文献类型：期刊文献

中文题名：基于网络药理学与动物实验探究肉苁蓉总苷对炎症性肠病的作用机制

英文题名：The Mechanism of Total Glycosides of Cistanche deserticola Y.Ma on Inflammatory Bowel Disease Based on Network Pharmacology and Animal Experiments

作者：闫文杰[1];冯朵[1,2];张绍时[1];周士琦[1]

第一作者：闫文杰

机构：[1]北京联合大学生物化学工程学院生物活性物质与功能食品北京市重点实验室,北京100023;[2]农业农村部食物与营养发展研究所,北京100081

第一机构：北京联合大学应用文理学院|北京联合大学生物化学工程学院

年份：2023

卷号：23

期号：10

起止页码：1-11

中文期刊名：中国食品学报

外文期刊名：Journal of Chinese Institute Of Food Science and Technology

收录：CSTPCD;;Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：北京市属高校分类发展项目。

语种：中文

中文关键词：肉苁蓉总苷;网络药理学;炎症;炎症性肠病

外文关键词：total glycosides of Cistanche deserticola Y.Ma;network pharmacology;inflammation;inflammatory bowel disease

摘要：目的:通过网络药理学及动物实验研究,探讨肉苁蓉总苷对炎症性肠病(IBD)的潜在作用机制。方法:应用Pubchem数据库及文献收集肉苁蓉总苷中7种主要活性成分的三维结构。通过PharmMapper,UniProt,GeneCards等数据库获取活性成分相关靶点与IBD相关的基因靶点信息。再将肉苁蓉活性成分靶点和IBD的靶点绘制韦恩图,得到交集靶点,并将交集靶点上传到String数据库进行蛋白质-蛋白质相互作用(PPI)筛选分析。使用DAVID数据库将肉苁蓉总苷活性成分对IBD发挥保护作用的靶点进行基因本体(GO)功能富集、京都基因和基因组百科全书(KEGG)通路富集分析,采用Cytoscape 3.8.0软件构建“活性成分-靶点-通路网络”,预测肉苁蓉总苷治疗IBD的作用靶点与途径,并构建IBD小鼠模型进一步验证。结果:肉苁蓉总苷活性成分对IBD具有防护作用的靶点有254个,PPI分析筛选出核心靶点30个。GO功能富集和KEGG通路富集发现肉苁蓉总苷可能主要通过调控癌症通路、mTOR通路、TGF-β通路、JAK-STAT通路、AMPK通路等,进而影响细胞信号传导、增殖、分化、凋亡来发挥作用。动物实验结果表明,肉苁蓉总苷能有效缓解IBD小鼠体质量减轻及粪便出血,降低疾病活动指数,同时有效抑制脾脏中mTOR、TGF-β两个靶点蛋白的表达。通过对小鼠粪便的16S rDNA扩增子测序进行PICRUSt2基因功能注释,分析发现肉苁蓉总苷调控IBD疾病与小鼠体内细胞壁/细胞膜/包膜生物生成,脂代谢、糖代谢过程及相关防御信号转导机制有着密切关系,与网络药理学结果相符。结论:肉苁蓉总苷可以通过多成分、多靶点、多途径协同有效防止IBD,这为阐明肉苁蓉治疗IBD的临床应用提供了新方法和新思路。其具体机制及物质基础还需更深入的试验研究加以验证。
Objective:To investigate the potential mechanism of total glycosides of Cistanche deserticola Y.Ma on inflammatory bowel disease(IBD)through network pharmacology and animal experiments.Methods:The three dimensional structures of 7 main active components in total glycosides were collected by Pubchem database and literature.PharmMapper,UniProt,GeneCards and other databases were used to obtain the information of active ingredient related targets and IBD related gene targets.Then,the targets of Cistanche's active ingredients and IBD were mapped by Wayne diagram to obtain the intersection targets,and the intersection targets were uploaded to the String database for protein-protein interaction(PPI)screening analysis.Cytoscape 3.8.0 software was used to construct the‘active component-target-pathway network’for gene ontology(GO)functional enrichment and KEGG pathway enrichment analysis on the targets of the protective effect of total glycosides on IBD.To predict the target and pathway of total glycosides in the treatment of IBD,and construct mice model of IBD for further verification.Results:There were 254 protective targets of total glycosides against IBD,and 30 core targets were selected by PPI analysis.GO functional enrichment and KEGG pathway enrichment showed that total glycosides may play a role by regulating cancer pathway,mTOR pathway,TGF-β pathway,JAK-STAT pathway,AMPK pathway,etc.Then it affected cell signal transduction,proliferation,differentiation,and apoptosis.The results of animal experiments showed that total glycosides could effectively relieve weight loss and fecal bleeding in IBD mice,reduce disease activity index,and effectively inhibit the expression of mTOR and TGF-βin spleen.By sequencing 16S rDNA amplicon of mouse feces and annotating PICRUSt2 gene function,it was found that total cistanche glycosides regulate IBD disease and cell wall/membrane/envelope biogenesis in mice.Lipid metabolism,glucose metabolism and related defense signal transduction mechanism were closely related,which was consistent with the results of network pharmacology.Conclusion:Total glycosides could effectively treat IBD through multi-component,multi-target and multi-pathway synergism,which provided a new method and new idea for elucidating the clinical application of Cistanche in the treatment of IBD.However,its specific mechanism and material basis need to be verified by further experimental studies.