基于网络药理学研究石榴皮抗菌作用机制

Study on the Antibacterial Mechanism of Pomegranate Peel Based on Network Pharmacology

关键词:  网络药理学  石榴皮  抗菌  最小抑菌浓度

Key words:  network pharmacology  pomegranate peel  antibacterial  minimum bacteriostatic concentration

摘要:

目的 运用网络药理学和分子对接法探讨石榴皮抗菌作用机制。方法 利用网络药理学和分子对接分析石榴皮主要成分与抗菌靶点的关系，并研究石榴皮主要成分对大肠杆菌和金黄色葡萄球菌的最小抑菌浓度以及对碱性磷酸酶、核酸和蛋白质调控。结果 通过网络药理学筛选到石榴皮有8个成分与大肠杆菌43个蛋白存在相互作用，有5个成分与金黄色葡萄球菌27个蛋白存在相互作用。筛选到5个具有抑制大肠杆菌和金黄色葡萄球菌活性的主要成分，分别为槲皮素、鞣花酸、儿茶素、木犀草素、山奈酚。并且发现这5种成分处理大肠杆菌和金黄色葡萄球菌后，培养液上清中检测到较多碱性磷酸酶、核酸和蛋白质，表明这些成分通过破坏细菌细胞壁和细胞膜来发挥抑菌效果。共沉淀试验证明石榴皮主要成分没食子酸通过结合大肠杆菌和金黄色葡萄球菌中ndk蛋白和gnd蛋白来发挥抑菌作用。结论 本研究基于网络药理学和分子对接推测了石榴皮抗菌具有多成分-多靶点-多途径的特点，为进一步研究石榴皮抗菌的分子机制提供新思路和新方向。

Abstract:

OBJECTIVE To explore the antibacterial mechanism of pomegranate peel using network pharmacology and molecular docking method.METHODS The network pharmacology and molecular docking were used to analyze the relationship between main components of pomegranate skin and antibacterial targets, and studied the minimum inhibitory concentration of main components of pomegranate skin on Escherichia coli and Staphylococcus aureus, as well as the regulation of alkaline phosphatase, nucleic acid and protein.RESULTS Eight components of pomegranate skin interacted with 43 proteins of E. coli and 5 components interacted with 27 proteins of S. aureus through network pharmacology screening. Five main components, quercetin, ellagic acid, catechin, luteolin and kaempferol, were selected to inhibit the activity of E. coli and S. aureus. Moreover, it was found that more alkaline phosphatase, nucleic acid and protein were detected in the supernatant of the culture medium after the treatment of E. coli and S. aureus with these five ingredients, indicating that these components would destroy the cell wall and cell membrane of the bacteria, thus exerting bacteriostatic effect. The gallic acid, a main component of pomegranate skin, could bind nkd and gnd protein in E. coli and S. aureus to play an antibacterial effect through coprecipitation assay.CONCLUSION Based on network pharmacology and molecular docking, this study speculated that pomegranate peel has the characteristics of multi-component, multi-target and multi-pathway in antibacterial action, providing new ideas and new directions for further research on the molecular mechanism of pomegranate peel antibacterial activity.