摘要
目的 基于超高效液相色谱-四极杆-飞行时间串联质谱(ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry, UPLC-Q-TOF-MS)技术结合网络药理学探讨大果木姜子水提物治疗胃溃疡的活性成分及机制。方法 称取大果木姜子100 g采用水煎法制备大果木姜子水提物;称取新绿原酸、隐绿原酸、木兰花碱及柚皮苷对照品适量制备对照品溶液,称取大果木姜子水提物粉末0.5 g制备供试品溶液,采用UPLC-Q-TOF-MS技术分析大果木姜子水提物的化学成分;运用网络药理学方法分析并筛选大果木姜子水提物治疗胃溃疡潜在活性成分、核心靶点及重要信号通路,最后采用分子对接技术进行验证。结果 从大果木姜子水提物中鉴定出化学成分26个,主要是有机酸、生物碱及糖苷类;“成分-交集靶点”及分子对接验证结果表明波尔定碱、木兰花碱、紫堇定碱、新绿原酸及羟基酪醇葡萄糖苷是大果木姜子水提物治疗胃溃疡的潜在活性成分;蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络分析表明表皮生长因子受体(epidermal growth factor receptor, EGFR)、信号转导及转录激活因子3(signal transducer and activator of transcription 3,STAT3)、非受体酪氨酸激酶(sarcoma virus protein, SRC)、AKT丝氨酸/苏氨酸激酶1(AKT serine/threonine kinase 1,AKT1)及热休克蛋白90α家族A类成员1(heat shock protein 90 alpha family class A member 1,HSP90AA1)为核心靶点;基因本体论(gene ontology, GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)分析显示大果木姜子水提物可能通过调节磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase, PI3K)-蛋白激酶B(protein kinase B,Akt)、丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)、鼠肉瘤病毒癌基因同源物(rat sarcoma virus oncogene homolog, Ras)等信号通路,抑制炎症反应、促进细胞增殖以及调节靶蛋白磷酸化,发挥治疗胃溃疡的作用。结论 本研究对大果木姜子水提物化学成分进行表征,其治疗胃溃疡的机制可能与EGFR、STAT3、SRC、AKT1、HSP90AA1等作用靶点及PI3K-Akt、MAPK、Ras等信号通路有关。
Objective To explore the active components and mechanisms of the aqueous extract of Cinnamomum migao in treating gastric ulcer based on ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technology combined with network pharmacology.Methods 100 g of Cinnamomum migao was used to prepare the aqueous extract by decoction.Appropriate amounts of Neochlorogenic acid,Cryptochlorogenic acid,Magnolofrine,and Naringenin were used to prepare the reference solution.0.5 g of the powdered aqueous extract of Cinnamomum migao was used to prepare the test solution.The chemical components of the aqueous extract of Cinnamomum migao were analyzed using UPLC-Q-TOF-MS technology.The potential active components,core targets and important signaling pathways of the aqueous extract of Cinnamomum migao in gastric ulcer treatment were analyzed and screened using network pharmacology technology,which were then verified using molecular docking technology.Results Twenty-six chemical components were identified from the aqueous extract of Cinnamomum migao,mainly including organic acids,alkaloids,and glycosides.The results of"component-intersection target"and molecular docking verified Boldine,Magnoflorine,(+)-Corydine,Neochlorogenic acid and Hydroxytyrosol glucoside were potential active components of the aqueous extract of Cinnamomum migao in treating gastric ulcer.Protein-protein interaction(PPI)network analysis revealed that epidermal growth factor receptor(EGFR),signal transducer and activator of transcription 3(STAT3),non-receptor tyrosine kinase SRC,AKT serine/threonine kinase 1(AKT1),and heat shock protein 90 alpha family class A member 1(HSP90AA1)were core targets.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analyses revealed that the aqueous extract of Cinnamomum migao may exert therapeutic effects on gastric ulcer by regulating signaling pathways such as phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt),mitogen-activated protein kinase(MAPK),and Ras oncogene homolog(Ras),thereby inhibiting inflammatory responses,promoting cell proliferation,and modulating target protein phosphorylation.Conclusion This study characterized the chemical components of the aqueous extract from Cinnamomum migao,suggesting its anti-ulcer mechanism involves EGFR/STAT3/SRC/AKT1/HSP90AA1 targets and PI3K-Akt/MAPK/Ras signaling pathways.
作者
朱星宇
付昌丽
周祖英
王沙沙
王爱民
迟明艳
黄勇
黄闻
郑林
ZHU Xingyu;FU Changli;ZHOU Zuying;WANG Shasha;WANG Aimin;CHI Mingyan;HUANG Yong;HUANG Wen;ZHENG Lin(State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine,Guizhou Medical University,Guiyang 550004,Guizhou,China;School of Pharmacy,Guizhou Medical University,Guiyang 550004,China;Engineering Research Center for Ethnic and Traditional Chinese Medicine Development and Application,Ministry of Education,Guizhou Medical University,Guiyang 550004,Guizhou,China;Department of Burn and Plastic Surgery,Affiliated Hospital of Guizhou Medical University,Guiyang 550001,Guizhou,China)
出处
《贵州医科大学学报》
2025年第7期1004-1016,共13页
Journal of Guizhou Medical University
基金
国家自然科学基金(U1812403)
贵州省科技计划项目(黔科合基础-ZK[2025]重点057,黔科合平台人才-GCC[2023]036,黔科合平台人才-CXTD[2023]019)
贵州医科大学博士启动基金项目(校博合J字[2024]030)。
关键词
大果木姜子水提物
胃溃疡
网络药理学
分子对接
成分分析
Cinnamomum migao aqueous extract
gastric ulcer
network pharmacology
molecular docking
components analysis
