Shahrekord University of Medical Sciences Journal of Herbmed Pharmacology 2345-5004 15 1 2026 01 01 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 51 65 10.34172/jhp.2026.53202 EN Payal Chauhan https://orcid.org/0000-0002-7417-6768 Karan Wadhwa https://orcid.org/0000-0002-0524-1714 Himanshu Sachdeva https://orcid.org/0009-0003-9341-0200 Govind Singh https://orcid.org/0000-0001-7906-5744 Journal Article 10.34172/jhp.2026.53202 2025 06 12 2025 08 17 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 (AlCl3)-induced neuronal damage in Drosophila. Methods: Following dose optimization via 7-day toxicity and 14-day survival assays, flies (50 per vial) were exposed to AlCl3 and various treatments for 7 consecutive days. On 7th 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<0.001). 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 AlCl3 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.