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首页> 外文期刊>RSC Advances >Potential metabolism determinants and drug–drug interactions of a natural flavanone bavachinin
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Potential metabolism determinants and drug–drug interactions of a natural flavanone bavachinin

机译：潜在的新陈代谢决定因素和天然黄酮类白杨蛋白的药物 - 药物相互作用

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Bavachinin, a natural bioactive flavanone, is reported to have many pharmacological proprieties, especially anti-osteoporosis activity. Here we aim to determine the roles of cytochrome P450s (CYP), UDP-glucuronosyltransferases (UGT), and efflux transporters in metabolism and drug–drug interactions (DDI) of bavachinin. Phase I metabolism and glucuronidation were performed by human liver microsomes (HLM) and human intestine microsomes (HIM). Reaction phenotyping was used to identify the main CYPs and UGTs. Gene silencing methods were employed to investigate the roles of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs) in HeLa1A1 cells. Inhibition mechanisms towards CYPs and UGTs were explored through kinetic modeling. Three phase I metabolites ( M1–M3 ) and one glucuronide ( G1 ) were detected after incubation of bavachinin with HLM and HIM. The intrinsic clearance (CL _(int) ) values of M1 and G1 by HLM were 89.4 and 270.2 μL min ~(?1) mg ~(?1) , respectively, while those of M3 and G1 by HIM were 25.8 and 247.1 μL min ~(?1) mg ~(?1) , respectively. CYP1A1, 1A2, 1B1, 2C8, 2C19, and UGT1A1, 1A8 participated more in bavachinin metabolism. The metabolism showed marked species difference. BCRP and MRP4 were identified as the main contributors. Bavachinin displayed potent inhibitory effects against several CYP and UGT isozymes ( K _(i) = 0.28–2.53 μM). Bavachinin was subjected to undergo metabolism and disposition by CYPs, UGTs, BCRP, MRP4, and was also a potent non-selective inhibitor against several CYPs and UGTs.
机译：据报道，Bavachinin，一种天然生物活性黄酮，有许多药理专题，尤其是抗骨质疏松活性。在这里，我们的目的是确定细胞色素P450s（CYP），UDP-葡糖醛糖基糖基转移酶（UGT）和流出转运蛋白在组成的代谢和药物 - 药物相互作用（DDI）中的作用。 I阶段I代谢和葡糖醛化由人肝微粒体（HLM）和人肠微粒体（HIM）进行。反应表型用于鉴定主要CYPS和UGT。使用基因沉默方法来研究乳腺癌抗性蛋白（BCRP）和多药抗性相关蛋白（MRP）在HelA1A1细胞中的作用。通过动力学建模探讨了CYPS和UGT的抑制机制。在孵育Bavachinin与HLM和HEM后，检测到三相i代谢物（M1-M3）和一个葡糖醛酸葡萄糖（G1）。通过HLM的M1和G1的固有间隙（Cl _（int））值分别为89.4和270.2μlmin〜（Δ1）mg〜（Δ1），而他的M3和G1的含量分别为25.8和247.1μL分别分别〜（？1）mg〜（？1）。 CYP1A1,1A2,1B1,2C8,2C19和UGT1A1,1A8在Bavachinin新陈代谢中参加了更多。新陈代谢显示出标记的物种差异。 BCRP和MRP4被确定为主要贡献者。 Bavachinin对几种Cyp和UGT同工酶显示有效的抑制作用（K _（i）=0.28-2.53μm）。受Bavachinin经受CYPS，UGTS，BCRP，MRP4的代谢和处理，并且还具有抗含有几种CYPS和UGT的有效的非选择性抑制剂。

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