基于网络药理学与分子对接探讨葶苈子抗抑郁症的潜在作用机制  

Potential Mechanisms of Semen Lepidii in Antidepressant Effects Based on Network Pharmacology and Molecular Docking

作　　者：窦成福[1] 罗禹 李治芳[3] DOU Chengfu;LUO Yu;LI Zhifang(Rehabilitation Hospital,the First People’s Hospital of Yinchuan,Second Clinical Medical College of Ningxia Medical University,Yinchuan 750001,China;School of Pharmacy,University of Electronic Science and Technology Hospital,Chengdu 611730,China;School of Pharmacy,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]银川市第一人民医院康复医院,宁夏医科大学第二临床医学院,银川750001 [2]电子科技大学医院药剂科,成都611730 [3]宁夏医科大学药学院,银川750004

出　　处：《宁夏医科大学学报》2024年第11期1164-1172,共9页Journal of Ningxia Medical University

摘　　要：目的基于网络药理学和分子对接方法,探索葶苈子在治疗抑郁症中分子层面的潜在作用机制。方法利用TCMSP、GeneCards、DisGeNET等数据库,在获取葶苈子有效活性成分、作用靶点和抑郁症疾病相关靶点的基础上,取药物靶点同疾病靶点的交集,对葶苈子治疗抑郁症的靶点进行蛋白质-蛋白质相互作用网络(PPI)分析,筛选出核心靶点。通过基因本体(GO)功能和京都基因与基因组数据库(KEGG)通路富集分析药物及疾病的信号通路,并对网络中度值较高的药效成分与核心靶点进行分子对接及可视化分析。结果检索到葶苈子的药物有效成分12种,靶点基因158个,抑郁症疾病相关靶点共1712个,共交集到86个靶点基因,筛选后共得到9个核心靶点基因。GO功能富集分析显示,葶苈子主要参与细胞凋亡和增殖、炎性反应、活性氧代谢过程的调节等生物过程;KEGG通路富集分析结果显示,中药葶苈子与丝裂原活化蛋白激酶、哺乳动物雷帕霉素靶蛋白、磷脂酰肌醇-3-激酶/丝氨酸、细胞质DNA感应途径、胆碱能突触、炎性介质对TRP通道等关系紧密。结论葶苈子可能通过多成分、多靶点和多通路的作用机制治疗抑郁症,这将为进一步探究其临床治疗提供理论基础。Objective To explore the potential molecular mechanisms of Semen Lepidii in treating depression using network pharmacology and molecular docking approaches.Methods The main targets of Semen Lepidii were intersected with those of disease targets and the protein-protein interaction(PPI)analysis of targets of Semen Lepidii in the treatment of depression was conducted to select the core targets,on the basis of the effective active ingredients and targets of Semen Lepidii and depression-related targets obtaining by using TCMSP,GeneCards,DisGeNET data base and et al.gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)enrichment were used to analyze the signaling pathways of drugs and diseases,and molecular docking and visual analysis were performed on the pharmacodynamic components and the core action targets.Results 12 active compounds,158 target genes,1712 depression-related targets and 86 intersecting target genes were dientified.Nine core target genes were selected.GO enrichment analysis revealed that Semen Lepidii is primarily involved in biological processes such as the regulation of apoptosis and proliferation,inflammatory responses,and reactive oxygen species metabolism.KEGG enrichment analysis indicated that the active components of Semen Lepidii were closely related to pathways such as MAPK,mTOR,PI3K/AKT,cytosolic DNA sensing pathways,cholinergic synapses and TRP channels involved in inflammatory mediator responses.Conclusion Semen Lepidii may treat depression through multi-component,multi-target and multi-pathway mechanisms,which provide a theoretical foundation for further exploration of its clinical treatement.

关 键 词：葶苈子 抑郁症 网络药理学 分子对接 作用机制 

分 类 号：R91[医药卫生—药学]