药食资源山楂果防治2型糖尿病成分与作用靶点分析研究

目的 探究山楂果降血糖作用靶点及潜在的分子机制。方法 利用中药综合数据库(traditional Chinese medicines integrated database, TCMID)及中医药百科全书数据库(the encyclopedia of traditional Chinese medicine, ETCM)并结合文献报道获得山楂果活性成分, 通过Swiss Target Prediction数据库预测其作用靶点。使用GeneCards及在线孟德尔人类遗传数据库(online mendelian inheritance in man, OMIM)获取2型糖尿病(type 2 diabetes mellitus, T2DM)相关靶点, 与山楂果预测靶点取交集即为山楂果防治T2DM的治疗靶点。将交集靶点导入STRING数据库及Cytoscape 3.7.2进行蛋白质相互作用(protein protein interaction, PPI)、药物-靶点-疾病网络可视化, 并通过DAVID数据库平台进行基因本体(gene ontology, GO)功能分析及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes, KEGG)通路富集分析。结果 山楂果有效活性成分为12种, 其中槲皮素、熊果酸等作用较为重要, 对应157个靶基因与T2DM相关。PPI及文献检索结果显示磷脂酰肌醇-3激酶调节亚基1 (phosphatidylinositol 3-kinase regulatory subunit alpha, PIK3R1)、RAC-α丝氨酸/苏氨酸蛋白激酶1 (RAC-alpha serine/threonine-protein kinase, AKT1)、丝裂原活化蛋白激酶3、8、14 (mitogen-activated protein kinase 3、8、14, MAPK3、MAPK8、MAPK14)等可能是山楂果防治T2DM的重要作用靶点。KEGG通路富集分析主要涉及磷脂酰肌醇-3激酶/蛋白激酶B (PI3K/Akt)信号通路、叉头状转录因子O亚家族蛋白(FoxO)信号通路、催乳素(prolactin)信号通路等。结论 山楂果能多成分、多靶点、多途径的防治T2DM, 对其引起的胰岛素水平失调、炎症反应、免疫功能及糖脂代谢紊乱发挥关键的调节作用。

Study on the ingredients and targets of hawthorn fruit as medicine and food for prevention and treatment of type 2 diabetes

Objective To explore the hypoglycemic target and potential molecular mechanism of hawthorn fruit. Methods The active ingredients of hawthorn fruit were obtained from traditional Chinese medicines integrated database (TCMID), The Encyclopedia of Traditional Chinese Medicine (ETCM) datebase and literature reports, at the same time, the targets were predicted through the Swiss Target Prediction database. The targets of type 2 diabetes mellitus (T2DM) were retrieved from the Gene Cards and online mendelian inheritance in man (OMIM) databases, then the therapeutic targets for combating type 2 diabetes mellitus (T2DM) of Hawthorn fruit were obtained by the intersection. The intersection targets were imported into the STRING database and Cytoscape 3.7.2 to visualize protein protein`interaction (PPI) network and drug-target-disease network. And through the DAVID database to takethe gene ontology (GO) function and kyoto encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the targets. Results Twelve active ingredients of Hawthorn fruit were found, among which quercetin, ursolic acid were more important, corresponding to 157 targets linked to T2DM. PPI and literature showed that phosphatidylinositol 3 kinase regulatory subunit alpha (PIK3R1), RAC-alpha serine/threonine-protein kinase (AKT1), mitogen-activated protein kinase 3, 8, 14 (MAPK3, MAPK8, MAPK14), etc., may be the important targets of Hawthorn fruit to control T2DM. KEGG pathway enrichment analysis mainly involved PI3K-Akt signaling pathway, FoxO signaling pathway, prolactin signaling pathway and so on. Conclusion Hawthorn fruit can prevent and cure T2DM with multiple components, multiple targets and multiple pathways, and play a key role in regulating insulin level disorder, inflammatory response, immune function and glucose and lipid metabolism disorder caused by hawthorn fruit.