基于网络药理学和分子对接探讨苦参碱在奶牛生产中的抗炎作用机制

Integrating Network Pharmacology and Molecular Docking to Explorer Mechanism of Anti-Inflammation of Matrine in Dairy Cow Production

本研究旨在应用网络药理学和分子对接技术探讨苦参碱在奶牛生产中的抗炎作用机制。登录中药系统药理学数据库与分析平台(TCMSP)数据库查找苦参碱的主要靶点,再登录PubChem以及PharmMapper数据库对苦参碱靶点进行补充,同时检索GeneCards和DisGeNET数据库获得炎症相关靶点,获取苦参碱与炎症交集靶点即为苦参碱治疗奶牛炎症的候选靶点;通过STRING数据库输入苦参碱抗炎交集靶点并构建蛋白质-蛋白质相互作用(PPI)网络,通过Cytoscape 3.9.1软件中的CytoNCA模块筛选该网络核心靶点,利用David数据库对苦参碱抗炎靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。通过Autodock Tools软件对核心靶点以及活性成分进行分子对接。结果表明,苦参碱发挥抗炎作用的相关靶点有71个;PPI网络分析结果发现白蛋白(ALB)、肿瘤坏死因子(TNF)、MYC原癌基因碱性螺旋-环-螺旋转录因子(MYC)、半胱氨酸-天冬氨酸蛋白酶3(CASP3)、周期蛋白D1(CCND1)、CD44和白细胞介素-6(IL-6)是苦参碱抗炎作用的核心靶点;GO功能富集分析表明该靶点涉及62种生物学过程(BP)、16种细胞组分(CC)和12种分子功能(MF);KEGG通路富集分析共获得71条信号通路。分子对接预测结果表明苦参碱与关键核心靶点稳定结合,相互作用较好。本研究利用网络药理学和分子对接技术揭示了苦参碱的多靶点及多通路发挥抗炎作用的机制,为苦参碱在奶牛生产中的进一步临床应用提供了参考。

The aim of this study was to investigate the anti-inflammatory mechanism of matrine in dairy production using network pharmacology and molecular docking techniques.The main targets of matrine were searched by logging into the Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)database and supplemented by logging into PubChem and PharmMapper databases.At the same time,inflammation-related targets were obtained by searching GeneCards and DisGeNET databases,and the intersection target of matrine and inflammation is a candidate target of matrine for the treatment of inflammation in dairy cows.Matrine anti-inflammatory intersection targets were input into STRING database and protein-protein interaction(PPI)network was constructed.Core targets of this network were screened by CytoNCA module in Cytoscape 3.9.1 software.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of matrine anti-inflammatory targets were performed using David database.The core targets and active components were docked by Autodock Tools.The results showed that there were 71 targets related to matrine’s anti-inflammatory effect.PPI network analysis showed that albumin(ALB),tumor necrosis factor(TNF),MYC proto-oncogene basic helix-loop helix transcription factor(MYC),cysteine-aspartate proteinase 3(CASP3),cyclin D1(CCND1),CD44 and interleukin-6(IL-6)were the core targets of anti-inflammatory effects of matrine.GO functional enrichment analysis showed that the target involved 62 biological processes(BP),16 cellular components(CC)and 12 molecular functions(MF).A total of 71 signaling pathways were obtained by KEGG pathway enrichment analysis.The molecular docking prediction results showed that matrine stably bound to the key core targets and had a good interaction with them.In this study,network pharmacology and molecular docking technology were used to reveal the mechanism of the anti-inflammatory effect of matrine through multiple targets and multiple pathways,which provides a reference for further clinical application of matrine in dairy cow production.