河南中医2024，Vol.44Issue(7)：1070-1078,9.DOI:10.16367/j.issn.1003-5028.2024.07.0198
基于UPLC-Q-TOF-MS/MS技术和网络药理学探讨柔肝方抗肝纤维化的作用机制
Study on the Anti-Fibrotic Mechanism of Liver-Softening Formula Based on UPLC-Q-TOF-MS/MS Technology and Network Pharmacology
摘要
Abstract
Objective:To study the therapeutic mechanism of Liver-Softening Formula in treating liver fibrosis based on ultra-high-per-formance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS)technology and network pharma-cology.Methods:A total of 80 C57BL/J mice were randomly divided into the blank serum group and the group of drug-containing serum from Liver-Softening Formula,with 4 mice in each group.The data of blank serum and drug-containing serum from Liver-Softening For-mula were analyzed by UPLC-Q-TOF-MS/MS technology combined with Xcalibur software,and the blood-entering components of Liver-Softening Formula were identified combined with secondary mass spectrum.By using Swiss Target Prediction database and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the targets of blood-entering components in Liver-Softening Formula were searched.The targets of liver fibrosis were searched using GeneCards,OMIM,PharmGKB,DrugBank Online,and Therapeutic Target Database databases.Using Cytoscape software,a"disease-compound-target"network was constructed,and the key components of Liver-Softening Formula in its anti-liver fibrosis effect were screened.The protein-protein interaction(PPI)network was constructed with the help of STRING database,and the core targets of Liver-Softening Formula in its anti-liver fibrosis were screened by topological analysis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)were analyzed using the DAVID database.Results:The main components of Ruogan prescription into blood included Oxysophocarpine,Sophocarpine,Scutellarein,Neobavaisoflavone,etc.A total of 303 related targets and 6 331 related targets of liver fibrosis,and 250 intersection targets of the two were obtained.The key components of Liver-Softening Formula in its anti-liver fibrosis effect include Quercetin,Apigenin,Kaempferol,Formononetin and so on.The core targets of Liver-Softening Formula in its anti-liver fibrosis effect included proto-oncogene tyrosine pro-tein kinase Src(SRC),signal transducer and activator of transcription 3(STAT3),mitogen activated protein kinase 1(MAPK1),ser-ine/threonine protein kinase B(PKB,also known as AKT1),etc.The GO analysis mainly involved the Cytokine-mediated signaling pathway and the negative regulation of apoptotic process process,inflammatory response,protein kinase activity,etc.KEGG analysis mainly involved PI3K-Akt signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway,etc.Conclu-sion:Liver-Softening Formula may regulate PI3K-Akt,MAPK,IL-17 and other signaling pathways through quercetin,apigenin,kaemphiol and other compounds,and act on SRC,STAT3,MAPK1 and other targets,thus playing an anti-fibrosis role,reflecting the pharmacologi-cal characteristics of multi-components,multi-pathways and multi-targets.关键词
柔肝方/肝纤维化/UPLC-Q-TOF-MS/MS/网络药理学/入血成分/小鼠Key words
Liver-Softening Formula/liver fibrosis/UPLC-Q-TOF-MS/MS/network pharmacology/blood-entering components/mice分类
医药卫生引用本文复制引用
游丽萍,林佳成,李文轩,孔晓妮,高月求,王灵台,孙学华..基于UPLC-Q-TOF-MS/MS技术和网络药理学探讨柔肝方抗肝纤维化的作用机制[J].河南中医,2024,44(7):1070-1078,9.基金项目
国家自然科学基金项目(82074336,82374251) （82074336,82374251）
2023年上海市卫生健康领军人才计划项目(2022LJ013) （2022LJ013）
浦东新区卫生健康委员会学科建设项目(中医肝病临床专科重点学科)(PWZxq2022-04) （中医肝病临床专科重点学科）
2022年国家中医药管理局高水平中医药重点学科建设项目(中医肝胆病学)(zyyzdxk-2023060) （中医肝胆病学）
