Carboxylesterases mediated herb-drug interactions:a systematic review  

作　　者：Dan-Dan Wang Yun-Qing Song Ya-Di Zhu Yi-Nan Wang Hai-Feng Li Guang-Bo Ge Ling Yang 

机构地区：[1]nstitute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,China [2]School of basic medical science,Shanghai University of Traditional Chinese Medicine,Shanghai,China

出　　处：《TMR Modern Herbal Medicine》2019年第1期25-35,共11页TMR现代中药

基　　金：the National Key Research and Development Program of China(2017YFC1700200,2017YFC1702000);the National Scientific and Technological Major Projects of China(2017ZX09101004);the National Natural Science Foundation of China(81703604,81773687 and 81573501);Program of Shanghai Academic/Technology Research Leader(18XD1403600);Shuguang Program(No.18SG40);Shanghai Education Development Foundation and Shanghai Municipal Education Commission,Project funded by China Postdoctoral Science Foundation(2017M621520,and 2018T110406).

摘　　要：Esterases participate in the metabolism of^10%of the clinical drugs that contain ester or amide bonds,but the esterases mediated drug/herb-drug interactions(DDIs or HDIs)have not been reviewed in depth.Carboxylesterases(CEs),the most abundant esterases expressed in the metabolic organ of mammals,play a pivotal role in hydrolysis of a variety of endogenous and xenobiotic esters.In the human body,two predominant carboxylesterases including hCE1 and hCE2 have been identified and extensively studied over the past decade.These two enzymes have been found with hydrolytic activity towards a variety of endogenous esters and ester-containing drugs.Recent studies have demonstrated that strong inhibition on hCEs may slow down the hydrolysis of CEs substrates,which may affect their pharmacokinetic properties and thus trigger potential DDIs or HDIs.Over the past decade,many herbal extracts and herbal constitutes have been found with strong inhibitory effects against CEs,and their potential risks on herb-drug interactions(HDIs)have also attracted much attention.This review focused on recent progress in hCEs mediated herb-drug interactions.The roles of hCEs in drug metabolism,the inhibitory capacities and inhibition mechanism of a variety of herbal extract and herbal constitutes against hCEs have been well summarized.Furthermore,the challenges and future perspectives in this field are highlighted by the authors.All information and knowledge presented in this review will be very helpful for the pharmacologists to deeper understand the metabolic interactions between herbal constituents and hCEs,as well as for clinical clinicians to reasonable use herbal medicines for alleviating hCEs-associated drug toxicity or avoiding the occurrence of clinically relevant hCEs-mediated HDIs.酯酶参与约10%临床药物(含有酯键或酰胺键)的代谢。但长期以来,酯酶介导的药物/草药相互作用(DDI或HDI)尚未得到深入研究。羧酸酯酶(CEs)是哺乳动物代谢器官中表达最丰富的一类酯酶,其在多种内源性和外源性酯类化合物的水解过程中发挥了重要作用。人体中主要分布了hCE1和hCE2两种羧酸酯酶亚型,其在过去十多年中被广泛研究。这两种羧酸酯酶已被证实参与多种内源性酯类化合物和外源性酯类药物的水解。最近研究表明,强效抑制hCEs可减缓CEs底物药物的水解,这可能影响它们的药代动力学行为,进而引发潜在的DDI或HDI。在过去十年中,已经发现多种草药提取物和草药成分对CEs具有强烈的抑制作用,同时它们带来的草药相互作用(HDI)潜在风险也引发了广泛关注。本综述重点介绍了hCEs介导的药物相互作用的最新研究进展,全文总结了hCEs在药物代谢中的作用,以及多种草药提取物和草药成分对hCEs的抑制能力和抑制机制。此外,作者还对该研究领域面临的挑战和未来的前景进行了展望。本综述中提供的所有信息和知识将有助于药理学家更深入地了解草药成分与hCEs间的代谢性相互作用,同时也有助于临床医生更加合理的使用草药进而减轻hCEs介导的药物毒性或避免发生具有临床意义的hCE介导的草药相互作用。

关 键 词：Human carboxylesterases(CEs) HCE1 hCE2 herb-drug interactions Natural inhibitors 

分 类 号：R[医药卫生]