Neuroprotective effect of α‐pinene self‐emulsifying nanoformulation against 6‐OHDA induced neurotoxicity on human SH‐SY5Y cells and its in vivo validation for anti‐Parkinson's effect

Abstract

Oxidative stress (OS) is involved in the multifaceted pathogenic paradigm of neurodegenerative diseases like Parkinson's disease (PD). Monoterpenes like α-pinene (ALP) is considered to be a therapeutically potent antioxidant agent able to attenuate and scavenge various reactive oxygen species and reactive nitrogen species. The present study aimed to evaluate the in vitro and in vivo neuroprotective effect of αpinene self-emulsifying nanoformulation (ALP-SENF) for PD. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was done to evaluate the neurotoxic dose of the ALP-SENF; however, the neuroprotective effect was assessed by 6-hydroxydopamine (6-OHDA) induced neurotoxicity model on SH-SY5Y taking NAC (N-acetyl-L-cysteine) as standard. The in vivo anti-Parkinson's activity of the ALP-SENF was compared with that of the plain ALP suspension by using reserpine antagonism and haloperidol-induced Parkinsonism model in rats. Various behavioral tests and biochemical antioxidant enzymes were estimated. The in vitro results revealed that treatment with ALP-SENF at a concentration of 100 and 200 µM was found to show significant neuronal SH-SY5Y cell viability against 50 µM 6-OHDA. ALP-SENF treated animals have seen significant neurobehavioral improvement. Furthermore, the levels of antioxidative enzymes in biochemical test reveals a marked enhancement in the expression of antioxidant enzymes that significantly attenuated the OS induced neurodegeneration. Due to the mechanisms of their antioxidant action, it was probably due to the scavenging of free radicals and the expression of antioxidant enzymes. It also improved neurobehavioral changes induced by reserpine and haloperidol.