Proanthocyanidin from grape seed against rotenone-induced toxicity in Drosophila melanogaster: Insights from behavioural and antioxidant studies

Abstract

Exposure to rotenone, an environmental neurotoxin, is linked to neurodegenerative conditions through mechanisms involving oxidative stress and inflammation. This study investigated the neuroprotective effects of Proanthocyanidin from grape seed extract in Drosophila melanogaster subjected to rotenone toxicity. A focused assessment of the effects of a 1 mg/g PGS diet on D. melanogaster intoxicated with 500 μM rotenone over seven days was done. A combination of behavioral and biochemical assays was employed to evaluate antioxidant activities in vivo. Additionally, molecular docking of PGS against acetylcholinesterase a key enzyme in nervous system was investigated. The results indicated that the 1 mg/g of PGS diet significantly enhanced the lifespan of D. melanogaster. Furthermore, this concentration effectively mitigated oxidative stress, as evidenced by improvements in catalase, superoxide dismutase, glutathione S-transferase, and acetylcholinesterase activities, and restored nitric oxide levels, reinforcing its role in neuroprotective pathways. PSG bound to the same binding domain in acetylcholinesterase as rotenone but with higher proximity to HIS-362. However, PGS exhibited limited efficacy in reversing lipid peroxidation and showed minimal improvement in glutathione levels. Behavioral assessments revealed that the decline in locomotor activity due to rotenone exposure was significantly alleviated by the 1 mg/g Proanthocyanidin from grape seed extract diet. In conclusion, Proanthocyanidin from grape seed demonstrates significant neuroprotective potential against rotenone-induced toxicity in D. melanogaster through its antioxidant and anti-inflammatory actions, suggesting mitigating neurodegenerative effects.