Division of Biomedical Science, School of Pharmacy, University of Nottingham Malaysia Campus, Semenyih, Selangor Darul Ehsan, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Drug Metab Pers Ther. 2021 Aug 17;37(1):55-67. doi: 10.1515/dmpt-2021-1000196.
Khat, a natural amphetamine-like psychostimulant plant, are widely consumed globally. Concurrent intake of khat and xenobiotics may lead to herb-drug interactions and adverse drug reactions (ADRs). This study is a continuation of our previous study, targeted to evaluate the inhibitory effects of khat ethanol extract (KEE) on human cytochrome (CYP) 1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, and CYP3A5, major human drug metabolizing enzymes.
fluorescence enzyme assays were employed to assess CYPs inhibition with the presence and absence of various KEE concentrations.
KEE reversibly inhibited CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2 and CYP3A5 but not CYP1A2 with IC values of 25.5, 99, 4.5, 21, 27, 17, and 10 μg/mL respectively. No irreversible inhibition of KEE on all the eight CYPs were identified. The K values of CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2 and CYP3A5 were 20.9, 85, 4.8, 18.3, 59.3, 3, and 21.7 μg/mL, respectively. KEE inhibited CYP2B6 via competitive or mixed inhibition; CYP2E1 via un-competitive or mixed inhibition; while CYP2A6, CYP2C8, CYP2C19, CYP2J2 and CYP3A5 via non-competitive or mixed inhibition.
Caution should be taken by khat users who are on medications metabolized by CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, and CYP3A5.
阿拉伯茶，一种天然的安非他命样精神兴奋剂植物，在全球范围内广泛消费。阿拉伯茶与其他外源性物质同时摄入可能导致草药-药物相互作用和药物不良反应（ADR）。本研究是我们之前研究的延续，旨在评估阿拉伯茶乙醇提取物（KEE）对人细胞色素（CYP）1A2、CYP2A6、CYP2B6、CYP2C8、CYP2C19、CYP2E1、CYP2J2 和 CYP3A5 的抑制作用，这些酶是人类主要的药物代谢酶。
采用荧光酶法评估有无不同 KEE 浓度存在时 CYP 的抑制情况。
KEE 可逆性抑制 CYP2A6、CYP2B6、CYP2C8、CYP2C19、CYP2E1、CYP2J2 和 CYP3A5，但对 CYP1A2 无抑制作用，IC 值分别为 25.5、99、4.5、21、27、17 和 10μg/mL。未发现 KEE 对所有 8 种 CYP 有不可逆抑制作用。CYP2A6、CYP2B6、CYP2C8、CYP2C19、CYP2E1、CYP2J2 和 CYP3A5 的 K 值分别为 20.9、85、4.8、18.3、59.3、3 和 21.7μg/mL。KEE 通过竞争性或混合性抑制抑制 CYP2B6；通过非竞争性或混合性抑制抑制 CYP2E1；而通过非竞争性或混合性抑制抑制 CYP2A6、CYP2C8、CYP2C19、CYP2J2 和 CYP3A5。
服用 CYP2A6、CYP2B6、CYP2C8、CYP2C19、CYP2E1、CYP2J2 和 CYP3A5 代谢的药物的阿拉伯茶使用者应谨慎。
