基于网络药理学和分子对接探析槲皮素对抑郁的作用机制

Based on network pharmacology and molecular docking to explore the mechanism of quercetin on depression

应用网络药理学及分子对接技术探究槲皮素治疗抑郁的潜在机制。从SwissTargetPrediction、Superpred数据库中筛选出“槲皮素”相关靶点;从OMIM、Genecards数据库中筛选出“抑郁”的相关靶点。通过Jvenn获得二者的共同蛋白质靶点信息后,使用Cytoscape软件构建蛋白质互作网络,并对hub基因进行筛选。使用David平台对相同靶点进行GO、KEGG等富集分析。最后采用分子对接技术进行准确性检验。PPI网络中共有103个节点,536条边,其中SRC、MTOR、EGFR、AKT1、PTK2等靶点度值排名较高。GO、KEGG富集分析结果表明,槲皮素对抑郁的作用主要涉及凋亡过程的负向调节、信号转导、蛋白磷酸化反应等生物学过程。信号通路主要包括HIF-1、ErbB、磷脂酶D信号传导、神经营养素信号传导等。分子对接结果显示SRC、MTOR、AKT1等靶点与槲皮素结合程度较好,且在KEGG通路中富集。揭示了槲皮素作用于抑郁的潜在靶点及机制,以期望研制出治疗抑郁症新药物。

The study aims to clarify the potential mechanism of quercetin in the treatment of depression based on network pharmacology and molecular docking techniques.The corresponding protein targets of quercetin were screened from SwissTargetPrediction and Superpred databases;The genes associated with depression were screened out from OMIM and Genecards.Then,the Cytoscape3.9.1 software package was used to construct the PPI network and screen the hub gene;the DAVID platform was used to conduct Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Finally,molecular docking methods was used for accuracy check.There are 103 nodes and 536 edges in the PPI network,in which SRC,MTOR,EGFR,AKT1,and PTK2 have the highest degree value.GO and KEGG analysis show that the protective effect of quercetin on depression mainly involves the negative regulation of apoptosis,signal transduction,protein phosphorylation,and other biological processes.The signal pathways mainly include HIF⁃1,ErbB,phospholipase D,and neurotrophin signal transduction etc.Molecular docking confirm the high affinity between quercetin and its targets(SRC,AKT1,MTOR).And these targets are enriched in the KEGG pathway.This study reveals the potential targets and the molecular mechanism of quercetin in the treatment of depression,in order to develop new drugs for depression.