文献类型：期刊文献

中文题名：基于网络药理学及分子对接探讨红芪多糖改善糖尿病胃轻瘫的作用机制

英文题名：Mechanism of hedysarum polybotrys polysaccharide in improving diabetic gastroparesis based on network pharmacology and molecular docking

作者：郭倩[1];李荣科[1];张磊[1];魏昭晖[1];万生芳[1,2];邵晶[3]

第一作者：郭倩

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]甘肃中医药大学敦煌医学与转化教育部重点实验室,甘肃兰州730000;[3]甘肃中医药大学药学院,甘肃兰州730000

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2025

卷号：41

期号：6

起止页码：1158

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金资助项目(No 82060914);甘肃中医药大学2022年度中医学一级学科“岐黄英才”导师专项基金(博导-6、硕导-12);敦煌医学与转化教育部重点实验室开放课题(No DHYX23-02)。

语种：中文

中文关键词：红芪多糖;网络药理学;分子对接;糖尿病胃轻瘫;作用机制;实验验证

外文关键词：hedysarum polybotrys polysaccharide;network pharmacology;molecular docking;diabetic gastroparesis;mechanism of action;experimental verification

摘要：目的将网络药理学和分子对接技术与动物实验相结合,探讨红芪多糖(hedysarum polybotrys polysaccharide,HPS)治疗糖尿病胃轻瘫(diabetic gastroparesis,DGP)的关键核心靶点及作用机制,并用动物实验加以验证HPS对DGP的影响。方法查阅HPS的化学成分,并用TCMSP数据库收集红芪的有效化学成分。利用Swisstarget数据库筛选HPS活性成分靶点,通过疾病数据库(TTD、GeneCards、Drugbank、DisGeNET)筛选出DGP相关靶点信息;运用STRING数据库构建PPI网络;运用Cytoscape 3.10.1软件进行网络拓扑结构分析,筛选出关键靶点,并构建化合物-靶点-通路网络图,利用Metascape数据库对关键靶点进行GO功能(生物功能、分子功能和细胞功能)和KEGG通路富集分析;利用Pymol 2.5和AutoDock软件进行分子对接。并造模成DGP大鼠模型,HPS干预8周后HE染色观察小肠组织病理形态学改变,Western blot检测AGEs、RAGE、NF-κB蛋白表达。结果共获得关键靶点302个,并对关键靶点进行基因GO功能分析及KEGG通路富集分析,预测出CUL3、YWHAZ、NTRK1等为关键靶点,AGE-RAGE signaling pathway in diabetic complications,viral carcinogenesis,hepatitis B,alcoholism信号通路等为关键通路。另外体内实验验证HPS能改善DGP大鼠小肠组织病理形态学,对小肠组织有明显的保护作用,且能降低AGEs、RAGE、NF-κB蛋白表达,以达到治疗DGP的目的。结论HPS具有多成分、多靶点、多途径的作用特点,可能影响AGE-RAGE信号通路对DGP发挥调控作用,为后续临床改善DGP提供新的思路。
Aim To investigate the key targets and mechanisms of diabetic gastroparesis(DGP)by integrating network pharmacology and molecular docking technology with animal experiments,and to specifically focus on exploring the effects of hedysarum polybotrys polysaccharide(HPS)on DGP through animal experimentation to validate its potential as a treatment for diabetic gastroparesis.Methods The chemical constituents of HPS were analyzed,and the active chemical components of Radix Astragali were identified using the TCMSP database.The Swisstarget database was utilized to screen for HPS active ingredient targets,while DGP-related targets were identified from disease databases such as TTD,GeneCards,Drugbank,and DisGeNET.The STRING database was used to construct the PPI network,and Cytoscape 3.10.1 software was employed for network topology analysis and selection of key targets.Subsequently,a compound-target-pathway network diagram was constructed.Key targets underwent GO function(biological function,molecular function,and cellular function)and KEGG pathway enrichment analysis using the Metascape database.Molecular docking was performed using Pymol 2.5 and AutoDock software.DGP rat model was established to observe the histopathological changes in small intestine after eight weeks of HPS intervention through HE staining.Additionally,Western blot was conducted to detect the expression of AGEs,RAGE,and NF-κB in eggs.The results revealed a total of 302 key targets.Results A total of 302 key targets which were further analyzed for gene GO function and KEGG pathway enrichment.CUL3,YWHAZ,and NTRK1 were predicted as the key targets with critical pathways including the AGE-RAGE signaling pathway in diabetic complications,viral carcinogenesis,hepatitis B,and alcoholism signaling pathway among others.Furthermore,in vivo experiments confirmed that HPS could improve small intestine histopathology in DGP rats,resulting in significant protective effects on this organ.It also reduced the expression of AGEs,RAGE,and NF-κB protein,hence achieving its purpose of treating DGP.Conclusion HPS has the characteristics of multi-component,multi-target and multi-pathway action,which may affect the regulatory role of AGE-RAGE signaling pathway on DGP,and provide new ideas for the subsequent clinical improvement of DGP.