Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cholinergic dysfunction, oxidative stress, and hippocampal neuronal loss. Scopolamine, a muscarinic receptor antagonist, is widely used to induce reversible cognitive impairment in rodents that reproduces key biochemical and behavioural hallmarks of AD. Apigenin, a naturally occurring flavonoid, and omega-3 fatty acids have each been reported to possess antioxidant and neuroprotective properties, but their combined effect against scopolamine-induced neurotoxicity has not been well characterised.
Objective: To evaluate the neuroprotective effect of apigenin, alone and in combination with omega-3 fatty acid, on cholinergic function and oxidative stress in a scopolamine-induced model of cognitive impairment in rats.
Methods: Adult Wistar albino rats were divided into six groups (n = 3/group): normal control, scopolamine (1 mg/kg, i.p., days 9–17) toxic control, donepezil (10 mg/kg, p.o.) standard control, apigenin low dose (25 mg/kg), apigenin high dose (50 mg/kg), and a combined apigenin (25 mg/kg) plus omega-3 fatty acid (100 mg/kg) group, all treated orally for 17 days alongside scopolamine. Spatial learning and memory were assessed by the Morris water maze (escape latency), and locomotor activity by digital actophotometer, on days 0, 9, 14, and 17. On day 17, brain acetylcholinesterase (AChE) activity and the oxidative stress markers malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were estimated, and hippocampal sections were examined histopathologically (H&E staining).
Results: Scopolamine produced significant cognitive and locomotor impairment, elevated AChE activity and MDA levels, depleted GSH, SOD, and CAT, and caused marked hippocampal degeneration compared with the normal control group (p < 0.001). Apigenin treatment attenuated these changes in a dose-dependent manner, and the combined apigenin–omega-3 fatty acid group showed the greatest improvement across behavioural, biochemical, and histopathological parameters, approaching values recorded in the standard (donepezil) group.
Conclusion: Apigenin exerts a dose-dependent neuroprotective effect against scopolamine-induced cognitive dysfunction, and its combination with omega-3 fatty acid produces a more pronounced protective response, indicating a complementary antioxidant and cholinergic-restorative action that supports further investigation of this combination as a candidate neuroprotective strategy.
