Gold-Containing Compound Auranofin Ameliorates 6-OHDA Induced Neurotoxicity in Rats: Via Targeting PI3K/Akt/GSK-3β Signalling

Abstract

The prevalence of parkinsonism is increasing worldwide, not only in age groups but now becoming a favourite of adults. As the onset is increasing in developed and underdeveloped countries, the current therapy lacks a permanent cure. Therefore, the research has used the gold-containing compound auranofin (AUF) in its neuroprotective form. The research was conducted to decipher the neuroprotective potential of AUF hybrid nanoparticles (AUFHNPs) using the in silico and in vivo 6-OHDA models. The in silico study was performed using CDOCKER software and the binding affinity of AUF with PI3K (5DXT), AKT (1UNQ), GSK-3β (1Q41), Nrf2 (2DYH), and HO-1 (1N45) were assessed. Then, intra-striatal unilateral injection of 6-OHDA (10 μg/2 μL) was given to rats with the help of stereotaxic surgery. After performing the amphetamine challenge test, rodents were treated with AUF (10 mg/kg) and AUFHNPs (5 and 10 mg/kg) for 21 days. All the behaviour parameters were performed on the last 2 days, and animals were sacrificed; brains were isolated for oxidative stress, neuroinflammatory, apoptotic, histological, and molecular marker analysis. In the docking study, AUF offered the highest binding score of −61.1231 with GSK-3β. In vivo administration of AUF and AUFHNPs significantly restored motor and behaviour alterations observed in open field tests, narrow beam walks, and grip strength meter. It also restored morphological changes and increased expression of pPI3K/pAKT, followed by inhibition of GSK-3β. Thus, the AUFHNPs were more significant than AUF alone and exerted neuroprotection via modulation of PI3K/AKT/GSK-3β signalling pathways.