摘要
目的:采用超高效液相色谱-四极杆-飞行时间质谱法(UPLC-Q-TOF-MS)鉴定吴茱萸的透皮成分,并运用整合药理学方法揭示吴茱萸经皮治疗腹泻的分子机制。方法:综合对照品比对,UNIFI系统解析和质谱裂解规律研究等方法,实现对吴茱萸透皮成分的快速鉴定。在此基础上,借助中医药整合药理学研究平台v2.0(TCMIP v2.0),SymMap,DisGeNET及相关文献,获取吴茱萸透皮成分的潜在作用靶标和腹泻相关疾病靶标。对疾病和药物靶标集进行拓扑分析以获得核心靶标,利用基因本体(GO)和京都基因与基因组百科全书(KEGG)数据库获得核心靶标的富集功能和通路,构建"透皮成分-核心靶标-关键通路"网络图。结果:从吴茱萸70%乙醇提取稠膏的透皮接受液中鉴定出包括喹诺酮类生物碱、柠檬苦素类、吲哚类生物碱、有机酸类和甾醇在内的19个化学成分。对药物和疾病靶标集进行拓扑分析获得174个吴茱萸经皮治疗腹泻的核心靶标,通过KEGG富集获得炎症反应、细胞增殖、信号转导、细菌感染、营养物质调节和能量代谢等信号通路。结论:吴茱萸的透皮成分通过作用于Rac家族蛋白、磷脂酰肌醇3-激酶、细胞色素P450酶和醛酮还原酶来参与肠道炎症调节,维护肠道黏膜的完整性,并通过修复和调整机体代谢发挥止泻作用,初步阐明了吴茱萸经皮治疗腹泻的分子机制。
Objective: To identify the transdermal constituents of Euodiae Fructus and predict its molecular mechanism in treating diarrhea by transdermal drug delivery. Method: Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)and integrated pharmacology methods were used. The rapid identification of transdermal constituents of Euodiae Fructus was realized by the means of comparison of reference substances,analysis of UNIFI system and mass spectrometry. On this basis,Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP)v2.0,SymMap,DisGeNET databases and literature were used to collected potential targets of transdermal constituents of Euodiae Fructus and targets for diarrhea-related diseases. The disease targets and drug targets were topologically analyzed to obtain the core targets,which were used for the Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis. Finally,Cytoscape 3.6.0 was used to build up a network of transdermal constituents-core targets-key pathways. Result:A total of 19 chemical constituents were speculatively identified from Euodiae Fructus extract, including quinolone alkaloids, limonins, indole alkaloids,organic acids and sterols. A total of 174 core targets of Euodiae Fructus for treating diarrhea were obtained by a topology analysis,signaling pathways of inflammatory response,cell proliferation,nutrient regulation and energy metabolism,signal transduction,bacterial infection were obtained through the analysis of KEGG enrichment. Conclusion: In this study,the transdermal constituents of Euodiae Fructus are identified for the first time,they can participate in the regulation of intestinal inflammation,maintain the integrity of intestinal mucosa,repaire and adjust the metabolism of the body by acting on Rac protein family,phosphatidylinositol 3-kinase,cytochrome P450 enzymes and aldo-keto reductase,respectively. In general,the molecular mechanism of Euodiae Fructus in the treatment of diarrhea is preliminarily elucidated.
作者
周建新
沈硕
杜茂波
李玉洁
孙奕
何爱萍
姚瑶
王明硕
刘淑芝
尹永芹
ZHOU Jian-xin;SHEN Shuo;DU Mao-bo;LI Yu-jie;SUN Yi;HE Ai-ping;YAO Yao;WANG Ming-shuo;LIU Shu-zhi;YIN Yong-qin(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Artemisinin Research Center,China Academy of Chinese Medical Sciences,Beijing 100700,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第7期112-120,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家级非物质文化遗产代表性项目-中医传统制剂方法[IX-4(1)]。
