Mechanism of Melastoma dodecandrum flavonoids in treatment of type 2 diabetes mellitus on network pharmacology and validation
Objective To study the mechanism of anti type 2 diabetes by Melastoma dodecandrum flavonoid by using the method of network pharmacology,and to verify the related targets by animal experiments.Methods To collect the chemical constituents of M.dodecandrum flavonoids through literature search,and screen the target of M.dodecandrum in treatment of type 2 diabetes based on the Swiss Target Prediction,GeneCards,TTD,and DrugBank databases platform.To construct the"active ingredients-type 2 diabetes-potential target"by Cytoscape 3.7.1 software.The target protein interaction network was constructed through the String platform,GO enrichment analysis and KEGG metabolic pathway were analyzed through the R language analysis platform.To construct type 2 diabetes mellitus model rats high-fat diet induction and ip administered with streptozotocin method.40 rats successfully modeled type 2 diabetes mellitus model were randomly divided into model group,metformin group(0.2 g/kg)group,and M.dodecandrum flavonoids(0.34,0.45,0.60 g/kg)groups,with 8 rats in each group.High-fat diet was continued and a control group was set up.Each group was given the corresponding drug intragaically once daily,the control group and model group were given 0.5% CMC-Na solution intragaically for 5 weeks.The body mass,water intake,and food intake of rats were recorded,and the related indexes of blood glucose and blood lipid of rats were detected.qPCR was used to detect the regulatory effects of M.dodecandrum flavonoids flavones on the targets of PI3K,Akt,and AMPK in liver tissue of type 2 diabetic rats.The protein expressions levels of Akt,AMPK,and SREBP-1c in liver tissues of rats in each group were detected by Western blotting.Results 8 Active ingredients such as quercetin,apigenin,naringin were screened from M.dodecandrum flavonoids and acted on 98 type 2 diabetes targets.GO function and KEGG enrichment analysis showed that M.dodecandrum flavonoids play an anti-diabetic role in type 2 diabetes mainly by regulating PI3K/Akt signaling pathway and AMPK related signaling pathway.Animal experiments confirmed that M.dodecandrum flavonoids can decrease FBG,inhibit the increase of blood lipid,up-regulate the mRNA expression of PI3K,Akt,and AMPK in liver of type 2 diabetic rats,and significantly increase the protein expression levels of Akt and AMPK,reduce the expression of SREBP-1C protein(P<0.01,0.05),can improve the metabolic disorders of sugar and lipid,and has a good anti-type 2 diabetes effect.Conclusion This study verified the characteristics of M.dodecandrum flavonoids in treatment of type 2 diabetes with multi-component,multi-target and multi-pathway.The anti-diabetic mechanism of of M.dodecandrum flavonoids may be related to the regulation of the expression levels of PI3K,Akt,AMPK,and SREBP-1C targets,thereby improving the disorder of glucose and lipid metabolism,providing a reference for further research on the mechanism of action.
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NSTL
万方数据
维普
