肠道“药物代谢酶-外排转运体偶联”对黄酮类化合物生物利用度影响的研究进展  

Recent advances in intestinal “drug-metabolizing enzyme-efflux transporter coupling” and effect on bioavailability of flavonoids

作　　者：师少军[1] SHI Shao-Jun(Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Wuhan 430022, China)

机构地区：[1]华中科技大学同济医学院附属协和医院药学部

出　　处：《中国医院药学杂志》2019年第20期2107-2112,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金面上项目(编号:81874326);湖北省卫健委中医药科研项目(重点项目)(ZY2019Z004);国家重点研发计划资助(编号:2017YFC0909900)

摘　　要：黄酮类化合物为广泛存在于食物和药物中的一类多酚化合物,具有多种药理作用,但其生物利用度低限制了其临床应用,这与其肠道吸收和代谢密切相关。黄酮类化合物主要在肠道吸收,并经Ⅱ相药物代谢酶:葡萄糖醛酸转移酶(UGTs),硫酸转移酶(SULTs)和谷胱甘肽-S-转移酶(GSTs)广泛代谢为Ⅱ相代谢产物,其极性增加,难以通过被动扩散穿透肠上皮细胞膜。肠道外排转运体P-糖蛋白(P-gp)、乳腺癌耐药蛋白(BCRP)、多药耐药相关蛋白(MRPs)作为一个"旋转门",可调控肠上皮细胞内Ⅱ相代谢物外排至肠腔或进入体循环。本文对黄酮类化合物在肠道处置以及肠道药物代谢酶-外排转运体偶联进行了探究,这种偶联作用可显著影响黄酮类化合物生物利用度,进而影响其临床疗效与毒副作用。阐明肠道代谢酶-外排转运体偶联作用及其机制,将为提高黄酮类化合物体内生物利用度和增加其临床疗效奠定基础。Flavonoids are a kind of polyphenolic compounds, which are widely distributed in food and drugs with a variety of pharmacological effects. However,their poor oral bioavailability limits their clinical application in humans, which is closely related to intestinal absorption and metabolism. Flavonoids are mainly absorbed in the intestine, and are extensively metabolized in humans via the phase Ⅱ drug-metabolizing enzymes: UDP-glucuronosyltransferases(UGTs), sulfotransferases(SULTs) and glutathione S-transferases(GSTs) to their Ⅱ phase metabolites, which could increase its polarity.Phase Ⅱ conjugates cannot traverse through the cellular membrane by passive diffusion in enterocytes due to their high polarity. The intestinal efflux transporters: P-glycoprotein(P-gp), breast cancer resistance protein(BCRP) and multidrug resistance-associated proteins(MRPs) as a "revolving door", actively transport the phase Ⅱ metabolites from enterocytes to the intestinal lumen or the systemic circulation. This review provides an insight into flavonoids dispostion and the role of drug-metabolizing enzyme-efflux transporter coupling is investigated. This coupling effect can significantly affect the bioavailability of flavonoids, and then affect their clinical efficacy and side effects. Elucidation of the action and mechanism of intestinal metabolic enzymes-efflux transporters coupling will lay a foundation for improving the bioavailability of flavonoids in vivo and increasing their clinical efficacy.

关 键 词：黄酮类化合物 生物利用度 肠道 药物代谢酶 外排转运体 偶联作用 

分 类 号：R96[医药卫生—药理学]