摘要
为初步明确厚朴酚药-药共晶缓解急性肺损伤(ALI)的作用机制,本试验利用PubChem数据库和Swiss Target Prediction化合物相关靶点在线预测平台筛选并提取厚朴酚(MAG)、川芎嗪(TMP)、甜菜碱(BTN)和烟酰胺(NIC)的靶点;结合GeneCards数据库获取ALI相关的疾病靶点;利用Venny 2.1.0构建可视化韦恩图以明确两者的交集靶点;基于STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并采用Cytoscape 3.9.1软件进行网络拓扑特性分析,筛选核心作用节点;通过DAVID数据库对交集靶点进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析,并通过CBDock2平台完成分子对接验证。结果显示,厚朴酚药-药共晶靶向AKT丝氨酸/苏氨酸激酶1(AKT1)、表皮生长因子受体(EGFR)、糖原合酶激酶3β(GSK3β)、哺乳动物雷帕霉素靶蛋白(MTOR)、丝裂原活化蛋白激酶14(MAPK14)等炎症和细胞凋亡通路核心靶点;GO分析显示,其主要涉及对外源性刺激的反应和蛋白质磷酸化功能;KEGG通路富集分析显示,其通过钙信号和Ras相关蛋白1等多条信号通路发挥作用;分子对接验证显示,MAG、TMP和NIC与AKT1、EGFR等核心靶点结合稳定(结合能<-4 kcal/mol)。结果表明,厚朴酚药-药共晶通过多靶点和多通路协调缓解ALI,为后续动物试验提供理论依据。
To preliminarily elucidate the mechanism by which the magnolol drug-drug cocrystal alleviates acute lung injury(ALI),this study utilized the PubChem database and the Swiss Target Prediction online platform to predict and extract the targets of magnolol(MAG),tetramethylpyrazine(TMP),betaine(BTN),and nicotinamide(NIC).ALI-related disease targets were retrieved from the GeneCards database.Venny 2.1.0 was employed to create a visual Venn diagram to identify intersecting targets.A protein-protein interaction(PPI)network was constructed using the STRING database,and Cytoscape 3.9.1 software was used to perform network topology analysis to identify key functional nodes.Gene ontology(GO)enrichment and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses were conducted via the DAVID database,and molecular docking validation was performed using the CB-Dock2 platform.Results indicated that the magnolol drug-drug cocrystal targets key proteins involved in inflammatory and apoptotic signaling pathways,such as AKT serine/threonine kinase 1(AKT1),epidermal growth factor receptor(EGFR),glycogen synthase kinase 3 beta(GSK3β),mammalian target of rapamycin(MTOR),and mitogen-activated protein kinase 14(MAPK14).GO analysis revealed that these targets are primarily involved in responses to exogenous stimuli and protein phosphorylation.KEGG enrichment analysis showed that multiple pathways,including calcium signaling and Ras-related protein 1(Rap1)signaling,are implicated in the therapeutic effects.Molecular docking validation showed that MAG,TMP,and NIC form stable interactions with core targets such as AKT1 and EGFR(binding energy<–4 kcal/mol).These findings suggest that the magnolol drug-drug cocrystal alleviates ALI through multi-target and multi-pathway mechanisms,providing theoretical support for future animal experiments.
作者
刘梦歌
张娜
郭子明
张楠
何欣
赵兴华
LIU Mengge;ZHANG Na;GUO Ziming;ZHANG Nan;HE Xin;ZHAO Xinghua(College of Veterinary Medicine,College of Traditional Chinese Veterinary Medicine,Hebei Agricultural University,Baoding 071000,China)
出处
《中国兽医杂志》
北大核心
2025年第8期107-115,共9页
Chinese Journal of Veterinary Medicine
基金
国家重点研发计划资助(2023YFD1800804)
国家自然科学基金(32473073)。
关键词
厚朴酚药-药共晶
急性肺损伤
网络药理学
分子对接
作用机制
magnolol drug-drug cocrystal
acute lung injury
network pharmacology
molecular docking
mechanism of action
