Auranofin-loaded chitosan-lipid hybrid nanoparticle protects against rotenone model of Parkinson's disease via modulation of GSK-3β/ Nrf2/HO-1 signaling

Auranofin (AUF) is a gold-based compound that has demonstrated a wide range of biological effects, such as anti-inflammatory and antibacterial effects. However, the neuronal use of AUF is restricted due to its low bioavailability. Thus, to improve blood brain barrier (BBB) penetration and investigate its antiparkinsonian impact, the researchers developed AUF-loaded hybrid nanoparticles (AUFHNPs). This research delves into the neuroprotective potential of AUFHNPs against rotenone-induced Parkinson's disease (PD). The MTT assay, Acridine orange/Ethidium bromide (AO/EB) staining, RT-PCR, and Western blot analysis were performed on SH-SY5Y lines. Also, AUFHNPs were prepared and characterized. For the in-vivo study, AUF, its NPs and rotenone were administered for 28 days, and behavioral parameters were performed on day 27 and 28. On the 29th day, animals were sacrificed, and brains were isolated for biochemical assessment, apoptotic and inflammatory markers evaluation, histopathology, and molecular examination. In-vitro results showed that AUF significantly restored cell viability and reduced apoptosis. Spherical-shaped NPs were observed under FE-SEM/TEM analysis. Administration of AUFHNPs in rats significantly restored motor activity and neuronal morphological changes by phosphorylating GSK-3β to increase the expression of Nrf2/HO-1. This study concludes that developing AUFHNPs increases AUF's bioavailability in the brain and exerts neuroprotection via modulating GSK-3β/Nrf2/HO-1 pathways.