槐杞黄颗粒干预狼疮性肾炎的物质基础与作用机制：网络药理学和分子对接技术

Material basis and mechanism of Huaiqihuang Granule in intervention of lupus nephritis：network pharmacology and molecular docking technology

关键词:  槐杞黄颗粒  狼疮性肾炎  网络药理学  分子对接  靶点  通路  机制

Key words:  Huaiqihuang Granule  lupus nephritis  network pharmacology  molecular docking  target  signal path way  mechanism

摘要:

[目的] 基于网络药理学和分子对接技术探究槐杞黄颗粒干预狼疮性肾炎的物质基础与作用机制。[方法] 通过TCMSP、BATMAN-TCM获取槐杞黄颗粒的主要活性成分及作用靶点；通过GeneCards、OMIM、TTD获取狼疮性肾炎疾病靶点；利用VENNY平台获取药物和疾病的交集靶点；运用Cytoscape软件构建药物-活性成分-交集靶点-疾病网络图；将交集靶点录入STRING平台和Cytoscape软件中构建蛋白互作网络图；利用Metascape平台进行GO功能富集分析和KEGG通路富集分析；利用AutoDock Tools软件进行分子对接操作；最后利用Pymol软件对分子对接结果进行可视化分析。[结果] 共获取到56个槐杞黄颗粒的有效成分和211个成分作用靶点，其中核心活性成分以槲皮素、山柰酚、黄芩素、β-谷甾醇、黄豆黄素等作为代表；获取到狼疮性肾炎的疾病靶点1 822个；得到117个药物与疾病的交集靶点；通过构建蛋白互作网络图获取到核心靶点以血管内皮生长因子A（VEGFA）、c-fos原癌基因蛋白（FOS）、基质金属蛋白酶-9（MMP-9）、环氧化酶2（PTGS2）、靶向核因子κB抑制剂α（NFKBIA）等作为代表；GO功能富集分析共获取1 926条结果，KEGG通路富集分析得到195条结果，涉及到的主要通路以糖尿病并发症中的糖基化终末产物（AGE）-糖基化终末产物受体（RAGE）信号通路、肿瘤坏死因子（TNF）信号通路、白细胞介素（IL）-17信号通路、辅助性T 细胞17（Th17）细胞分化信号通路、低氧诱导因子（HIF-1）信号通路、磷脂酰肌醇3激酶（PI3K） -蛋白激酶B（Akt）信号通路等为主。分子对接的结果显示，β-谷甾醇与MMP-9、VEGFA、FOS，槲皮素与VEGFA、FOS，黄豆黄素与FOS，山奈酚与MMP-9等对接后结合能相对较小，提示这可能是槐杞黄颗粒干预狼疮性肾炎的关键作用途径。[结论] 研究初步揭示了槐杞黄颗粒可通过多成分、多靶点、多通路来干预狼疮性肾炎的进程。

Abstract:

[Objective] Based on network pharmacology and molecular docking technology，we explored the material basis and mechanism of Huaiqihuang Granules’ intervention in lupus nephritis. [Methods] TCMSP，BATMAN-TCM and other databases were used to obtain the main active ingredients and action targets of Huaiqihuang Granules，and then obtained the disease targets of lupus nephritis through GeneCards，OMIM，TTD and other databases. VENNY platform were used to obtain the intersection targets of drugs and diseases，and used the Cytoscape software to build a network diagram of drugs-active ingredients-intersection targets-diseases. Intersection targets into STRING platform and Cytoscape software were inputted to construct drug disease target protein interaction network diagram，and then Metascape platform were used to conduct enrichment analysis of GO and KEGG pathways. Finally，AutoDock Tools and Pymol software were used to perform molecular docking operations and visual analysis of docking results. [Results] A total of 56 active components and 211 target components of Huaiqihuang Granules were obtained，among which quercetin，kaempferol，baicalein，beta-sitosterol，glycitein are representative. The 1 822 disease targets of lupus nephritis were obtained. The 1 822 disease targets of lupus nephritis and 117 intersection targets of drugs and diseases were obtained. Core targets are obtained by constructing protein interaction network diagram，represented by VEGFA，FOS，MMP-9，PTGS2，NFKBIA，etc. A total of 1 926 results were obtained from GO enrichment and 195 results were obtained from KEGG pathway enrichment analysis. The main pathways involved are AGE-RAGE signal pathway，TNF signal pathway，IL-17 signal pathway，Th17 cell differentiation signal pathway，HIF-1 signal pathway，PI3K-Akt signal pathway，etc. The results of molecular docking showed that the binding energy of beta-sitosterol to MMP-9，VEGFA，FOS，quercetin to VEGFA，FOS，glycitein to FOS，kaempferol to MMP-9 after docking was relatively small，suggesting that this may be a key pathway for Huaiqihuang Granules to intervene in lupus nephritis. [Conclusion] This study preliminarily revealed that Huaiqihuang Granules can interfere with the process of lupus nephritis through multiple components，multiple targets and multiple pathways.