基于网络药理学和分子对接探究诃子鞣酸防治奶牛子宫内膜炎的作用机制

doi:10.16431/j.cnki.1671-7236.2023.04.034

摘要/Abstract

摘要： 【目的】基于网络药理学结合分子对接技术探究诃子鞣酸防治奶牛子宫内膜炎的作用,并阐明其潜在机制。【方法】通过SwissTargetPrediction和PharmMapper数据库收集和预测诃子鞣酸的作用靶点,通过UniProt数据库标准化并去重。从OMIM和DRUGBANK数据库中获取奶牛子宫内膜炎相关基因并去重,绘制Venn图获取诃子鞣酸和奶牛子宫内膜炎交集靶点。使用STRING数据库构建蛋白-蛋白相互作用(PPI)网络,使用DAVID数据库进行GO功能和KEGG通路富集分析。利用分子对接技术对KEGG通路富集分析后得到的关键通路靶点进行分子对接,以验证网络药理学分析结果的准确性。【结果】通过多个数据库检索及筛选获得诃子鞣酸潜在靶点基因333个,奶牛子宫内膜炎相关靶点基因342个,共有18个交集靶点。PPI结果显示,诃子鞣酸可能作用于前列腺素-内过氧化物酶合酶1(prostaglandin G/H synthase 1,PTGS1)、PTGS2、花生四烯酸12-脂氧合酶(arachidonate 12-lipoxygenase,ALOX12)、ALOX15等18个关键靶点。GO功能和KEGG通路富集分析结果显示,诃子鞣酸可通过脂氧合酶途径、花生四烯酸代谢通路、雌激素信号等通路防治奶牛子宫内膜炎。分子对接结果显示,诃子鞣酸与所得关键靶点均具有良好的结合活性,诃子鞣酸可通过多靶点发挥防治奶牛子宫内膜炎的作用,证明网络药理学预测结果准确。【结论】诃子鞣酸可能通过与PTGS1、PTGS2、ALOX12、细胞肿瘤抗原p53(cellular tumor antigen p53,TP53)结合,在脂氧合酶通路、花生四烯酸代谢过程上发挥防治奶牛子宫内膜炎的作用。

关键词: 诃子鞣酸; 奶牛子宫内膜炎; 网络药理学; 靶点; 分子对接

Abstract: 【Objective】 Based on network pharmacology and molecular docking technology,this paper explored the role of chebulagic acid in preventing and treating cow endometritis,and clarified its potential mechanism.【Method】 The action targets of chebulagic acid were collected and predict through SwissTargetPrediction and PharmMapper databases,and standardized and de-duplicated through UniProt database.Cow endometritis related genes were acquire from OMIM and DRUGBANK databases and de-duplicated.Venn map was drawn to obtain the intersection target of chebulagic acid and cow endometritis.The protein-protein interaction (PPI) network was constructed using STRING database,and the GO function and KEGG pathway enrichment analysis were performed using DAVID database.The molecular docking technology was used to dock the key pathway targets obtained after enrichment analysis of KEGG pathway to verify the accuracy of network pharmacological analysis results.【Result】 333 potential target genes of chebulagic acid and 342 target genes related to cow endometritis were obtained by searching and screening multiple databases,with a total of 18 overlapping targets.PPI results showed that chebulagic acid might act on 18 key targets,such as prostaglandin G/H synthase 1(PTGS1),PTGS2,arachidonate 12-lipoxygenase (ALOX12),ALOX15,etc.. The results of GO founction and KEGG pathway enrichment analysis showed that chebulagic acid could prevent and treat cow endometritis through lipoxygenase pathway,arachidonic acid metabolism pathway,estrogen signal pathway,etc.Molecular docking results showed that chebulagic acid had good connectivity with the key targets obtained,which could play a role in preventing and treating cow endometritis through multiple targets,proving that the network pharmacological prediction results were accurate.【Conclusion】 Chebulagic acid might play a role in preventing and treating cow endometritis by combining with PTGS1,PTGS2,ALOX12 and cellular tumor antigen p53 (TP53) in the lipoxygenase pathway and arachidonic acid metabolism process.

Key words: chebulagic acid; endometritis; network pharmacology; targets; molecular docking

中图分类号:

S859.7

刘鑫煜, 崔强, 张兰欣, 范佺荣, 李政忆, 高瑞峰. 基于网络药理学和分子对接探究诃子鞣酸防治奶牛子宫内膜炎的作用机制[J]. 中国畜牧兽医, 2023, 50(4): 1632-1641.

LIU Xinyu, CUI Qiang, ZHANG Lanxin, FAN Quanrong, LI Zhengyi, GAO Ruifeng. Study on Mechanism of Chebulagic Acid in Treatment of Cow Endometritis Based on Network Pharmacology and Molecular Docking[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(4): 1632-1641.

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