基于网络药理学和分子对接探讨黄芪-丹参配伍治疗糖尿病肾病作用机制研究

UTILIZING NETWORK PHARMACOLOGY AND MOLECULAR DOCKING TO EXPLORE THE UNDERLYING MECHANISM OF RADIX ASTRAGALI AND RADIX SALVIAE IN DIABETIC NEPHROPATHY

目的 基于网络药理学和分子对接探讨黄芪-丹参配伍治疗糖尿病肾病作用机制研究。方法 通过中药系统药理学技术平台(TCMSP)获取黄芪、丹参有效成分和作用靶点,运用Cytoscape3.7.1构建成分-靶点-疾病靶点网络图,获取有效成分和DN交集基因,构建PPI网络,运用分子对接对筛选出的有效成分与核心靶基因进行分子对接验证。运用Bioconductor对靶基因进行GO生物学过程分析和KEGG通路分析。结果 通过分析黄芪、丹参共获得81个有效成分,获取交集基因22个,分子对接预测丹参酮ⅡA与MYC、VCAM1、CASP3有较强的结合活性,槲皮素和山奈酚与ADRB2有较强的结合活性。GO和KEGG富集分析显示,黄芪-丹参治疗DN主要参与糖尿病并发症AGE/RAGE、MAPK、HIF-1等多条信号通路等。结论 黄芪-丹参主要是通过活性成分槲皮素、山奈酚、木犀草素、丹参酮ⅡA等通过靶向ADRB2、CASP3、VCAM1、MYC等相关靶点,参与糖尿病并发症AGE/RAGE、MAPK、HIF-1等多条信号通路发挥治疗DN作用。

Objective: To study the molecular mechanism of diabetic nephropathy treated by Radix astragali and Radix salviae based on network pharmacology and molecular docking. Methods: The chemical components and putative targets of R. astragali and R. salviae were collected based on the TCMSP. Cytoscape3.7.1 software was used to construct the component-target-disease network. Based on the matching targets of related targets in R.astragali and R. salviae on DN, protein interaction network analysis was performed. Using the AutoDock Vina software, the candidate compounds were docked with the core targets. Finally GO biological process and KEGG were carried out. Results: In total, 81 active compounds of R. astragali and R. salviae were identified, of which22 ones were the targets for the treatment of DN. Molecular docking prediction showed that tanshinone ⅡA had a strong binding activity with MYC, VCAM1 and CASP3, quercetin and kaempferol had a strong binding activity with ADRB2. The main pathway included AGE/RAGE, MAPK, HIF-1signal pathway. Conclusion: Some active compounds of R. astragali and R. salviae, such as tanshinone ⅡA, luteolin, quercetin and kaempferol, play a role of alleviating DN by affecting AGE/RAGE, MAPK, HIF-1signal pathway. These pathways were primarily associated with the common targets of ADRB2, CASP3, VCAM1 and MYC.