基于生信分析、分子对接及分子动力学研究枸杞子中活性成分改善胰岛素抵抗的作用机制＊

目的 通过生信分析、分子对接及分子动力学技术研究枸杞子中活性成分改善胰岛素抵抗的作用机制。方法 通过网站、数据库及文献检索获取枸杞子种有效成分及胰岛素抵抗的疾病靶点,并进行整理与筛选,预测枸杞子经筛选后活性成分改善胰岛素抵抗可能的作用靶点并进行生信分析。从CTD数据库选择5个胰岛素抵抗的重要蛋白受体,确定结合位点后分别与枸杞子符合筛选标准的有效成分用Auto Dock Vina进行分子对接,将对接结果中结合能低且具有继续研究意义的构象应用分子动力学技术进行进一步分析。结果 槲皮素、豆甾醇、谷甾醇、酸浆苦素A等27个化合物可能是枸杞子改善胰岛素抵抗的重要活性成分,涉及对化学,内源性物质的反应、神经元,细胞投射、蛋白质结合,G蛋白偶联受体活性等多个生物过程及钙离子、IL17、PI3K/Akt等多个信号通路;CCL2、INSR、NOS3、SIRT1、TNF是胰岛素抵抗的重要蛋白受体。某些枸杞子中经筛选的活性成分与重要蛋白受体的结合程度强,甚至优于罗格列酮。Stigmasterol-INSR、Lantadene A-NOS3作为有继续研究意义的构象进一步进行分子动力学模拟,结果均可以稳定地结合,是范德华势能和静电、氢键作用的共同结果。结论 枸杞子改善胰岛素抵抗是通过多成分、多靶点、多生物过程、多通路等多种途径实现的;枸杞子中活性成分与胰岛素抵抗重要蛋白受体的结合能力较强,改善胰岛素抵抗理论依据充足;生信分析、分子对接及分子动力学技术可以成为阐释单味药物作用机制的一种方便、普适、高效的方法,但需要结合一定的动物、临床或者细胞实验才能增强说服力。

Research on the Mechanism of Improving Insulin Resistance by Bioactive Components in Fructus Lycii Through Bioinformatics Analysis, Molecular Docking and Molecular Dynamics Technology

Objective To explore the mechanism of ameliorating insulin resistance by bioactive components in Fructus Lycii through bioinformatics analysis, molecular docking and molecular dynamics.Methods The effective components of Fructus Lycii and insulin resistance disease targets were obtained through website, database and bibliography retrieval, then screened and sorted out it to predict the possible targets of ameliorating insulin resistance of the bioactive components in Fructus Lycii, then conducted bioinformatics analysis. Five important protein receptors of insulin resistance were obtained from CTD database. After the binding sites were determined, the bioactive components that accorded with the screening criteria of Fructus Lycii were conducted molecular docking by the software of Auto Dock vina. The conformations with low binding energy in molecular docking results were proceeded analyzed by the technology molecular dynamics.Results There were 27 compounds including quercetin, stigmasterol, sitosterol, Physalin-A may be the important active components of Fructus Lycii that could improve insulin resistance, involving the reaction to chemistry and endogenous substances, neurons, cell projection, protein binding, G protein coupled receptor activity and many other biological processes as well as calcium ion, IL17, PI3K/Akt and many other signaling pathways. CCL2, INSR, NOS3, SIRT1, TNF were important protein receptors of insulin resistance. Some of the screened bioactive components of Fructus Lycii had strong binding degree with important protein receptors, even better than Rosiglitazone. Stigmasterol-INSR and Lantadene A-NOS3 as the conformations with proceed analyzed value were conducted by the technology molecular dynamics. The result shown it can be combined stably through VDWAALS potential energy, electrostatic interaction and hydrogen bonding interaction.Conclusion Fructus Lycii can ameliorate insulin resistance through multi-channel including multi-component, multi-target, multi biological process, multi-signal pathway. The bioactive components in Fructus Lycii has strong binding ability with important protein receptor of insulin resistance. It has sufficient theoretical basis for improving insulin resistance. Bioinformatics analysis, molecular docking and molecular dynamics technology can be a convenient, pervasive and efficient way to explain the mechanism of single drug, but it needs to be combined with animal and clinical experiments or cell experiment to enhance its persuasion.