Ameliorative Potential of Natural Antioxidants Against Paraquat-Induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster: A Comparative Study

Background: Natural antioxidants show neuroprotective potential to protect against neurodegenerative disorders in experimental animals. There is a need to characterize newer promising neuroprotective natural molecules. Objective: In the present study, we have compared the neuroprotective activity of 4hydroxyisophthalic acid (DHA-I), a novel natural antioxidant from the roots of Decalepis hamiltonii, with the other natural neuroprotective antioxidants, ellagic acid, quercetin and nicotinamide, against paraquat (PQ) neurotoxicity in D. melanogaster. Results: Flies exposed to multiple (sub-lethal) dose of PQ showed movement disorder characteristic of Parkinson’s disease (PD). The four natural antioxidants showed ameliorative effects against PQ neurotoxicity in the sub-acute model as seen in survivability, locomotor activity as well as oxidative stress markers including reactive oxygen species (ROS), lipid peroxidation and the endogenous antioxidant defenses. Conclusion: Our study shows that the antioxidant compounds exhibit varying degrees of protection against PQ-induced oxidative stress and neurotoxicity with DHA-I, quercetin, and nicotinamide being the most effective and ellagic acid, the least potent in Drosophila. Our results show that mitochondrial Mn-SOD is a critical target for PQ neurotoxicity and the neuroprotection by the antioxidants involves the attenuation of mitochondrial ROS production and oxidative damage.