] JING X, WU CQ, HAN G, et al.Study on cholestasis and related protein expression in Polygonum multiflorum liver injury model rats[J]. Drug Evaluation Research(药物评价研究), 2017, 40(5): 612-619.
[33] MAO HM, XIE LH, FAN X, et al.Effect of alcohol extract of Polygonum multiflorum on TLR4 / trif / IRF-3 signal pathway induced by lipopolysaccharide in rat liver[J]. International Journal of Pharmaceutical Research(国际药学研究杂志), 2016, 43(3): 496-503.
[34] LI C, RAO T, CHEN X, et al.HLA- B* 35: 01 allele is a potential biomarker for predicting Polygonum multiflorum- induced liver injury in humans[J]. Hepatology, 2019, 70(1): 346.
[35] LI Q, ZHAO KJ, ZHAO YL, et al.Study on multiple organ injury in rats induced by high-dose alcohol extract of Polygonum multiflorum[J]. Global Traditional Chinese Medicine(环球中医药), 2013, 6(1): 1-7.
[36] YANG JB, LI W F, LIU Y, et al.Acute toxicity screening of different extractions, components and constituents of Polygonum multiflorum. on zebrafish (Danio rerio) embryos in vivo[J]. Biomed Pharmacother, 2018, 99: 205-213.
[37] WANG Q, ZHANG XH, WEN HR, et al.Study on potential hepatot-oxicity of main monomers of Polygonum multiflorum based on liver microstructure[J]. Chinese Journal of Traditional Chinese Medicine(中国中药杂志), 2020, 45(12): 2954-2959.
[38] QUAN YY, ZHOU YM, LIU MC, et al.Screening the material basis of hepatotoxicity of Polygonum multiflorum by zebrafish model[J]. Chinese Journal of Experimental Prescriptions(中国实验方剂学杂志), 2019, 25(6): 52-57.
[39] PAN YZ, LI QJ, ZHANG Q, et al.Evaluation of heterogeneous liver injury of CIS and trans stilbene glycosides based on composite cell model[J]. Journal of Pharmacy(药学学报), 2021, 56(3): 808-815.
[40] SUN M, YU QW, XIANG T, et al.Stilbene glycoside disturbs bile acid balance and inhibits phospholipid secretion to induce liver injury[J]. Chinese Journal of Traditional Chinese Medicine(中国中药杂志), 2021, 46(1): 139-145.
[41] MA Z, ZHAO JR, DONG RR, et al.Hepatotoxicity study of extracts and main components in Polygonum multijiorum using high content analysis[J]. Chinese Herbal Medicine(中草药), 2016, 47(22): 4021-4029.
[42] PANIS B, WONG DR, HOOYMANS PM, et al.Recurrent toxic hepatitis in a caucasian girl related to the use of Shou-Wu-piana Chinese herbal preparation[J]. Journal of Pediatric Gastro-enterology and Nutrition, 2005, 41(2): 256-258.
[43] LI YL.Effects of Tannin in Polygonum multiflorum and its different ratio with stilbene glycoside on rat liver[D]. Shaanxi: Shaanxi College of Traditional Chinese Medicine, 2010.
[44] WANG L.Effects of different ratios of tannin, anthraquinone and stilbene glycoside in polygonum multiflorum on rat liver[D]. Shaanxi: Shaanxi College of Traditional Chinese Medicine, 2011.