基于分子对接与Caco-2细胞模型研究马钱苷元的转运特性  

Study on the Transportion Properties of Loganetin Based on Molecular Docking and Caco-2 Cell Model

作　　者：左芳[1] 魏志成[1] 黄文戈 王平[1] 孟宪丽[1] 张艺[1] ZUO Fang;WEI Zhi-cheng;HUANG Wen-ge;WANG Ping;MENG Xian-li;ZHANG Yi(Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China)

机构地区：[1]成都中医药大学,四川成都611137

出　　处：《中药材》2017年第10期2413-2418,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金(81274193)

摘　　要：目的:评价马钱苷元的转运特性及P-gp抑制剂对其转运的影响。方法:采用分子对接法预测马钱苷元与P-gp的结合方式及作用能力的强弱,建立Caco-2细胞单层模型,研究马钱苷元在模型中的双向转运,考察时间、药物浓度及P-gp转运蛋白抑制剂对其吸收的影响。运用高效液相色谱法检测药物浓度,计算其表观渗透系数。结果:分子对接结果显示,当对接蛋白为4F4C时,维拉帕米与马钱苷元的对接自由能值存在较大差异,马钱苷元与P-gp通过氢键及疏水作用形成不稳定的复合物;马钱苷元在Caco-2细胞单层模型的双向跨膜转运过程中,均呈现透过率下降趋势,具有相同的吸收特征及时间与浓度依赖性。Papp(BL→AP)与Papp(AP→BL)无显著性差异(P>0.05),且无明显方向性,随着时间增加Papp减小;P-gp蛋白抑制剂对马钱苷元转运无显著影响(P>0.05)。结论:马钱苷元的跨膜转运方式为被动转运,且分子对接与Caco-2模型结果均揭示了马钱苷元可能不是P-gp的底物,不存在P-gp转运蛋白的外排作用。Objective：To evaluate the transportion properties of loganetin and the effect of P-glycoprotein （P-gp） inhibitor on its transportion. Methods：The molecular docking method was used to predict the binding mode and the ability of loganetin and P-gp, the Caco-2 cell monolayer model was established to study the effect of bidirectional transportion, and the time, drug concentration and P-gp transporter inhibitor on the uptake of loganetin in the model was measured. Drug concentration was measured by HPLC method, and its apparent permeability coefficient was calculated. Results ：The results of molecular docking showed that there was a large difference in the docking free energy of verapamil and loganetin when the protein was 4F4C ,loganetin and P-gp form irreversible complexes by hydro- gen bonding and hydrophobic interaction ; the process of loganetinin of bi-directional transmembrane transportion of Caco-2 cell monolayer model showed a decline in transmittance, and had the same absorption characteristics which showed the time and concentration dependence. There was no significant difference between Papp（ BL→AP） and P app （AP→BL） （P〉0. 05）. There was no obvious direction, as time increases P app decreased, P-gp protein inhibitor had no significant effect on the transfer of loganetin （P〉 0. 05 ）. Conclusion：The results suggest that loganetin is transported by passive transport, and the results of molecular docking and Caco-2 model revealed that the loganetin is not the substrate of P-gp, and there is no efflux function of the P-gp transporter.

关 键 词：CACO-2细胞单层模型 分子对接 马钱苷元 转运 P-转运蛋白 

分 类 号：R285.5[医药卫生—中药学]