基于UPLC-QE-MS联合网络药理学研究地板藤治疗原发性痛经的作用机制

Mechanism of Dibanteng in the treatment of primary dysmenorrhea based on UPLC-QE-MS and network pharmacology

目的:基于UPLC-QE-MS分析地板藤化学成分以及通过网络药理学探讨地板藤治疗原发性痛经的作用机制。方法:通过UPLC-QE-MS分析所得地板藤化学成分,利用Swiss ADME和Swiss Target Prediction筛选出药物化学成分相应靶点,再通过GeneCards、OMIM、Drugbank等数据库得到原发性痛经疾病靶点,利用Cytoscape绘出“药物-成分-靶点”及蛋白质与蛋白质相互作用(PPI)图。其次可由Metascape与微生信得到GO与KEGG富集分析可视化图,最后使用分子对接对网络药理学内容进行初步验证。结果:经UPLC-QE-MS共分析出117个化合物,通过Swiss ADME筛选的出79个成分,这些成分作用于362个靶点;药物-疾病共有靶点30个,经PPI网络图得可能作用的靶点为白蛋白(ALB)、前列腺素-过氧化内合酶2(PTGS2)、过氧化物酶体增殖物激活受体α(PPARA);经GO富集分析得312条,主要涉及脂肪酸代谢过程、花生四烯酸代谢过程、异生代谢过程、血红素结合过程、类固醇羟化酶活性过程等;KEGG富集分析得花生四烯酸代谢、PPAR、AMPK、cAMP、PI3K-Akt等26条通路;分子对接结果显示关键靶点与活性成分结合结合效能较低,具较好的亲和力。结论:初步分析得出地板藤的化学成分,同时探讨了其治疗原发性痛经可能的药效物质及其作用机制,后续为其治疗原发性痛经提供理论依据。

OBJECTIVE To analyze the chemical constituents of Dibanteng based on UPLC-QE-MS,and to explore the mechanism of Dibanteng in the treatment of primary dysmenorrhea by network pharmacology.METHODS Dibanteng chemistries were obtained by UPLC-QE-MS analysis,and the corresponding target of drug chemical components were screened by Swiss Target Prediction.The targets of primary dysmenorrhea disease were obtained by GeneCards,OMIM,Drugbank and other databases.Cytoscape was used to draw the"drug-composition-target"and protein-protein interaction(PPI)diagram.Metascape and Bioinformatics were used to obtain visualization of GO and KEGG enrichment analysis,and finally,molecular docking was used to verify the network pharmacology.RESULTS A total of 117 compounds were analyzed by UPLC-QE-MS,and a total of 79 components were selected by Swiss ADME,which acted on 362 targets;a total of 30 drug-disease targets were screened,and PPI network showed that the possible targets were albumin(ALB),prostaglandin-endoperoxide synthase 2(PTGS2),and peroxisome proliferator activated receptor alpha(PPARA),etc.After GO enrichment analysis,312 samples were obtained,which mainly involved fatty acid metabolism,arachidonic acid metabolism,allogenic metabolism,heme binding,and steroid hydroxylase activity,etc.Totally 26 pathways including arachidonic acid metabolism,PPAR,AMPK,cAMP and PI3K-Akt were identified by KEGG enrichment analysis.The results of molecular docking suggested that the key target and the active ingredient had low binding efficiency.CONCLUSION The chemical composition of Dibanteng was obtained by preliminary analysis,and the possible pharmacodynamic substances and action mechanism of Dibanteng in the treatment of primary dysmenorrhea were discussed,which provide theoretical basis for the treatment of primary dysmenorrhea.