Cerebroprotective Potential of Hesperidin Nanoparticles Against Bilateral Common Carotid Artery Occlusion Reperfusion Injury in Rats and In silico Approaches

Abstract

Cerebral ischemia-reperfusion (C I/R) accelerates neuronal injury through the overproduction of reactive oxygen species due to mitochondrial dysfunction. Hesperidin has cerebroprotective effects due to its antioxidant and anti-apoptotic nature against oxidative damage caused by C I/R. The blood-brain barrier also limits the hesperidin passage into the cerebral region due to its poor bioavailability. Current research included analysis of binding energy, hesperidin inhibitory constant on inflammatory cytokines (TNF α, IL 6) and apoptotic protein (caspase 3), hesperidin nanoparticles prepared, and investigation of their defense against C I/R rats. Binding energy and IC50 of hesperidin on pathological proteins using AutoDoc. 1.5.6 and PyRx in silico tools were compared with thalidomide. The fabrication method was engaged in the preparing of nano-hesperidin, characterized by SEM assessment. Bilateral common carotid artery occlusion technique has been used in experimental rats to cause C I/R. Nano-hesperidin cerebroprotective activity was assessed by differing infarction magnitude, oxidative stress parameters, TNF α and IL 6, and hippocampal histopathology with rats treated with unformulated hesperidin. Hesperidin found stronger binding strength and IC50 was relative to thalidomide on TNF α, IL 6, and caspase 3. Nano-hesperidin with a size of 100–500 nm was shown in a uniform nano-size and spherical form. Nano-hesperidin-treated rats showed significantly increased glutathione (p\u2009<\u20090.00***), catalase (p\u2009<\u20090.01**), and total protein (p\u2009<\u20090.001***), and decreased cerebral infarction size, TNF α (p\u2009<\u20090.01**), IL 6 (p\u2009<\u20090.01**), and malondialdehyde (p\u2009<\u20090.05*), compared with hesperidin-treated ischemic rats. Therefore, hesperidin nanoparticles may confer protection to the neurons against ischemic injury compared with hesperidin treatment.