Dual inhibition of DPP-4 and cholinesterase enzymes by phytoconstituents of an ethanolic extract of Prosopis cineraria pods: Therapeutic implications for the treatment of diabetes-associated neurological impairments.

BACKGROUND: Insulin resistance causes decreased uptake of glucose which promotes susceptibility of type 2 associated neurological impairments. METHODS: The study was aimed to evaluate inhibition potential of an ethanolic extract of Prosopis cineraria (EPC) pods against DPP-4 and cholinesterase enzymes by in-vitro, in-vivo and in-silico assessments. The present study consists of in vivo studies on diabetes induced rat model by HOMA (Homeostasis of model Assessment) and related parameters, in vitro studies through DPP-4 enzyme assay, cholinesterase assays using Ellman's reaction. The in-silico studies were conducted by molecular docking of Cinerin C with targeted enzymes. The phytochemical characterization of the extract was demonstrated through LCMS studies. The antioxidant studies of extract were performed by FRAP and TEAC assays. RESULTS: The extract showed 64.8% maximum inhibition of DPP-4, 34.91% inhibition of AChE and 74.35% inhibition of BuChE. Antioxidant capacity by an extract showed 847.81±16.25µM Fe2+ equivalent in case of FRAP assay and 0.40 ± 0.08 mmol/l of Trolox equivalent in TEAC assay. In vivo study shown competent glycaemic control against significant HOMA IR (1.5), HOMA % β (26.5) and HOMA % S (68.8) as well as pancreatic cell mass proliferation. The in-silico analysis also revealed positive pharmacophores interactions of Cinerin C with targeted enzymes (DPP4 and cholinesterase). CONCLUSION: It can be concluded that phytoconstituents of Prosopis cineraria pod extract may be significantly consider in neuropharmacology to resolve insulin resistance induced neurological complications as shown inhibition against DPP-4, AChE and BuChE targets enzymes.