Adedayo_2026_Front.Behav.Neurosci_20_1803200

BACKGROUND: Cognitive dysfunction and cardiometabolic disturbances frequently coexist in neurological and metabolic disorders. Chronic systemic inflammation in cardiometabolic syndrome may promote neuroinflammation, damaging neurons and synapses and impairing memory pathways. Cola nitida is a medicinal plant widely recognized for its stimulant and therapeutic properties, yet its neuroprotective and cardiometabolic effects remain underexplored. Objective: This study investigated the effects of methanol extract of Cola nitida (CN) in a mouse model of memory and metabolic dysfunction induced by scopolamine and dexamethasone. METHODS: Male mice were randomly divided into six groups (n = 5): control (saline), scopolamine (3 mg/kg), scopolamine + dexamethasone (0.2 mg/kg), CN (50 mg/kg) + scopolamine, CN + scopolamine + dexamethasone, and donepezil (1 mg/kg) + scopolamine + dexamethasone. Treatments lasted 7 days, followed by behavioral testing (Morris Water Maze, Y-Maze). Biochemical analyses included acetylcholinesterase activity, oral glucose tolerance, lactate/LDH, oxidative stress markers, and lipid profiles. Hippocampal histology assessed neurodegeneration, while molecular docking evaluated CN phytochemicals against proteins linked to glucose metabolism, oxidative stress, and cholinergic signaling. RESULTS: Co-administration of dexamethasone and scopolamine impaired memory, elevated AChE activity, fasting glucose, and oxidative stress in the brain and heart. CN treatment improved memory and glucose tolerance, reduced oxidative stress and AChE activity, and preserved hippocampal neuronal integrity. Docking revealed strong affinities of CN flavonoids and procyanidins for Akt, GLP-1 receptor, Keap1, AChE, and TYK2, implicating them in glucose regulation, redox balance, and cholinergic neurotransmission. CONCLUSION: These findings highlight the neuroprotective and cardiometabolic benefits of Cola nitida and support its therapeutic potential for cognitive and metabolic disorders.