基于UPLC-Q/TOF-MS与网络药理学探究解语丹治疗中风的活性成分及作用机制

目的:探究解语丹治疗中风的主要活性成分及其作用机制。方法:采用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q/TOF-MS)分析解语丹的化学成分,并借助UNIFI数据库和文献进行结构鉴定。借助SwissADME网站对成分进行代谢参数筛选后,使用Swiss Target Prediction网站预测筛选成分的靶点为解语丹的药物靶点。挖掘GeneCards数据库和NCBI数据库的中风相关疾病靶点。Venny网站取得解语丹治疗中风的靶点。STRING数据库和Cytoscape软件挖掘高置信度作用靶点。R软件对靶点进行GO(基因本体)功能和KEGG通路的富集分析,并构建“药物-成分-靶点-通路-疾病”网络图。结果:共检测出解语丹化学成分102种,包括氨基酸、寡糖类、香豆素类、山酮类、环烯醚萜类、黄酮类、皂苷类、有机酸和生物碱等,筛选分析得到48种活性成分和562个药物靶点,与疾病靶点取交集得97个药物与疾病的共同靶点。STRING得65个高置信度靶点,富集分析得到3209个GO功能进程和190条通路,GO进程主要涉及创口与炎症、血管管径变化及血压调节等GO生物过程类、细胞粘着和细胞凝聚等GO细胞组成类、肽类激素内切酶活性及血红蛋白等GO分子功能类。KEGG通路主要有花生四烯酸代谢、补体和凝血级联、血小板激活流体剪切应力和动脉粥样硬化、脂质和动脉粥样硬化等脂质代谢、凝血功能、动脉粥样硬化等与中风密切相关的通路。结论:解语丹可能是以调节脂质代谢与凝血功能、改善粥样硬化等途径治疗中风,表明解语丹通过多成分介导多靶点,作用于多进程和多通路协同治疗中风的特点。

Study on active components and mechanism of Jieyudan Decoction in the treatment of stroke based on network pharmacology and UPLC-Q/TOF-MS

OBJECTIVE To explorethe main active components of Jieyudan and its the mechanismin the treatment of Stroke.METHODS The chemical components of Jieyudan were characterized by combination of UPLC-Q/TOF-MS,UNIFI database and literature.After screening the metabolic parameters,Swiss Target Prediction wasperformed to predict the targets of Jieyudan.Stroke related disease targets were mined from GeneCards database and NCBI database.The targets for the treatment of stroke were represented by a Venn diagram.The combination of STRING database and the Cytoscape software were used to find high confidence targets.R software was used for enrichment analysis of GO function and KEGG Pathway,then construct the network diagram of "drug-component-target-pathway-disease".RESULTS A total of 102 chemical components were detected,include amino acids,oligosaccharides,coumarins,xanthones,iridoids,flavonoids,saponins,organic acids and alkaloids,etc.,48 active components and 562 drug targets were obtained,among of which,drugs and diseases have 97 common targets.65 relevant targets with high confidence were obtained by STRING.3209 GO functional processes and 190 pathways were obtained by GO functional enrichment analysis and KEGG enrichment analysis,GO process mainly involves GO biological processes such as wound and inflammation,vascular diameter change and blood pressure regulation,GO cell components such as cell adhesion and cell aggregation,peptide hormone endonuclease activity and GO molecular components such as hemoglobin.KEGG pathway mainly includes arachidonic acid metabolism,complement and coagulation cascade,platelet activation fluid shear stress and atherosclerosis,lipid metabolism and atherosclerosis,coagulation function,atherosclerosis and other pathways closely related to stroke.CONCLUSION Jieyudan may treat stroke by regulating lipid metabolism and coagulation function,attenuating atherosclerosis and other approaches,indicating that Jieyudan acts on multiple processes and pathways in synergistic treatment of stroke through multi-component mediating multi-target.