基于网络药理学和分子对接探讨桑枝改善高尿酸血症的作用机制

Study on the Mechanism of Mulberry Twig Improving Hyperuricemia Based on Network Pharmacology and Molecular Docking

目的:探讨桑枝(mulberry twig)治疗高尿酸血症(HUA)的可能作用靶点及机制。方法:于TCMSP、Batman-TCM、PubMed、CNKI等数据库进行检索,获取桑枝组分群,借助SwissTargetPrediction及PharmMapper等平台获取桑枝成分靶点;并利用GeneCards和OMIM在线平台收集整理HUA相关靶点;将HUA靶点与桑枝组分靶点取交集,得到共有靶点;利用STRING官方平台和Cytoscape软件获取蛋白互作网络图,并借助后者获取“化合物-靶点-通路”网络作用图;采取DAVID平台展开GO和KEGG富集分析;借助分子对接(Molecular docking)手段对分析结果加以验证。结果:筛选出桑枝潜在活性组分45个,组分靶点620个,HUA相关靶点1277个,共有靶点128个,经网络拓扑分析,得到VEGFA、SRC、PIK3CA、MAPK1、IL6、TNF等13个核心靶点以及木犀草素、槲皮素、环桑色烯、桑辛素M、桑色素、山奈酚、异鼠李素等10个活性组分。GO富集分析条目共获取295条(P<0.01),其中,生物过程(BP)共212个,主要包括细胞增殖正相调控、凋亡过程负相调控等;细胞组成(CC)共31个,靶点主要存在于质膜及细胞质等;分子功能(MF)共52个,主要涉及蛋白质结合、ATP结合等;KEGG富集共获取信号通路78条(P<0.01),主要包括Cancer、TNF、TRP、Toll-like receptor等信号通路。分子对接结果表明潜在活性组分与核心靶点结合优良。结论:本研究初步表明桑枝治疗HUA作用具有多组分、多靶点、多信号通路的特点,为后期深入研究桑枝潜在活性组分治疗HUA的分子机制奠定科学依据。

Objective: To explore the possible target and mechanism of mulberry twig in the treatment of hyperuricemia(HUA). Methods: Batman-TCM, TCMSP, PubMed, CNKI databases were used to obtain components of mulberry twig,component-related targets were collected through SwissTargetPrediction and PharmMapper online analysis platform. HUA targets were collected through GeneCards and OMIM databases. The intersection of disease targets and component targets was taken to obtain shared targets, protein interaction networks were constructed using the STRING database and the Cytoscape software, the compound-target-pathway network was constructed by Cytoscape software. The GO and KEGG enrichment analysis were performed using the DAVID database. Molecular docking was used to verify the results. Results:A total of 45 active components of mulberry twig, which corresponding to 620 targets, 1277 related disease targets of HUA,128 intersecting targets for active components and HUA were screened out. After topological analysis, there were 13 core targets including VEGFA, SRC, PIK3CA, MAPK1, IL6, TNF, etc. And 10 active components including Luteolin, Quercetin,Cyclomulberrochromene, Moracin M, Morin, Kaempferol, Isorhamnetin, etc. 295 GO entries(P<0.01) and 78 KEGG(P<0.01) signal pathways were obtained by enrichment analyses. Among them, there are 212 biological processes(BP),which mainly included positive regulation of cell proliferation and negative regulation of apoptosis processes, 31 cell composition(CC), with targets mainly located in the plasma membrane and cytoplasm, molecular functions(MF) 52 in total, mainly related to protein binding, ATP binding, etc. KEGG enrichment analysis mainly involved such signaling pathways as Cancer, TNF, TRP and Toll-like receptor. Molecular docking revealed a good binding activity of the main active components to the core targets. Conclusions: This study preliminarily showed that the treatment of HUA with mulberry twig had the characteristics of multi-component, multi-target and multi-signal pathway, which provided a scientific basis for further study on the molecular mechanism of the treatment of HUA with the potential active components of mulberry twig.