网络药理学及分子对接法分析蒲公英-夏枯草治疗肉芽肿性乳腺炎的作用机制

Action mechanism of dandelion-prunella vulgaris in the treatment of granulomatous mastitis based on network pharmacology and molecular docking

目的运用网络药理学及分子对接技术探讨"蒲公英-夏枯草"药对治疗肉芽肿性乳腺炎(GLM)的分子作用机制。方法应用中药系统药理学数据库分析平台(TCMSP)、中药分子机制生物信息学分析工具(BATMAN-TCM)、文献检索等筛选蒲公英、夏枯草活性成分,通过Uniport、SwissTargetPrediction获取药物靶点,在GeneCards、OMIM、TTD疾病靶点数据库获取GLM靶点基因,筛选出药物、疾病交集靶点。利用Cytoscape软件绘制网络图,通过STRING平台及Cytoscape软件绘制靶点蛋白相互作用网络图,得到蒲公英、夏枯草治疗GLM的核心靶点。运用DAVID及Omicshare进行基因本体(GO)和京都基因与基因百科全书(KEGG)通路富集分析,应用Cytoscape绘制"靶点-通路"图。使用自动对接软件(Autoduck)将核心靶点与核心活性成分进行分子对接,通过分子绘图软件(PyMOL)将分子对接结果可视化。结果蒲公英-夏枯草药对活性成分34个,主要包括木犀草素、槲皮素、山柰酚、邻苯二甲酸丁酯,主要作用于IL-6、IL-1β、TNF等核心靶点,主要涉及Toll样受体、TNF、核苷酸结合寡聚结构域(NOD)样受体等信号通路,分子对接结果显示,核心活性成分与核心靶点具有良好的结合活性。结论蒲公英-夏枯草药对通过多成分、多靶点、多通路调控GLM免疫炎症。

Objective To investigate the molecular mechanism of “dandelion-prunella vulgaris” in the treatment of granulomatous mastitis(GLM) through network pharmacology and molecular docking technology. Methods The active components of dandelion and prunella vulgaris were screened by Traditional Chinese Medicine(TCM) Systems Pharmacology Database and Analysis Platform(TCMSP), a Bioinformatics Analysis Tool of Molecular Mechanism of TCM(BATMAN-TCM) and literature retrieval, obtained drug targets through Uniport and SwissTargetPrediction. GLM target genes were obtained from GeneCards, OMIM and TTD disease target databases, and drug and disease intersection targets were screened. The network diagram was drawn by Cytoscape software, and the target protein interaction network diagram was drawn by STRING platform and Cytoscape software to obtain the core targets of dandelion-prunella vulgaris in the treatment of GLM. DAVID and Omicshare were used for gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis, and Cytoscape was used to draw the “target pathway” map. The core target was docked with the core active ingredient by using the automated docking software(Autoduck), and the molecular docking results were visualized by the molecular mapping software(PyMOL). Results Dandelion-prunella vulgaris had 34 active components, mainly including luteolin, quercetin, kaempferol and butyl phthalate. It mainly acted on core targets such as IL-6, IL-1β and TNF, mainly involving Toll like receptors, TNF, nucleotide binding oligomerization domain(NOD) like receptors and other signal pathways. The molecular docking results showed that the core active components have good binding activity to the core targets. Conclusion The couplet medicines of dandelion-prunella vulgaris can regulate GLM immune inflammation through multi-component, multi-target and multi-channel.