基于血清药物化学和网络药理学的广藿香干预病毒性肺炎药效物质基础和作用机制研究  

Pharmacodynamic Material Basis and Mechanism of Pogostemon cablin in the Intervention of Viral Pneumonia:A Study Based on Serum Pharmacochemistry and Network Pharmacology

作　　者：李楚 荆文光 赵小亮[3] 马双成[2] 魏锋[2] 张玉杰[1] LI Chu;JING Wen-guang;ZHAO Xiao-liang;MA Shuang-cheng;WEI Feng;ZHANG Yu-jie(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;National Institutes for Food and Drug Control,Beijing 100050,China;Experimental Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]中国食品药品检定研究院,北京100050 [3]中国中医科学院医学实验中心,北京100700

出　　处：《中国现代中药》2023年第2期304-313,共10页Modern Chinese Medicine

基　　金：国家重点研发计划项目(2019YFC1711505);中国食品药品检定研究院中药民族药检定所学科建设项目(1020050090116);中药材及饮片质量控制重点实验室项目(2022GSMPA-KL02)。

摘　　要：目的:基于血清药物化学与网络药理学探究广藿香干预病毒性肺炎的药效物质基础和作用机制。方法:利用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱法(UPLC-Q-Exactive Orbitrap MS)对广藿香水煎液、大鼠空白血清及含药血清样品中的成分进行分析,应用Compound Discoverer 3.1化合物预测软件,结合二级谱图及已有文献,鉴定广藿香的入血成分。利用SwissTargetPrediction数据库获取广藿香入血成分的作用靶点,将关键词“viral pneumonia”输入GeneCards、DisGeNET、OMIM数据库检索得到病毒性肺炎的靶点基因,利用Cytoscape3.9.1软件构建蛋白质-蛋白质相互作用(PPI)网络,筛选关键靶点。利用DAVID数据库对成分-疾病交集靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:从大鼠血清中鉴定出12个入血成分,包括7个原型成分和5个代谢产物,原型成分分别是木犀草素-7-葡萄糖醛酸苷、芹菜素-7-O-葡萄糖醛酸苷、圣草酚-7,3′-二甲醚、芫花素、广藿香酮、4′,7-二甲基柚皮素、邻苯二甲酸二丁酯;丝氨酸/苏氨酸蛋白激酶B1(Akt1)、肿瘤坏死因子(TNF)、表皮生长因子受体(EGFR)、半胱氨酸蛋白酶3(CASP3)为PPI中的核心靶点;富集分析显示,广藿香入血成分可能通过调控磷脂酰肌醇3-激酶/Akt(PI3K-Akt)信号通路、卡波西肉瘤相关疱疹病毒感染、人类免疫缺陷病毒1型感染、TNF信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、Janus激酶-信号转导与转录(JAK-STAT)信号通路、白细胞介素-17(IL-17)信号通路等发挥抗病毒、抗炎作用。结论:广藿香中入血成分可能通过抗病毒、抗炎、细胞增殖和凋亡等相关的蛋白及通路发挥干预病毒性肺炎的作用。Objective:To reveal the pharmacodynamic material basis and mechanism of Pogostemon cablin in the intervention of viral pneumonia based on serum pharmacochemistry and network pharmacology.Methods:The components in P.cablin decoction,rat blank serum and drug-containing serum were analyzed by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS),and the absorbed components of P.cablin in serum were identified by Compound Discoverer 3.1 in combination with MS/MS profiles and existing literature.The targets of the absorbed components of P.cablin were retrieved from SwissTargetPrediction,and the target genes of viral pneumonia were searched from GeneCards,DisGeNET and Online Mendelian Inheritance in Man(OMIM)by input of the keyword viral pneumonia.Cytoscape 3.9.1 was employed to construct the protein-protein interaction(PPI)network and the key targets were screened,followed by Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the intersection targets by Database for Annotation,Visualization and Integrated Discovery(DAVID).Results:Twelve compounds were identified from rat serum,including 7 prototype components(luteolin-7-glucuronide,apigenin-7-O-glucuronide,eriodictyol-7,3′-dimethyl ether,genkwanin,pogostone,4′,7-di-O-methylnaringenin,dibutyl phthalate)and 5 metabolites.Serine/threonine kinase 1(Akt1),tumor necrosis factor(TNF),epidermal growth factor receptor(EGFR)and Caspase-3(CASP3)were the hub genes in PPI network.Enrichment analysis revealed that the absorbed components of P.cablin exerted the antiviral and anti-inflammatory effects via regulating phosphoinositide 3-kinase(PI3K)-Akt,Kaposi sarcoma-associated herpesvirus infection,human immunodeficiency virus 1 infection,TNF,mitogen-activated protein kinase(MAPK),Janus kinase(JAK)-signal transducer and activator of transcription(STAT)and interleukin-17(IL-17)signaling pathways.Conclusion:The absorbed components of P.cab

关 键 词：广藿香 血清药物化学 网络药理学 病毒性肺炎 药效物质基础 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学]