Synergistic interplay between triazine and curcumin or resveratrol in mitigating rotenone-induced toxicity in Drosophila model

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, oxidative stress, and debilitating motor dysfunction. Targeting the Wnt signaling pathway provides a powerful disease-modifying strategy. Building on recent evidence that triazine derivatives modulate Wnt signaling, we used a Drosophila model and in silico molecular docking to validate the specific interactions driving this pathway modulation, followed by qPCR of key Wnt signaling-related genes: armadillo , wingless , and frizzled 3 . The neuroprotective efficacy of the triazine derivative, alone or in combination with curcumin or resveratrol, was subsequently evaluated using behavioral, neurochemical, biochemical, apoptotic, immunohistochemical, and ultrastructural assessments. Treatment with the triazine derivative produced marked neuroprotective effects, which were further enhanced when combined with curcumin or resveratrol. This treatment significantly restored dopamine levels and locomotor performance, enhanced superoxide dismutase and catalase activities, and reduced lipid peroxidation compared with untreated rotenone-exposed flies. Moreover, immunohistochemical analysis indicated attenuation of apoptotic signaling, while transmission electron microscopy revealed substantial preservation of neural ultrastructure. Collectively, these findings demonstrate the neuroprotective potential of the triazine derivative and suggest that its combination with curcumin and resveratrol may provide an enhanced strategy for counteracting oxidative stress, neural apoptosis, and motor dysfunction associated with PD. The findings further support Wnt signaling modulation as a promising mechanistic target and provide a rationale for further investigations of triazine-based combination strategies as potential disease-modifying approaches for PD.