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何首乌药代动力学与肝毒性概述。

Overview of Pharmacokinetics and Liver Toxicities of Radix Polygoni Multiflori.

机构信息

School of Pharmacy, The Chinese University of Hong Kong, Hong Kong 999077, China.

出版信息

Toxins (Basel). 2020 Nov 21;12(11):729. doi: 10.3390/toxins12110729.

Abstract

Radix Polygoni Multiflori (RPM), a traditional Chinese medicine, has been used as a tonic and an anti-aging remedy for centuries. However, its safe and effective application in clinical practice could be hindered by its liver injury potential and lack of investigations on its hepatotoxicity mechanism. Our current review aims to provide a comprehensive overview and a critical assessment of the absorption, distribution, metabolism, excretion of RPM, and their relationships with its induced liver injury. Based on the well-reported intrinsic liver toxicity of emodin, one of the major components in RPM, it is concluded that its plasma and liver concentrations could attribute to RPM induced liver injury via metabolic enzymes alteration, hepatocyte apoptosis, bile acids homeostasis disruption, and inflammatory damage. Co-administered 2,3,5,4'-tetrahydroxystilbene-2---D-glucopyranoside in RPM and other drugs/herbs could further aggravate the hepatotoxicity of emodin via enhancing its absorption and inhibiting its metabolism. To ensure the safe clinical use of RPM, a better understanding of the toxicokinetics and effect of its co-occurring components or other co-administered drugs/herbs on the pharmacokinetics of emodin is warranted.

摘要

何首乌(RPM)是一种传统中药,几个世纪以来一直被用作滋补品和抗衰老药物。然而,由于其具有潜在的肝损伤风险,且其肝毒性机制尚未得到充分研究,可能会阻碍其在临床实践中的安全有效应用。我们目前的综述旨在全面概述和评估 RPM 的吸收、分布、代谢、排泄及其与诱导肝损伤的关系。基于何首乌的主要成分大黄素具有内在肝毒性这一已充分报道的事实,可得出结论,其在血浆和肝脏中的浓度可能通过代谢酶的改变、肝细胞凋亡、胆汁酸稳态的破坏和炎症损伤导致 RPM 诱导的肝损伤。在 RPM 及其他药物/草药中共同给予 2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷,可通过增强其吸收和抑制其代谢,进一步加重大黄素的肝毒性。为确保 RPM 的安全临床应用,有必要更好地了解其共存成分或其他共同给予的药物/草药对大黄素药代动力学的毒代动力学和影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92b0/7700391/66356aa598aa/toxins-12-00729-g001.jpg

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