金银花防治猪繁殖与呼吸综合征的潜在作用机制

Potential Mechanism of Honeysuckle Against Porcine Reproductive and Respiratory Syndrome

目的:采用网络药理学和分子对接技术揭示金银花防治猪繁殖与呼吸综合征(PRRS)的活性成分、靶点及作用机制。方法:中药系统药理学数据库与分析平台(TCMSP)筛选得到金银花的潜在活性成分及作用靶点,使用比较毒理基因组学数据库(CTD)收集PRRS疾病基因,映射后的交集靶点利用String构建蛋白互作网络,使用Cytoscape 3.7.2构建药物-成分-靶点-疾病网络图,通过Metascape对交集基因进行GO功能及KEGG通路富集分析,并对主要活性成分和关键蛋白进行了分子对接。结果:金银花28个活性成分的220个对应靶点,与PRRS疾病相关的744个基因映射,最终获得靶点70个。其中潜在活性成分有槲皮素、木犀草素、山奈酚等,关键抗PRRS蛋白是肿瘤坏死因子(TNF)、白介素6(IL6)、白蛋白(ALB)、胱天蛋白酶3(CASP3)、丝裂原活化蛋白激酶(MAPK14)等,GO和KEGG富集结果显示金银花主要调控病毒感染、炎症、氧化应激和免疫调节等通路发挥作用,分子对接结果也显示其主要活性成分与关键蛋白有较好的亲和作用。结论:金银花可能主要通过抑制炎症反应,调节免疫细胞因子和直接抗病毒感染等对PRRS发挥潜在的防治作用。

Objective:The network pharmacology and molecular docking were used to reveal the active components,target information and action process of honeysuckle against porcine reproductive and respiratory syndrome. Methods:The potential active ingredients and action targets of honeysuckle were obtained mainly from TCSMP(Traditional Chinese Medicine Systems Pharmacology),and the PRRS(porcine respiratory and reproductive syndrome)-related disease genes were collected by CTD(the Comparative Toxicogenomics Database). The protein protein interaction network was contructed by String,and the network of drug-component-target-disease was constructed with Cytoscape 3.7.2. GO(Gene Ontology)enrichment and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment analysis were conducted by Metascape,finally molecular docking of main active components and key proteins was conducted. Results:28 active components,220 corresponding targets and 744 genes related to PRRS disease were obtained,then 70 key targets were obtained by mapping. The potential active components include quercetin,luteolin,kaempferol,etc. The key targets are TNF(Tumor Necrosis Factor),IL6(Interleukin-6),ALB(Albumin),CASP3(Caspase 3),MAPK14(Mitogen-Activated Protein Kinase14),etc. The GO and KEGG enrichment results showed that honeysuckle mainly regulated signaling pathways including viral infection,inflammation,oxidative stress. The molecular docking results showed that the main active components had good affinity with key targets. Conclusion:Honeysuckle may play potential preventive and therapeutic effects on PRRS by inhibiting inflammatory response,regulating immune cytokines and direct antiviral infection.