苦瓜苷活性成分干预糖尿病潜在靶点及作用机制

Study on the potential target and mechanism of Momordica charantia glycoside active components in intervention of diabetes

苦瓜作为一种药食两用食品,其中苷类成分有利于控制糖尿病的发展,但其具体的分子作用机制尚不明确,因此,通过网络药理学和分子对接方法,探讨苦瓜苷降糖作用的潜在分子机制。首先,通过文献检索收集苦瓜苷活性成分,通过数据库筛选得到符合类药五原则的活性成分;预测活性成分的靶点,找到活性成分对应的基因;检索获取糖尿病疾病相关靶点;取交集得到共同靶点。其次,构建PPI(protein-protein interaction)网络,对网络中的节点进行筛选,得到苦瓜苷治疗糖尿病的核心靶点,对核心靶点进行GO(gene ontology)和KEGG(Kyoto encyclopedia of genes and genomes)功能分析;最后,将核心靶点与相关苦瓜苷活性成分进行分子对接验证。结果表明,筛选得到苦瓜苷治疗糖尿病的核心靶点主要为PPARG、STAT3、MAPK3等靶点,这些靶点主要参与了促进胰岛素刺激、胰岛素抵抗等生物学过程;分子对接显示,Momordicine I、Momordicoside I、Charantal等苦瓜苷活性成分与PPARG、STAT3、MAPK3等靶点存在较强的结合作用。这些结果说明苦瓜苷可能通过作用于PPARG、STAT3、MAPK3等靶点,参与调控胰岛素刺激、胰岛素抵抗等代谢过程,从而发挥治疗糖尿病的作用。研究结果初步阐明了苦瓜苷治疗糖尿病的分子机制,为进一步探究苦瓜苷治疗糖尿病提供了新的方向。

The glycosides in bitter gourd are beneficial to control the development of diabetes as the bitter gourd is used both as food and medicine,but their specific molecular mechanism of action is still unclear.The study was to explore the potential molecular mechanism of the hypoglycemic effect of mo‐mordica side by using network pharmacology and molecular docking methods.Firstly,the active ingre‐dients of momordica baldica were collected by literature search,and the active ingredients conforming to the five principles of drug class were screened by database.The target of the active ingredient was predicted and the corresponding gene of the active ingredient was found.Diabetic disease related tar‐gets were retrieved.The intersection was used to obtain in a common target.Then,protein-protein inter‐action(PPI)networks were built,the nodes in a network were screened so as to get the core target of balsam pear glycosides treatment of diabetes,the core target gene ontology(GO)and the Kyoto ency‐clopedia of gene and genome(KEGG)were analyzed.Finally,the core target of balsam pear was veri‐fied by molecular docking with related momordicin active ingredients.The results showed that the se‐lected core targets of momordicin in the treatment of diabetes were mainly PPARG,STAT3,MAPK3 and other targets,which were mainly involved in the promotion of insulin stimulation,insulin resistance and other biological processes.Molecular docking also showed that Momordicine I,Momordicoside I,Charantal and other momordicoside active ingredients had strong binding effect with PPARG,STAT3,MAPK3 and other targets.These results suggest that momordicin may play a role in the treatment of diabetes by acting on PPARG,STAT3,MAPK3 and other targets,and participating in the regulation and promotion of insulin stimulation,insulin resistance and other metabolic processes.This study prelimi‐narily shows the molecular mechanism of momordica in the treatment of diabetes mellitus and provides a new direction for further exploration of momordica in the treatment of diabetes mellitus.