摘要
目的:探究桃红四物汤促进骨折愈合的潜在药效物质及作用靶点和通路。方法:采用UPLC-Q-Exactive Orbitrap/MS技术,结合对照品比对与文献数据,对桃红四物汤化学成分进行鉴定。通过中药系统药理学数据库和分析平台(TCMSP)及SwissADME数据库,筛选活性成分。运用TCMSP数据库和SwissTargetPrediction数据库查找成分靶点;通过OMIM、Gene Cards数据库查找疾病靶点;采用String数据库和Cytoscape软件构建蛋白质相互作用网络;利用MetaScape数据库进行GO功能和KEGG通路富集分析;绘制与骨折愈合相关性大的通路的成分-靶点-通路图,通过网络节点度值筛选核心成分和关键靶点。使用AutoDockTools软件对桃红四物汤的核心成分与关键靶点进行分子对接验证。结果:质谱鉴别出桃红四物汤49个成分,主要为苯丙素、苯肽、苯乙醇苷、黄酮、萜、香豆素、有机酸类化合物。网络药理学预测出桃红四物汤促进骨折愈合的主要通路为AGE-RAGE、PI3K-Akt、EGFR、MAPK、IL-17通路,核心成分为槲皮素、没食子酸、咖啡酸、绿原酸、阿魏酸、苦杏仁苷、芍药苷、梓醇,关键靶点为PTGS2、MAPK1、EGFR、BCL2、VEGFA、CASP3、IL6、MMP2。分子对接结果显示,槲皮素、芍药苷、苦杏仁苷与PTGS2、IL6结合活性强。结论:桃红四物汤可通过多成分、多靶点、多通路的综合作用促进骨折愈合,该研究可为其临床应用奠定科学基础。
OBJECTIVE Explore the potential pharmacodynamic substances,targets and pathways of Taohong Siwu Decoction promoting fracture healing.METHODS Applying UPLC-Q-Exactive Orbitrap/MS technology,in comparison with reference sample and literature data,the chemical composition of Taohong Siwu Decoction was identified.Through retrieving the TCMSP and SwissADME databases to screen the active ingredients;using TCSMP database and SwissTargetPrediction database to predict the targets of active components;searching fracture targets in OMIM and GeneCards database;String database and Cytoscap software were used to construct protein-protein interaction network;GO function and KEGG pathway enrichment analysis were completed by using MetaScape database,and the component-target-pathway network map of pathways with large association with fracture healing was pictured;the core components and key targets were also screened through the network node degree values.Finally,the molecular docking mode of the core components of Taohong Siwu Decoction with key targets was verified by AutoDockTools software.RESULTS 49 components were identified in Taohong Siwu Decoction by mass spectrometry,mainly including phenylpropanoids,phenylpeptides,phenylethanosides,flavonoids,terpenes,coumarins,organic acids.Network pharmacology predicted AGE-RAGE,PI3K-Akt,EGFR,MAPK,and IL-17 are the main pathways,quercetin,gallic acid,caffeic acid,chlorogenic acid,ferulic acid,amygdalin,paeoniflorin,catalpol,etc.are the core components,and PTGS2,MAPK1,EGFR,BCL2,VEGFA,CASP3,IL6,MMP2,etc.are the key targets that Taohong Siwu Decoction promoting fracture healing.Molecular docking results showed that quercetin,paeoniflorin,and amygdalin could strongly bind together with PTGS2 and IL6 targets.CONCLUSION Taohong Siwu Decoction promotes fracture healing through the comprehensive action of multi-component,multi-target and multi-pathway.This study provides a scientific basis for its clinical application.
作者
杜克群
江华娟
李敏敏
成颜芬
马川
段毅
杨青波
傅超美
何瑶
DU Ke-qun;JIANG Hua-juan;LI Min-min;CHENG Yan-fen;MA Chuan;DUAN Yi;YANG Qing-bo;FU Chao-mei;HE Yao(Key Laboratory of Traditional Chinese Medicine Standardization of the Ministry of Education,College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Sichuan Chengdu 611137,China;Guizhou Yibai Pharmaceutical Co.,Ltd.,Guizhou Guiyang 550008,China)
出处
《中国医院药学杂志》
CAS
北大核心
2023年第6期633-643,668,共12页
Chinese Journal of Hospital Pharmacy
基金
四川省科技计划项目(编号:2021YFS0256)。
