Structure-based drug design of pre-clinical candidate nanopiperine: a direct target for CYP1A1 protein to mitigate hyperglycaemia and associated microbes

Abstract

ABSTRACT Diabetes is attributed to an increased vulnerability to bacterial infection linked to unregulated hyperglycaemia. The present study highlights the formulation of nanoparticles with phyto-compound piperine (PIP) encapsulated within non-toxic biodegradable polymer poly-lactide co-glycolide (PLGA) which showed a variety in surface functionality, biocompatibility, and the ability to tailor an optimized release rate from its polymeric enclosure. The observations revealed that nanopiperine (NPIP) pre-treatment in mice inhibited alteration in hepatic tissue architecture and hepato-biochemical parameters in diabetes and its associated bacterial infections. NPIP also decreased the propensity of lipids to undergo an oxidation process and stabilized the membrane lipids in vivo, thereby lowering oxidative stress and preventing enzymatic activation of CYP1A1. This result is corroborated with the in silico molecular docking study where PIP binding with CYP1A1 gave −11.32 Kcal/mol dock score value. The antibacterial activity of PIP was further demonstrated by the in silico PIP and Ef-Tu protein-binding efficacy revealing −6.48 Kcal/mol score value which was coupled with the results of in vitro studies where the zone of inhibition assay with NPIP against Staphylococcus aureus and Escherichia coli. Thus, NPIP could serve as a potential drug candidate in modulating targeted proteins to inhibit the progression of hyperglycaemia and its associated microbes.