Exploring the combined protective effect of Rosa damascena and Commiphora wightii in alleviating aluminum-induced neurotoxicity in Drosophila melanogaster: Insights from behavioural, synaptic, mitochondrial, and oxidative dysfunction

Introduction: Metals are crucial for cellular physiology; however, their excessive accumulation triggers neuronal damage and leads to the progression of diverse neurodegenerative disorders, notably Alzheimer’s disease (AD). Accumulating evidence explored several plants and their active metabolites with established antioxidant properties as critical therapeutic interventions to allay metal-mediated neurotoxicity. In this avenue, both Rosa damascena and Commiphora wightii have demonstrated significant antioxidant and neuroprotective behaviours. Thus, the present research investigated the effects of R. damascena, C wightii, and their significant phytoconstituents, per se and in combinations, in the aluminum chloride (AlCl۳)-induced neuronal damage in Drosophila. Methods: Following dose optimization via ۷-day toxicity and ۱۴-day survival assays, flies (۵۰ per vial) were exposed to AlCl۳ and various treatments for ۷ consecutive days. On ۷th day, the oxidative stress markers, the level of neurotransmitters and mitochondrial complexes were assessed following locomotion and memory assessment. Results: Results demonstrated that R. damascena and C. wightii per se enhanced motor activity and exhibited antioxidant potential in fruit flies, and their combination showed more significant improvement (P<۰.۰۰۱). Similarly, a noteworthy modulation in the mitochondrial complexes and neurotransmitter levels was also observed. Moreover, their phytoconstituents combination, i.e. geraniol and guggulsterone, respectively, was also found effective in mitigating the neurotoxic effect induced by AlCl۳ overexposure, demonstrating a significant improvement in neuroprotective effect in flies. Conclusion: The overall outcomes suggest the potential of R. damascena and C. wightii or their combination as therapeutic agents for aluminum-induced neuronal toxicity and related neurodegenerative conditions.