Piperine-Coated Gold Nanoparticles Alleviate Paraquat-Induced Neurotoxicity in Drosophila melanogaster

Parkinson's disease (PD) is the most common progressive neurodegenerative disease known to impart bradykinesia leading to diverse metabolic complications. Currently, scarcity of effective drug candidates against this long-term devastating disorder poses a big therapeutic challenge. Here, we have synthesized biocompatible, polycrystalline, and uniform piperine-coated gold nanoparticles (AuNPspiperine) to specifically target paraquat-induced metabolic complications both in Drosophila melanogaster and SH-SY5Y cells. Our experimental evidence clearly revealed that AuNPspiperine can effectively reverse paraquat-induced lethal effects in both in vitro and in vivo model systems of PD. AuNPspiperine were found to suppress oxidative stress and mitochondrial dysfunction, leading to inhibition of apoptotic cell death in paraquat-treated flies. AuNPspiperine were also found to protect SH-SY5Y cells against paraquat-induced toxicity at the cellular level preferably by maintaining mitochondrial membrane potential. Both experimental and computational data point to the possible influence of AuNPspiperine in regulating the homeostasis of parkin and p53 which may turn out to be the key factors in reducing PD symptoms. The findings of this work may facilitate the development of piperine-based nanoformulations against PD.