基于网络药理学和分子对接探究山楂调节氧化应激的作用机制

doi:10.16431/j.cnki.1671-7236.2023.01.041

摘要/Abstract

摘要： 【目的】运用网络药理学和分子对接方法研究山楂调节氧化应激的活性成分及潜在作用机制。【方法】通过TCMSP数据库检索山楂的化学成分及其作用靶点；在Uniprot数据库中对所得靶点进行标准基因名转化。利用GeneCards和OMIM数据库筛选氧化应激相关靶点。通过Venny 2.1.0软件获得山楂和氧化应激的交集靶点；借助STRING数据库和Cytoscape 3.8.0软件构建山楂-主要活性成分-靶点网络和蛋白-蛋白互作网络，筛选核心靶点，随后利用AutoDockTools 1.5.7和AutoDock Vina 1.1.2软件进行分子对接。应用DAVID数据库进行GO功能富集和KEGG通路注释分析，结果由Pymol软件进行可视化作图。【结果】筛选获得槲皮素、山奈酚、异鼠李素、豆甾醇、谷甾醇、表儿茶素等山楂的主要活性成分。基于主要活性成分和氧化应激分别筛选获得185和9 647个靶点，其中山楂与氧化应激交集靶点共171个，如丝氨酸/苏氨酸蛋白激酶AKT （serine/threonine-protein kinase AKT，AKT1）、细胞肿瘤抗原p53（cellular tumor antigen p53，TP53）、肿瘤坏死因子（tumor necrosis factor，TNF）、白细胞介素6（interleukin 6，IL6）、血红素加氧酶1（heme oxygenase 1，HMOX1）、髓过氧化物酶（myeloperoxidase，MPO）、醌氧化还原酶1（NAD （P） H：quinone oxidoreductase，NQO1）等。分子对接结果显示，山楂的6个主要活性成分与筛选靶点具有较好的结合活性，其中NQO1与豆甾醇、谷甾醇，AKT1与槲皮素、山奈酚、表儿茶素结合活性最好。GO功能富集筛选出987条目，其中生物过程主要包括RNA聚合酶Ⅱ启动子的转录正调控、细胞因子介导信号通路、正调控转录DNA模板化等。通过KEGG通路注释得到177条信号通路，包括TNF、IL17、丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）等信号通路。【结论】本研究初步揭示了山楂可通过多成分、多靶点、多通路调节机体氧化应激，为进一步研究山楂精准抗氧化的作用机制提供了科学依据。

关键词: 山楂; 网络药理学; 分子对接; 氧化应激; 作用机制

Abstract: 【Objective】 The purpose of the experiment was to study the active components and potential mechanism of hawthorn in regulating oxidative stress by using network pharmacology and molecular docking methods.【Method】 The active chemical ingredients and potential targets of hawthorn were screened by TCMSP database, and the potential targets were standardized in Uniprot database.Targets related to oxidative stress were screened out by GeneCards and OMIM databases.The overlapping targets of hawthorn and oxidative stress were gained via Venny 2.1.0.STRING database and Cytoscape 3.8.0 software were used to construct the hawthorn-main active ingredients-target network and protein-protein interaction (PPI) network to screen the core targets.AutoDocks Tools 1.5.7 and AutoDock Vina 1.1.2 were used to perform molecular docking.DAVID database was used for GO function enrichment analysis and KEGG pathway annotation.【Result】 Active ingredients of hawthorn were screened, including quercetin, kaempferol, isorhamnetin, stigmasterol, sitosterol, and ent-epicatechin.185 and 9 647 potential targets were identified respectively based on the main active ingredients of hawthorn and oxidative stress.A total of 171 overlapping targets of hawthorn and oxidative stress were screened, including AKT1, TP53, TNF, IL6, HMOX1, MPO, NQO1, et al.The results of molecular docking showed that the 6 active ingredients of hawthorn showed high binding activity with these targets, with NQO1 to stigmasterol and sitosterol, and AKT1 to quercetin, kaempferol and epicatechin being the most.GO function analysis showed that the prevention of oxidative stress by hawthorn involved 987 items, biological processes mainly included positive regulation of transcription from RNA polymeraseⅡ promoter, cytokine-mediated signaling pathway, positive regulation of transcription DNA-templated.While KEGG annotation identified several signal pathways, including TNF, IL17 and MAPK.【Conclusion】 This study revealed that hawthorn might regulate oxidative through multiple ingredients, targets and pathways, which would provide a scientific basis for analyzing the precious anti-oxidative mechanism.

Key words: hawthorn; network pharmacology; molecular docking; oxidative stress; mechanism

中图分类号:

S853.74

张祖烽, 张宇欣, 孙悦龙, 郑威, 李秀梅. 基于网络药理学和分子对接探究山楂调节氧化应激的作用机制[J]. 中国畜牧兽医, 2023, 50(1): 408-420.

ZHANG Zufeng, ZHANG Yuxin, SUN Yuelong, ZHENG Wei, LI Xiumei. Study on Mechanism of Hawthorn in Regulating Oxidative Stress Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(1): 408-420.

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