Abrus precatorius leaf bioactives: invivo anti-diabetes mellitus type-1 activity, PPARA and SCD as novel targets

Abstract

AbstractAbrus precatorius (AP) is a medicinal plant rarely studied for its beneficial effects against diabetes mellitus (DM) type-1. We estimated DM type-1 related parameters—total protein (TP), direct bilirubin (DB), urea, creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and serum glucose (SG) after treatment with methanol extracts of AP leaves (APMLE) for 21 days, followed by histopathological analysis of kidney and liver sections. AP leaf bioactives (ALPBs) were collected from GCMS fractions, database, and literature; common targets were intersected with annotated DM type-1 genes from the experimental GSE14503 microarray dataset and genecard database. Overlapping differentially expressed genes were collected, and their protein–protein interaction network was analyzed using various bioinformatics tools: Enrichr, SRplot, GSEA, and Cytoscape, to provide insight into the potential molecular basis of APLBs in DM-type-1. 15 compounds were identified from GCMS analysis of APMLE. Antidiabetic potential of APMLE was observed with significant (p < 0.05) normalization of SG, TP, DB, ALT, AST, ALP, urea and creatinine while hepatorenal photomicrographs indicated moderate safety. Erucic acid, oleic acid, phytol and stigmasterol interacted with 25 type-1 DM biomarkers enriched in lipid and prostaglandin metabolic processes, neuroactive ligand receptor interaction, PPAR signaling pathway, diabetic cardiomyopathy, and cAMP signaling pathway. Furthermore, PPARalpha (peroxisome proliferator-activated alpha) and SCD (stearoyl-coenzyme A desaturase) were revealed as core biotargets interacting with APLBs via hydrogen bond, hydrophobic interaction, and van der Waals forces from the docking study. Future interests may provide additional experimental data into the mechanisms by which APLBs elicit this remarkable ability.