基于网络药理学和分子对接分析金银花缓解牛氧化应激的分子机制

doi:10.16431/j.cnki.1671-7236.2023.08.037

摘要/Abstract

摘要： 【目的】分析预测金银花缓解牛氧化应激的潜在活性成分和靶点,探讨其可能的作用机理。【方法】利用中药系统药理学分析平台(TCMSP)和文献查找的方式搜集金银花的活性成分,使用TCMSP和SwissTargetPrediction数据库查找活性成分对应的靶点,在NCBI数据库的Gene平台收集牛氧化应激相关基因。使用STRING数据库和Cytoscape 3.8.2软件构建并分析金银花与牛氧化应激蛋白-蛋白相互作用网络。利用DAVID数据库对交集靶点进行GO功能和KEGG通路富集分析。通过AutoDock软件进行分子对接验证关键活性成分与核心靶点的结合活性。【结果】共获得37个金银花有效活性成分,涉及37个与牛氧化应激相关的靶点。其中槲皮素、山柰酚、木犀草素、芦丁、金圣草黄素等为金银花缓解牛氧化应激的关键活性成分,肿瘤坏死因子(TNF)、前列腺素内过氧化物合酶2(PTGS2)、β-连环蛋白(CTNNB1)、血清白蛋白(ALB)、半胱氨酸天冬氨酸蛋白酶-3(CASP3)、过氧化氢酶(CAT)、肿瘤蛋白p53(TP53)等为金银花缓解牛氧化应激的核心靶点。GO功能和KEGG通路富集分析显示,靶点的作用涉及生物过程、细胞组分和分子功能3个方面,并参与到缺氧诱导因子1信号通路、过氧物酶体、MAPK信号通路等多条代谢通路。分子对接结果验证了金银花的关键活性成分槲皮素、山柰酚、木犀草素与核心靶点TNF、PTGS2、CTNNB1、ALB、CASP3、CAT、TP53均有较好的结合活性。【结论】本研究结果揭示了金银花缓解牛氧化应激的潜在活性成分为槲皮素、山柰酚、木犀草素等,作用靶点为TNF、PTGS2、CTNNB1等,为金银花作为功能性饲料添加剂的开发和后续研究提供理论参考。

关键词: 金银花; 牛; 氧化应激; 网络药理学; 分子对接

Abstract: 【Objective】 The aim of this study was to analyze and predict the potential active ingredients and targets of Lonicerae Japonicae Flos to alleviate oxidative stress in cattle and explore its possible mechanism of action.【Method】 The active ingredients of Lonicerae Japonicae Flos were collected using Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and literature search,and the targets corresponding to the active ingredients were identified using TCMSP and SwissTargetPrediction databases,and oxidative stress in cattle-related genes were collected in the gene platform of the NCBI database.The STRING database and Cytoscape 3.8.2 software were used to construct and analyze the protein-protein interaction network of Lonicerae Japonicae Flos and oxidative stress in cattle.GO function and KEGG pathway enrichment analysis of the intersection targets were performed using the DAVID database.Molecular docking was performed by AutoDock software to verify the binding activity of key active ingredients to the core targets.【Result】 There were 37 active ingredients of Lonicerae Japonicae Flos,which were involved in 37 targets related to oxidative stress in cattle.Among them,quercetin,kaempferol,luteolin,rutin and chryseriol were the key active ingredients of Lonicerae Japonicae Flos to alleviate oxidative stress in cattle,and tumor necrosis factor (TNF),prostaglandin-endoperoxide synthase 2 (PTGS2),catenin beta-1 (CTNNB1),serum albumin (ALB),caspase 3 (CASP3),catalase (CAT) and tumor protein p53 (TP53) were the core targets to alleviate oxidative stress in cattle.GO functional enrichment and KEGG pathway analysis showed that the targets were involved in biological process, cell component and molecular function,and were involved in multiple metabolic pathways such as HIF-1 signaling pathway,peroxisome,and MAPK signaling pathway.Molecular docking confirmed that quercetin,kaempferol and luteolin,the key active ingredients of honeysuckle,have good binding activities to the common core targets TNF,PTGS2,CTNNB1,ALB,CASP3,CAT and TP53.【Conclusion】 The results of the study revealed the potential active ingredients of Lonicerae Japonicae Flos to alleviate oxidative stress in cattle were quercetin,kaempferol,luteolin,etc.,and the potential action targets were TNF,PTGS2,CTNNB1,etc.,providing theoretical references for the development and subsequent research of Lonicerae Japonicae Flos as a functional feed additive.

Key words: Lonicerae Japonicae Flos; cattle; oxidative stress; network pharmacology; molecular docking

中图分类号:

S853.74

刘魏魏, 张宇欣, 周炜炜, 戴小枫, 付弘赟, 雒文捷, 李秀梅. 基于网络药理学和分子对接分析金银花缓解牛氧化应激的分子机制[J]. 中国畜牧兽医, 2023, 50(8): 3391-3402.

LIU Weiwei, ZHANG Yuxin, ZHOU Weiwei, DAI Xiaofeng, FU Hongyun, LUO Wenjie, LI Xiumei. Mechanism of Lonicerae Japonicae Flos Alleviating Oxidative Stress in Cattle Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(8): 3391-3402.

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