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.

Insulin resistance causes decreased uptake of glucose which promotes susceptibility of type 2 associated neurological impairments.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.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).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.