Nabekura Tomohiro, Yamaki Takeshi, Ueno Kazuyuki, Kitagawa Shuji
Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Higashi-jima, Akiha-ku, Niigata 956-8603, Japan.
Biochem Biophys Res Commun. 2008 May 2;369(2):363-8. doi: 10.1016/j.bbrc.2008.02.026. Epub 2008 Feb 14.
The effects of dietary plant sterols on human drug efflux transporters P-glycoprotein (P-gp, ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) were investigated using P-gp-overexpressing human carcinoma KB-C2 cells and human MRP1 gene-transfected KB/MRP cells. The effects of natural phytosterols found in foods, herbs, and dietary supplements such as beta-sitosterol, campesterol, stigmasterol, fucosterol, and z-guggulsterone were investigated. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-gp, increased in the presence of guggulsterone in KB-C2 cells. The efflux of rhodamine 123 from KB-C2 cells was inhibited by guggulsterone. Guggulsterone also increased the accumulation of calcein, a fluorescent substrate of MRP1, in KB/MRP cells. The ATPase activities of P-gp and MRP1 were stimulated by guggulsterone. These results suggest that guggulsterone, a natural dietary hypolipidemic agent have dual inhibitory effects on P-gp and MRP1 and the potencies to cause food-drug interactions.
利用过表达P-糖蛋白的人KB-C2癌细胞和转染人MRP1基因的KB/MRP细胞，研究了膳食植物甾醇对人药物外排转运体P-糖蛋白（P-gp，ABCB1）和多药耐药蛋白1（MRP1，ABCC1）的影响。研究了在食物、草药和膳食补充剂中发现的天然植物甾醇的作用，如β-谷甾醇、菜油甾醇、豆甾醇、岩藻甾醇和Z-古甾酮。在KB-C2细胞中，P-糖蛋白的荧光底物柔红霉素或罗丹明123的积累在古甾酮存在的情况下增加。古甾酮抑制了罗丹明123从KB-C2细胞中的外排。古甾酮还增加了MRP1的荧光底物钙黄绿素在KB/MRP细胞中的积累。古甾酮刺激了P-糖蛋白和MRP1的ATP酶活性。这些结果表明，作为一种天然膳食降血脂剂的古甾酮对P-糖蛋白和MRP1具有双重抑制作用，并且具有引起食物-药物相互作用的潜力。
