[关键词]
[摘要]
目的 运用网络药理学的方法来研讨麦门冬汤治疗肺纤维化(Pulmonary fibrosis,PF)的作用机制。方法 利用数据库分别筛选麦门冬汤各药材的活性成分及对应的靶点,并获得肺纤维化相关的治疗靶点,提取成分与疾病的交集靶点;构建“成分-靶点-通路”网络,对靶点进行KEGG(Kyoto Encyclopedia of Genes and Genomes)通路富集和GO(Gene Ontology)生物功能分析,进一步对度值评分较高的分子及靶点进行分子对接分析,评估成分与靶点的结合活性。结果 筛选得到麦门冬汤有145个活性成分,疾病与活性成分共有靶点704个,网络分析结果显示麦门冬汤活性成分涉及血管内皮生长因子、信号转导与转录激活因子3、半胱氨酸蛋白酶3、酪氨酸受体激酶SRC等相关的50个蛋白靶点,药物可通过影响多种细胞分化及生物酶活性来调节AGE-RAGE信号通路、癌症信号通路及人类巨细胞病毒感染等信号通路从而发挥治疗肺纤维化的作用,分子对接结果显示β-谷甾醇、豆甾醇、山奈酚、原阿片碱、白桦脂酸、槲皮素化合物与靶点AKT1、GAPDH、STAT3、MAPK3有较低的结合能,表明以上小分子具有潜在的抑制肺纤维化活性;体外实验表明麦门冬汤可促进MRC-5人胚肺成纤维细胞中AKT1、p-AKT蛋白表达,下调VEGF蛋白。结论 麦门冬汤治疗肺纤维化的作用具有多成分-多靶点-多途径的特点,该研究可为麦门冬汤的现代化研究提供新的研究思路和方向。
[Key word]
[Abstract]
Objective To study the mechanism of Maimendong Decoction in ttreating pulmonary fibrosis by network pharmacology.Methods The database was used to screen the active ingredients and corresponding targets of each medicinal material of Maimendong Decoction, and obtain the relevant therapeutic targets of pulmonary fibrosis, to extract the intersection targets between the ingredients and the disease; construct the ingredient-target-pathway network. The target is subjected to the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment and GO (Gene Ontology) biological function analysis, and further molecular docking analysis is performed on the molecules and targets with higher degree scores to evaluate the binding activity of the components and the target.Results There were 145 active ingredients in Maimendong decoctiond and 704 targets for diseases and active ingredients. There are 50 protein targets were discriminated by the network analysis including vascular endothelial growth factor, serine-threonine protein kinase, cysteine protease 3, tyrosine receptor kinase SRC. Drugs can regulate the AGE-RAGE signaling pathway, cancer signaling pathway and human cytomegalovirus infection signaling pathway by affecting a variety of cell differentiation and biological enzyme activity to play a role in the treatment of pulmonary fibrosis. The results of molecular docking showed that β-sitosterol, stigmasterol, kaempferol,fumarine, mairin, quercetin and other compounds had low binding energy with the target AKT1、GAPDH、STAT3、MAPK3, indicating that the above small molecules have potential inhibitory activity against pulmonary fibrosis. In vitro experiments show that Maimendong Decoction can promote AKT1 and p-AKT protein in MRC-5 human embryonic lung fibroblasts and down-regulate VEGF protein.Conclusion The study shows the characteristics of multi-component, multi-target and multi-pathway of Maimendong decoction, It provides a new idea and direction for the further study of the mechanism of Maimendong decoction in the treatment of pulmonary fibrosis.
[中图分类号]
R-058
[基金项目]
西藏藏医药大学博士点建设及中药学博士点培育项目(BSDJS2022007):基于数据挖掘探讨藏医治疗“查隆病”的用药规律研究,负责人:格知加;2021年西藏藏医药大学中药学(藏药)博士点培育科研支撑计划项目(BSDPY-21-12):藏药龙胆花类和绿绒蒿类花粉粒电镜微形态特征研究,负责人:索郎拉宗。西藏藏医药大学“十四五”科研项目(2022ZYYGH03),负责人:仁青加。