[关键词]
[摘要]
目的 研究淫羊藿苷元对临床重要转运体OAT1、OAT3、OATP1B1、OATP1B3、OCT1、OCT2、BCRP、BSEP和P-gp转运蛋白的抑制作用。方法 应用过表达各转运体的细胞株,检测淫羊藿苷元(0、0.03、0.10、0.30、1.00、3.00、10.00 μmol/L)对hOAT1介导的放射性同位素标记底物14C-对氨基马尿酸(14C-PAH)、hOAT3介导的3H-硫酸雌酮铵(3H-ES)、hOATP1B1介导的3H-ES、hOATP1B3介导的3H-雌二醇葡糖苷酸(3H-EG)、hOCT1介导的14C-溴化四乙胺(14C-TEA)、hOCT2介导的14C-TEA、hBCRP介导的3H-ES、MDR1介导的3H-地高辛(3H-Digoxin)、以及hBSEP介导的3H-牛黄胆酸盐(3H-TCA)转运活性的影响,计算淫羊藿苷元对不同转运蛋白的抑制作用的半数抑制浓度(IC50)。结果 与对照组比较,淫羊藿苷元0.3~10 μmol/L浓度对OAT3转运活性发挥显著抑制作用(P<0.05),0.1~10 μmol/L对P-gp有显著抑制作用;1~10 μmol/L浓度对OATP1B3和BCRP转运活性有显著抑制作用(P<0.05);3~10 μmol/L浓度对和OATP1B1转运活性有显著抑制作用(P<0.05);对OAT3和BCRP转运活性的IC50分别为4.97和8.15 μmol/L;对OAT1B1、OATP1B3、OCT2和P-gp的IC50均大于10 μmol/L,对OAT1、OCT1和BSEP转运活性无明显影响。结论 淫羊藿苷元对药物转运体OAT3和BCRP的抑制作用相对较强,对OAT1B1、OATP1B3、OCT2和P-gp也具有一定的抑制作用,对OAT1、OCT1和BSEP无显著抑制作用。
[Key word]
[Abstract]
Objective To research the inhibition of anhydroicaritin to the important clinical transporters including OAT1, OAT3, OATP1B1, OATP1B3, OCT1, OCT2, BCRP, BSEP, and P-gp. Method The transgenic cell lines overexpressing OAT1, OAT3, OATP1B1, OATP1B3, OCT1, OCT2, BCRP, BSEP, and P-gp were constructed, and the inhibition of anhydroicaritin (0, 0.03, 0.10, 0.30, 1.00, 3.00, and 10.00 μmol/L) on the different transporters were evaluated by the effects of anhydroicaritin on transport activity of the radiolabeled substrates of 14C-PAH, 3H-ES, 3H-ES, 3H-EG, 14C-TEA, 14C-TEA, 3H-ES, 3H-Digoxin, 3H-TCA mediated by hOAT1, hOAT3, OATP1B, hOATP1B3, hOCT1, hOCT2, hBCRP, MDR1,and hBSEP, respectively. The half maximal inhibitory concentration (IC50) of anhydroicartin to every transporters were calculated by the software Prism 5.0. Result Compared with control group, anhydroicaritin of 0.3 - 10 mol/L concentration had significant inhibitory effects on the transport activity of OAT3, BCRP, and OATP1B3 (P<0.05), and concentration of 0.1~10 and 1~10 μmol/L significantly inhibited the P-gp and OATP1B1 transport activity (P<0.05). The IC50 of anhydroicaritin to OAT3 and BCRP transport activity was 4.97 and 8.15 mol/L, respectively, and IC50 of OAT1B1, OATP1B3, OCT2, and P-gp were more than 10 μmol/L, and with no obvious effects on the transport activity of OAT1, OCT1, and BSEP. Conclusion Anhydroicaritin showed strong inhibition to OAT3 and BCRP, and showed certain inhibition to OATP1B1, OATP1B3, OCT2, and P-gp inordinately, but no inhibition to OAT1, OCT1, and BSEP.
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[基金项目]
国家自然科学基金重点项目(81430096);天津市科技支撑重点项目(17YFZCSY01170);国家青年自然科学基金(81503154)