基于网络药理学及动物实验探究白及非多糖成分治疗胃溃疡的作用及机制  

Therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in treatment of gastric ulcer based on network pharmacology and animal experiment

作　　者：方敬贤 张炼 李晶 张涵瑞 刘丹 聂晶 叶晓川 FANG Jing-xian;ZHANG Lian;LI Jing;ZHANG Han-rui;LIU Dan;NIE Jing;YE Xiao-chuan(Hubei Key Laboratory of Resource Science and Chemistry in Chinese Medicine,Pharmacy Faculty,Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Center for ADR Monitoring,Wuhan 430071,China)

机构地区：[1]湖北中医药大学药学院中药资源与中药化学湖北省重点实验室,湖北武汉430065 [2]湖北省药品(医疗器械)不良反应监测中心,湖北武汉430071

出　　处：《中国中药杂志》2023年第16期4446-4458,共13页China Journal of Chinese Materia Medica

基　　金：湖北省科技重大专项(2020ACA007-05)。

摘　　要：使用网络药理学和动物实验的方法研究白及非多糖成分对胃溃疡的治疗作用及机制。首先采用UPLC-Q-TOF-MS/MS对白及非多糖部位的化学成分进行分析,并利用网络药理学的方法获取白及与胃溃疡的交集靶点,构建“药物-成分-靶点-疾病”网络。随后使用STRING数据库构建蛋白相互作用(PPI)网络,并采用Metascape数据库进行Gene Ontology(GO)及Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析,预测白及治疗胃溃疡的作用机制。最后构建酒精性胃溃疡小鼠模型,验证白及非多糖成分对胃溃疡的治疗作用及机制。从白及非多糖部位鉴定出47个化学成分,其中gymnosideⅠ(手参苷Ⅰ)、gymnosideⅡ(手参苷Ⅱ)、militarine(白及苷)、bletilloside A、shancigusinⅠ(山慈菇素Ⅰ)等可能为治疗胃溃疡的主要活性成分;PPI网络分析得到白蛋白(ALB)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤坏死因子(TNF)、表皮生长因子受体(EGFR)等核心靶点,KEGG通路富集分析显示白及非多糖成分主要通过调节PI3K-AKT信号通路、MAPK信号通路、Ras信号通路等多种通路发挥作用。动物实验结果显示,白及非多糖成分可显著改善酒精所致小鼠胃组织的溃疡状况,提高溃疡抑制率;能够显著降低血清肿瘤坏死因子-α(TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6、血管活性肠肽(VIP)和血栓素B2(TXB2)水平,显著升高IL-10、前列腺素E2(PGE2)、表皮生长因子(EGF)和血管内皮生长因子(VEGF)水平;同时能够显著降低胃组织中磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B(AKT)蛋白水平,显著升高p-PI3K、p-AKT蛋白水平。该研究表明白及在胃溃疡的治疗方面凸显出多成分、多靶点、多途径协同作用的特点,验证了网络药理学的部分预测结果,为临床应用提供了科学依据。The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments.UPLC-Q-TOF-MS/MS was employed to characterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma,and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology.The"drug-component-target-disease"network was constructed.Protein-protein interaction(PPI)network was established by STRING.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma.Finally,the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer.Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma,among which gymnosideⅠ,gymnosideⅡ,militarine,bletilloside A,and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer.PPI network analysis revealed core targets such as albumin(ALB),serine/threonine kinase 1(AKT1),tumor necrosis factor(TNF),and epidermal growth factor receptor(EGFR).The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,and Ras signaling pathway.The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate,decrease the levels of TNF-α,interleukin(IL)-1β,IL-6,vasoactive intestinal peptide(VIP),and thromboxane B2(TXB2),elevated the levels of IL-10,prostaglandin E2(

关 键 词：白及 非多糖成分 网络药理学 胃溃疡 PI3K/AKT 

分 类 号：R285[医药卫生—中药学]