基于网络药理学解析黄精-枸杞防治2型糖尿病分子机制

Network Pharmacology-based Investigation on Mechanisms underlying Huangjing(Polygonati Rhizoma)-Gouqi(Lycii Fructus)in Prevention and Management of Type 2 Diabetes

目的 采用网络药理学方法探究典型药食同源植物黄精-枸杞联合改善2型糖尿病分子机制,为后期黄精和枸杞子资源深加工利用奠定基础。方法 利用中药系统药理学数据库与分析平台(TCMSP),以药代动力学参数为筛选指标,获取黄精、枸杞的潜在有效成分及其作用的蛋白质靶点。通过检索GeneCards数据库、OMIM数据库、TTD数据库获取疾病相关靶点,与药物靶点交集获取2型糖尿病潜在作用靶点,构建蛋白相互作用网络,结合Metascape数据库对交集靶点进行基因本体GO富集分析和KEGG通路富集注释。结果 发现黄精-枸杞子复配组分共有57个活性成分,在2型糖尿病1290个相关靶点中存在交集靶点132个,核心靶点主要包括MAPK、AKT1、PTGS2、NCOA2和PIK3CA等,主要富集在PI3K-Akt-、Foxo-、MAPK-和胰岛素信号等糖脂代谢通路等。结论 黄精-枸杞主要以槲皮素、豆甾醇、甲基原薯蓣皂苷、β-谷甾醇、黄芩素及黄豆素黄酮为核心活性成分,通过多通路、多靶点防治2型糖尿病。研究结果为开发靶向2型糖尿病等慢性代谢性疾病的黄精-枸杞功能性食品提供理论参考。

Objective To explore the mechanism of Huangjing(Polygonati Rhizoma)-Gouqi(Lyci Fructus)preventing and treating type 2 diabetes by using network pharmacology.Methods The potential effective components and protein targets of Huangjing(Polygonati Rhizoma)-Gouqi(Lycii Fructus)were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and were identified according to parameters of absorption,distribution,metabolism and excretion.The type 2 diabetes related genes were obtained by searching GeneCards,OMIM and TTD database.The target genes of the pair and disease-related genes were identified,and the regulatory network and PPI network map of the pair were constructed.GO analysis and KECG enrichment analysis were computed by using Metascape.Results A total of 57 bioactive components in Huangjing(Polygonati Rhizoma)-Gouqi(Lyci Fructus)were identified,including quercetin,stigmasterol,methylprotodioscin_qt,beta-sitosterol,baicalein and glycitein.Among 1290 type 2 diabetes related gene targets,132 belonged to the common targets of bioactive components and the disease,e.g.MAPK1,AKT1,PTCS2,MAPK3,NCOA2,PIK3CA and MAPK14.Results from GO and KEGG enrichment analyses indicated that Huangjing(Polygonati Rhizoma)-Gouqi(Lyci Fructus)preventing and treating type 2 diabetes through multiple pathways,i.e.PI3K-Akt,Foxo,MAPK signaling.Conclusion Key components of Huangjing(Polygonati Rhizoma)-Gouqi(Lycii Fructus),including quercetin,stigmasterol,methylprotodioscin_qt,beta-sitos-terol,baicalein and glycitein,may affect multiple gene targets in a synergistic manner to prevent and treat type 2 diabetes.The results provide theoretical references for developing Huangjing(Polygonati Rhizoma)-Gouqi(Lyci Fructus)based functional foods that could prevent chronic metabolic diseases such as type 2 diabetes.