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.Carboxylesteras...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.展开更多
基金the National Key Research and Development Program of China(2017YFC1700200,2017YFC1702000)the National Scientific and Technological Major Projects of China(2017ZX09101004)+3 种基金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).
文摘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.
