机构地区:[1]中国人民解放军战略支援部队特色医学中心,北京100101 [2]中国人民解放军陆军军医大学第一附属医院,重庆400038
出 处:《中国药业》2022年第24期23-32,共10页China Pharmaceuticals
基 金:重庆市科卫联合中医药科研项目[2019ZY023488];中国人民解放军战略支援部队特色医学中心医药卫生科研课题[19ZX72]。
摘 要:目的 探讨化肝煎对慢性胃炎和非酒精性脂肪性肝病(NAFLD)异病同治的网络药理学作用机制。方法 利用中药系统网络药理学数据库和分析平台(TCMSP)收集化肝煎中的可能药物活性成分,并预测其作用靶点。通过GeneCards,OMIM,TTD数据库获得疾病相关靶点,借助Venny 2.1在线软件获得化肝煎治疗慢性胃炎和NAFLD的交集靶点。采用Cytoscape_v 3.8.0软件绘制药物-活性成分-靶点网络图,String数据库和Cytoscape_v 3.8.0软件绘制交集靶点蛋白相互作用(PPI)网络图,R语言软件进行基因本体论(GO)生物功能富集分析及京都基因与基因组百科全书(KEGG)通路富集分析。将节点度值排名前3的靶蛋白与其对应药物活性成分进行分子对接验证。结果 筛选得化肝煎中槲皮素、山柰酚、柚皮素、川陈皮素等23个活性成分;获得药物治疗慢性胃炎和NAFLD潜在靶点36个,其中关键靶点有白细胞介素1β、表皮生长因子受体、细胞肿瘤抗原P53、肿瘤坏死因子(TNF)、白细胞介素6(IL-6)等。预测其可能作用于晚期糖基化产物-晚期糖基化终末产物受体(AGE-RAGE)信号通路、Janus酪氨酸蛋白激酶-信号转导及转录激活因子(JAK-STAT)信号通路、白细胞介素17(IL-17)等信号通路发挥作用。分子对接结果显示,化肝煎主要活性成分角鲨烯、槲皮素、芍药苷、山柰酚、4-氧-甲基-芍药苷能与靶蛋白白蛋白(ALB)、IL-6、TNF-α很好地结合。结论 化肝煎通过多成分、多靶点、多通路的协同作用,影响炎症进展、脂质累积、氧化应激而发挥疗效。Objective To investigate the network pharmacology of the mechanism of Huagan Decoction in the treatment of chronic gastritis and non-alcoholic fatty liver disease(NAFLD) based on the theory of homotherapy for heteropathy.Methods The potential active components of Huagan Decoction and the corresponding targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The disease-related targets were obtained by the GeneCards,OMIM and TTD databases,and the common targets of Huagan Decoction in the treatment of chronic gastritis and NAFLD were obtained by the Venny 2. 1 online software. The drugs-active components-targets network was drawn by the Cytoscape_v 3. 8. 0 software. The protein-protein interaction(PPI) network of common targets was drawn by the String database and Cytoscape_v 3. 8. 0 software.The GO biological function enrichment analysis and the KEGG pathway enrichment analysis were performed by the R software.The top three target proteins with the higher degrees and their corresponding active components of drugs were verified by the molecular docking.Results Twenty-three active components of Huagan Decoction were screened out,including quercetin,kaempferol,naringenin and nobiletin. Thirty-six potential targets of Huagan Decoction in the treatment of chronic gastritis and NAFLD were obtained,some of which were key targets,including interleukin-1 β(IL-1 β),epidermal growth factor receptor(EGFR),cellular tumor antigen P53(TP53),tumor necrosis factor(TNF),interleukin-6(IL-6) and so on. The above key targets might play a role through the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE) signal pathway,Janus tyrosine protein kinase-signal transduction and activator of transcription(JAK-STAT) signal pathway,interleukin-17(IL-17) signal pathway and so on. The results of the molecular docking showed that the main active components of Huagan Decoction(squalene,quercetin,paeoniflorin,kaempferol and 4-O-methyl-paeoniflorin) c
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