Exploration of potential mechanism of Rehmanniae Radix Praeparata in treatment of type 2 diabetes mellitus based on bioinformatics and experiment
Objective To investigate the biological mechanisms of Shudihuang(Rehmanniae Radix Praeparata)in treating type 2 diabetes mellitus(T2DM)through bioinformatics,network pharmacology,and experimental validation.Methods T2DM mice were treated with an aqueous extract of Rehmanniae Radix Praeparata by gavage,and the components that entered the blood and pancreas were identified using ultra-performance liquid chromatography-high-resolution mass spectrometry(UPLC-HRMS).Potential targets were predicted in the Swiss Target Prediction database and compared with genes from the Gene Expression Omnibus(GEO)datasets GSE15932 and GSE25724,the Comparative Toxicogenomics Database(CTD),and the GeneCards database to identify common genes.The complex network analysis and visualization with Cytoscape software were performed intersection analysis of targets in the blood and pancreas.Toxicity prediction,molecular docking,and mRNA-miRNA-lncRNA interaction network analysis were conducted in the ADMETab3.0 database.The main biological functions were analyzed using the GeneMANIA database,supported by validation through real-time fluorescent quantitative PCR experiments.Results Rehmanniae Radix Praeparata significantly improved abnormal glucose levels and enhanced glucose tolerance in mice with T2DM.A total of 138 compounds were identified in the blood,with 18 corresponding potential gene targets and one cluster,while 359 compounds were identified in the pancreas,with 141 potential gene targets and six clusters.Transthyretin(TTR)and ATP binding cassette subfamily B member 1(ABCB1)were identified as common gene targets in the blood and pancreas.The mRNA-miRNA-lncRNA interaction network containing six identical miRNAs and fourteen identical lncRNAs were constructed.The main biological functions involved lipid transport and metabolism,drug transport,ion and neurotransmitter transport,vascular processes,and inflammation regulation.Rehmanniae Radix Praeparata affected the mRNA expression levels of TTR and ABCB1 in the blood and pancreas of T2DM mice.Conclusion TTR and ABCB1 can be considered as potential therapeutic targets for Rehmanniae Radix Praeparata in the treatment of T2DM,providing a basis for T2DM treatment and offering insights for further research into the role of Rehmanniae Radix Praeparata in T2DM-related issues.
bioinformaticsnetwork pharmacologytype 2 diabetes mellitusRehmanniae Radix PraeparatatransthyretinATP binding cassette subfamily B member 1
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