基于网络药理学和分子对接研究青果-槐花药对抗幽门螺杆菌感染的活性成分和作用机制

Active Components and Mechanism of Canarii Fructus-Sophorae Flos on Inhibition of Helicobacter Pylori Infection Based on Network Pharmacology and Molecular Docking

关键词:  青果  槐花  幽门螺杆菌  网络药理学  分子对接  活性验证

Key words:  Canarii Fructus  Sophorae Flos  Helicobacter pylori  network pharmacology  molecular docking  antibacterial activity verification

摘要:

目的 基于网络药理学和分子对接的方法研究青果-槐花药对抗幽门螺杆菌(Helicobacter pylori,Hp)感染可能的活性成分和作用机制。方法 利用TCMSP数据库及文献检索获取青果、槐花的活性成分,TCMSP、BATMAN-TCM、SwissTargetPrediction数据库获取成分靶标。通过Genecards、Drugbank和DisGeNET数据库收集与Hp感染相关的靶标,并与成分靶标相比较,筛选出潜在靶标。利用STRING数据库获取潜在靶标之间的相互关系,筛选出核心靶标。在DAVID数据库中进行潜在靶标的GO分类富集分析和KEGG通路富集分析。通过Autodock进行核心靶标与活性成分的分子对接。最后用体外抗菌试验验证青果-槐花的抗菌活性。结果 共收集到青果-槐花药对的20个主要活性成分,通过调节154个潜在靶标参与疾病过程,涉及TNF、FoxO、Toll样受体等通路的作用。活性成分中槲皮素、染料木素、山柰酚、鞣花酸与核心靶标具有良好的结合能力,可能通过作用于TP53、AKT1、IL6等靶标,干扰Hp的侵入和定植。青果-槐花药对抗Hp活性强于单药,其最小抑菌浓度为1.25 mg·mL^-1。结论 本研究探索了青果-槐花药对抗Hp感染可能的活性成分、靶标和通路,其作用机制复杂多样,符合中医药治疗疾病的多成分、多靶点、多途径的作用特点,为青果-槐花药对治疗Hp感染提供了理论依据。

Abstract:

OBJECTIVE To explore active components and mechanism of Canarii Fructus-Sophorae Flos on inhibition of Helicobacter pylori(Hp) infection based on network pharmacology and molecular docking. METHODS The active components of Canarii Fructus-Sophorae Flos were obtained from TCMSP platform and literature search. TCMSP, BATMAN-TCM and SwissTargetPrediction databases were used to obtain the targets of components. Targets related to Hp infection were collected from Genecards, Drugbank and DisGeNET databases. The common targets of active components and disease were selected to be potential targets. STRING database was used to obtain an interaction map of potential targets, based on which the key targets were selected. The GO classified enrichment analysis and the KEGG pathway enrichment analysis were performed in DAVID database. Molecular docking between the active components and the key targets was carried out by Autodock. Finally, the antibacterial activity of Canarii Fructus-Sophorae Flos was verified by in vitro antibacterial test. RESULTS Twenty active components of Canarii Fructus-Sophorae Flos were collected, which were involved in the disease process by regulating 154 potential targets and signal pathways including TNF, FoxO, Toll-like receptor signal pathways. The quercetin, genistein, kaempferol and ellagic acid among the active components showed good binding ability with the key targets, suggesting that they may interfere with the invasion and colonization of Hp by acting on TP53, AKT1, IL6 and other targets.The anti-Hp activity of Canarii Fructus-Sophorae Flos was better than those of single drugs, with the minimum inhibitory concentration of 1.25 mg·mL^-1.CONCLUSION This study preliminarily explore the active components, potential targets and pathways of Canarii Fructus-Sophorae Flos on inhibition of Hp infection. Its complex and diverse mechanism conforms to the characteristic of traditional Chinese medicine in the treatment of disease, which is multi-components, multi-targets and multi-pathways. The results provide theoretical basis for the treatment of Hp infection by Canarii Fructus- Sophorae Flos. KEYWORDS:Canarii Fructus; Sophorae Flos; Helicobacter pylori; network pharmacology; molecular docking; antibacterial activity