Neuro-protective effects of nano-formulated hesperetin in a traumatic brain injury model of<i>Danio rerio</i>

Abstract

Understanding the mechanism behind neuronal regeneration is critical for treating ischemic stroke and traumatic brain injury. The presence of neural stem cells in and around the sub-ventricular zone of human and also in zebrafish is evidenced. In this current study, the neuro-protective potential of nano-formulated hesperetin on injury-induced neurogenesis in zebrafish was assessed. Nanoformulation of hesperetin was prepared by anti-solvent precipitation technique using sodium dodecyl sulfate (SDS) as the stabilizing agent. The synthesized particles were characterized using SEM, DLS, XRD and FT-IR. Anti-oxidant capacity of nano hesperetin (nHST) in <i>in vitro</i> followed by <i>in vivo</i> studies in a traumatic brain injury (TBI) model of adult zebrafish (<i>Danio rerio</i>), catalase activity, histological analysis and gene expression studies for the genes <i>Sox2, Nestin, Fabp7a</i> and <i>HuC</i> were carried out. The synthesized particles were found to be in nanoscale and SDS had successfully integrated with hesperetin. Moreover, nHST had a significantly higher anti-oxidant capacity <i>in vitro</i>. Catalase levels in nHST treated group were significantly restored compared to other groups. Histological studies supported reduced tissue damage on oral administration of nano-hesperetin as compared to other groups. Gene expression studies showed that nano-hesperetin at a concentration of 10 μM when administered orally induced proliferation of neural stem cells without inducing cell death.