Mansonone G as a Natural Neuroprotective Compound in a Zebrafish Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with a significant global impact, and current treatments provide limited benefits with frequent side effects. This has prompted growing interest in natural compounds with neuroprotective potential. Mansonone G, a natural compound isolated from Mansonia gagei, is recognized for its antioxidant and anti-inflammatory properties. The present study evaluated the effects of Mansonone G on memory using zebrafish (Danio rerio) as a preclinical AD model. Cognitive deficits were induced by exposing zebrafish to okadaic acid (OKA, 10 nM) for 4 days. Animals (n = 10 per group) were allocated to six groups: control (DMSO), galantamine (1 mg/L) as a positive control, OKA with DMSO (amnesia model), and OKA with Mansonone G at doses of 1, 3, or 6 μg/L. Mansonone G was administered every three days for 7 days with water renewal. Cognitive performance was assessed by the Y-maze test for spatial memory and locomotor activity and the Novel Object Recognition (NOR) test for recognition memory. OKA exposure significantly impaired memory and recognition (p < 0.0001), while galantamine restored cognitive performance. Treatment with Mansonone G at 3 and 6 μg/L significantly improved spatial memory and object recognition, with p < 0.001 for 3 μg/L and p < 0.00001 for 6 μg/L, and enhanced locomotor activity. The 1 μg/L dose had minimal impact. Mansonone G demonstrated neuroprotective effects by increasing exploratory behavior, improving recognition memory, and restoring cholinergic function in OKA-treated zebrafish, supporting its development as a natural therapeutic candidate for AD.