Pharmacological mechanism of Dendrobium nobile for type 2 diabetes mellitus by bioinformatics and in vitro experiment
OBJECTIVE To elucidate the pharmacological mechanism of Dendrobium nobile for type 2 diabetes mellitus(T2DM)by bioinformatics and in vitro experiment.METHODS Potential targets of D.nobile extract for treating T2DM were screened through bioinformatic databases for constructing protein-protein interaction(PPI)network.GO enrichment analysis of gene ontology and KEGG pathway enrichment analysis were performed with DAVID database for constructing a"Drug-Compound-Target-Pathway-Disease"network.Autodock Vina 1.1.2 was utilized for molecular docking of selected core targets and core compounds.MTT method was utilized for examining the protective effect of Dendrobium nobile on streptozotocin(STZ)-induced insulinoma β(INS-1)cell injury model and insulinoma β(NIT-1)cell injury model.The effect of D.nobile extract on core targets of insulin signaling pathway in NIT-1 cells was analyzed by Western blot and in vitro experiment.RESULTS The results of GO enrichment analysis showed that the treatment of T2DM by Dendrobium nobile was mainly corre-lated with the process of insulin regulation.The results of KEGG pathway enrichment analysis revealed that Dendrobium nobile treated T2DM through the signaling pathways of PI3K-AKT,FOXO and AGE-RAGE in diabetic complications,insulin resis-tance,lipid and atherosclerosis and insulin signaling pathway.Five core targets of AKT1,SRC,EGFR,MAPK1 and PIK3CA were selected.Six core compounds were gigantol,moniliformin,moscatilin,tristin,dihydroconiferyl and trans-N-coumaroyltyramine.Core targets had decent binding activities with core compounds and binding energy was＜-6.7 kcal·mol-1.Dendrobium nobile extract could improve the injury of INS-1/NIT-1 cells induced by STZ,protect islet β cells and play a role in treating T2DM.Dendrobium nobile extract could boost the protein expression levels of p-PI3K,p-PI3K/PI3K,p-AKT and p-AKT/AKT in injured pancreatic βcells(P＜0.01).CONCLUSION Dendrobium nobile extract protects the function of pancre-atic islet β cells and improves insulin synthesis and secretion through PI3K-AKT pathway in insulin signaling pathway,thereby treating T2DM.
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