基于网络药理学和实验验证探讨木瓜抗胃衰老的作用机制  

Exploration of the Mechanism of Chaenomeles speciosa Against Gastric Aging Based on Network Pharmacology and Experimental Validation

作　　者：王晓 舒恒 李洁[1] 何毓敏[2] 贺海波[1,3] 袁成福 张继红[4] 李浩然[4] 邹坤[1] 汪鋆植[1] WANG Xiao;SHU Heng;LI Jie;HE Yu-min;HE Hai-bo;YUAN Cheng-fu;ZHANG Ji-hong;LI Hao-ran;ZOU Kun;WANG Jun-zhi(Hubei Key Laboratory of Natural Products Research and Development,Yichang Key Laboratory of Development and Utilization of Health Products with Drug and Food Homology,China Three Gorges University,Yichang 443002,China;Medical College of China Three Gorges University,Yichang 443002,China;Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Shiyan 442000,China;Chinese Medicine Clinical Medical College,Hubei Clinical Research Center for Functional Digestive Diseases of Traditional Chinese Medicine,China Three Gorges University,Yichang 443002,China)

机构地区：[1]三峡大学天然产物研究与利用湖北省重点实验室,药食同源大健康产品开发利用宜昌市重点实验室,湖北宜昌443002 [2]三峡大学医学院,湖北宜昌443002 [3]武当特色中药研究湖北省重点实验室,湖北十堰442000 [4]三峡大学中医临床医学院,湖北省功能性消化系统疾病中医临床医学研究中心,湖北宜昌443002

出　　处：《中国药学杂志》2023年第13期1166-1177,共12页Chinese Pharmaceutical Journal

基　　金：湖北省科技厅自然科学基金项目资助(2022CFB357,2022CFB427);湖北省宜昌市科学技术局自然科学基金项目资助(A21-2-044);武当特色中药研究湖北省重点实验室开放基金项目资助(WDCM2022010)。

摘　　要：目的网络药理学和分子对接、体外实验验证探究木瓜抗胃衰老的作用机制。方法使用中药系统药理学数据库与分析平台(TCMSP)、中药分子机制生物信息学分析工具数据库(BATMAN-TCM)、文献查阅和Swiss ADME平台获取木瓜活性成分及潜在靶点,利用GeneCard数据库收集衰老相关基因,借助String平台构建木瓜抗胃衰老蛋白互作网络(PPI),随后使用DAVID平台完成基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析,再通过分子对接验证、细胞实验探究木瓜抗胃衰老的作用机制。结果网络分析结果表明筛选得到木瓜抗胃衰老主要成分35个,重要靶点63个,其作用机制可能与癌症通路、磷脂酰肌醇-3-激酶/蛋白质激酶蛋白B(PI3K/AKT)信号通路等有关;体外实验显示,木瓜提取物明显降低D-半乳糖所致的人胃黏膜上皮细胞(GES-1)活性氧(ROS)、β-半乳糖苷酶水平,增加p-PI3K、p-AKT、磷酸化的糖原合成激酶-3β(p-GSK3β)、β-连环蛋白(β-catenin)表达和减轻G0/G1期周期阻滞。结论表明了木瓜抗胃衰老多成分、多靶点、多途径协同作用的特点,为抗胃衰老的药物开发和临床应用提供实验依据。OBJECTIVE To explore the underlying mechanism of Pseudocydonia sinensis against gastric aging by network pharmacology,molecular docking,and in vitro cell experiments.METHODS The composition and potential targets of Pseudocydonia sinensis were obtained by using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM),literature review and Swiss ADME;aging related genes were collected using GeneCard database,aging genes and potential targets of Pseudocydonia sinensis were imported into string platform to build protein-protein interaction(PPI)network,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were completed by using David platform,and then the anti-aging mechanism of Pseudocydonia sinensis was verified by molecular docking and cell experiments.RESULTS According to the prediction results,35 main components and 65 chief targets of Chaenomeles speciosa against gastric aging were obtained,the mechanism of action may be related to the cancer pathway,phosphatidylinositol 3-kiases/protein kinase B(PI3K/AKT)signaling pathway.In vitro experiments demonstrated that the extract of Pseudocydonia sinensis could significantly reduce the level of reative oxygen species(ROS)andβ-galactosidase,elevate the protein expressions of p-PI3K,p-AKT,p-GSK3β,β-catenin and alleviate G0/G1 cell cycle arrest in D-galactose induced human gastric epithelial cells(GES-1).CONCLUSION This study manifested the characteristics of multi-component,multi-target and multi-channelsynergistic action of Pseudocydonia sinensis against gastric aging,and also provided experimental basis for drug development and clinical application of anti-gastric senescence.

关 键 词：木瓜 胃衰老 网络药理学 分子对接 分子机制 

分 类 号：R966[医药卫生—药理学]