摘要
目的:基于网络药理学预测石榴皮抗甲型流感的潜在有效靶点及作用机制,并通过动物实验进行验证。方法:通过TCMSP技术平台检索石榴皮的有效成分,筛选其作用的靶标。甲型流感的靶标通过TTD、DRUGBANK等数据库筛选。利用Cytoscape绘制石榴皮抗甲型流感网络图,通过STRING数据库构建蛋白互作网络,并对关键靶标的生物功能进行注释与通路分析。甲型流感病毒感染小鼠,使用酶联免疫吸附试验(ELISA)、蛋白质印迹法(Western blot)检测白细胞介素17(interleukin 17,IL-17)通路中关键蛋白、炎症因子的表达,观测小鼠体质量、肺指数变化。结果:石榴皮中有7个潜在有效成分抗流感病毒、96个有效靶点,其中RELA、MAPK1、JUN、HIF1A、ESR1、NFKBIA、TP53可能为核心靶点,其作用机制可能与IL-17信号通路、化学致癌-受体激活、磷脂酰肌醇3-激酶等通路有关。初步的动物实验显示,石榴皮提取物参与调控IL-17通路,抑制炎症因子白细胞介素6(interleukin 6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素1β(interleukin 1β,IL-1β)、TRAF6(TNF receptor associated factor 6)及核因子κB(nuclear factor kappa-B,NF-κB)p65蛋白表达(P<0.05)。结论:通过预测得出石榴皮中所含的6个成分与不同靶点、通路交互作用,抑制多个炎症因子相关蛋白的表达,进而防治甲型流感。
Objective:To explore the potential effective targets and mechanism of Punica granatum L.against influenza based on network pharmacology and verify them with animal model.Methods:The active components in Punica granatum L.were retrieved by Chinese Medicine System Pharmacology Platform(TCMSP),and active targets were screened.The Cytoscape software was used to construct network of Punica granatum L.for influenza treatment.The targets of influenza A were screened through databases such as TTD and DRUGBANK.STRING database was used to construct the network of influenza A,and the biological function annotation and pathway analysis of key targets were performed.Mice of experimental model were infected with influenza A.The expression of key proteins and inflammatory factors of IL-17 pathway was detected by ELISA and Western blot.The body weight and lung index of mice were detected.Results:There were 7 active components in Punica granatum L.against influenza A and 96 effective targets.Among them,RELA,MAPK1,JUN,HIF1A,ESR1,NFKBIA and TP53 genes may be the core targets.The possible mechanism of action may be related to IL-17 signaling pathway,chemical carcinogenic-receptor activation,phosphatidylinositol 3-kinase pathway,etc.Preliminary animal experiments showed that Punica granatum L.extracts were involved in the regulation of IL-17 pathway to inhibit the expression of inflammatory cytokines IL-6,TNF-α,IL-1βand TRAF6,NF-κB protein(P<0.05).Conclusion:There are 6 components contained in Punica granatum L.interacting with different targets and pathways to inhibit the expression of proteins of multiple inflammatory cytokines to inhibit influenza A.
作者
邢亚东
杨兵
丁琪
罗凯文
XING Yadong;YANG Bing;DING Qi;LUO Kaiwen(School of Pharmacy,Bengbu Medical College,Bengbu 233030,China;School of Pharmacy,Hebei University)
出处
《包头医学院学报》
CAS
2024年第1期13-20,共8页
Journal of Baotou Medical College
基金
安徽省自然科学项目(1908085QH376)
安徽省中医药传承创新科研项目(2020ccyb20)
2021年安徽省省级大学生创新创业训练计划项目(S202110367085)
蚌埠医学院自然科学重点项目(2021byzd034)
国家自然科学基金项目(21904005)。
