基于IL-6R运用分子对接筛选红芪防护BMSCs的活性成分

Screening for active components in Radix Hedysari that protect bone marrow stromal cells using molecular docking based on IL-6R

摘要:

目的：通过分子对接筛选红芪防护白介素-6（interleukin-6，IL-6）诱导后骨髓间充质干细胞（bone mesenchymal stem cells，BMSCs）生物学特性稳定的活性成分。方法：选取43个红芪小分子化合物为配体，以白介素-6受体（interleukin-6 receptor，IL-6R）为靶蛋白，运用Schroding2015 软件Glide模块进行对接，选取对接打分较好且符合类药五原则的小分子化合物，MST检测筛选所得小分子化合物与IL-6R的结合亲和力，拟合结合曲线，计算结合程度。结果：分子对接筛选出与IL-6R在空间形状匹配较好且符合类药五原则的小分子化合物槲皮素、维斯体素、龙胆山酮酚，MST实验得到3个小分子化合物中槲皮素、维斯体素与IL-6R有较好的结合亲和力。结论：槲皮素、维斯体素可能是中药红芪发挥维持IL-6诱导后BMSCs生物学特性稳定的活性成分。

Abstract:

Objective：To screen out the active components in Radix Hedysari that maintain the biological stability of bone marrow stromal cells（BMSCs） induced by interleukin-6（IL-6） using molecular docking. Methods：The glide module of Schroding2015 soft－ware was used for molecular docking with 43 small-molecule compounds of Radix Hedysari as ligands and interleukin-6 receptor （IL-6R） as a target protein；small-molecule compounds with relatively good docking scores and having drug-likeness were selected and tested for binding affinity for IL-6R by microscale thermophoresis（MST）；then the binding curves were fitted and the binding levels were calculated. Results：Small-molecule compounds with a relatively good geometrical match with IL-6R and having drug-likeness screened out by molecular docking were quercetin，vestitol，and 1，5，8-trihydroxy-3-methoxy-9H -xanthen-9-one，among which the former two showed relatively good binding affinity for IL6R in the MST assay. Conclusion：Quercetin and vestitol may be the active components in Radix Hedysari that maintain the biological stability of BMSCs induced by IL-6.