Corosolic Acid Attenuates Cognitive Deficits, Oxidative Stress, Neuroinflammation and Corticohippocampal Neurodegeneration in D-galactose-Induced Alzheimer’s Disease in Adult Wistar Rats

Abstract

Background: Alzheimer’s disease is characterised by progressive corticohippocampal dysfunction driven by oxidative stress, neuroinflammation and cholinergic decline. Corosolic acid, a pentacyclic triterpenoid, possesses antioxidant and anti-inflammatory activity, but its effect on the corticohippocampal axis in a chronic ageing model is unknown. This study evaluated the neuroprotective effect of corosolic acid, relative to donepezil, in D-galactose-induced neurotoxicity in adult male Wistar rats. Methodology: Rats were exposed to D-galactose (120 mg/kg/day, orally, 42 days) and treated with corosolic acid or the reference drug donepezil. Learning and memory were assessed by the Morris water maze, Y-maze spontaneous alternation and novel object recognition tests. Superoxide dismutase (SOD) activity, nuclear factor kappa B (NF-κB) and acetylcholinesterase (AChE) were quantified in the prefrontal cortex and hippocampus. Neuronal and neurofibrillary architecture was examined by haematoxylin and eosin (H&E) and Bielschowsky silver staining. Results: D-galactose significantly impaired performance across all three behavioural paradigms, reduced SOD activity, elevated NF-κB and AChE, and produced marked neuronal degeneration and neurofibrillary fragmentation in the prefrontal cortex and hippocampal CA3 (p < 0.05). Corosolic acid significantly reversed each of these changes, restoring escape latency, spontaneous alternation and novel-object exploration toward control values, normalising SOD, NF-κB and AChE in both regions, and preserving neuronal and neurofibrillary integrity. On several endpoints — notably novel object recognition and cortical SOD activity — corosolic acid matched or exceeded the protection afforded by donepezil. Conclusion: Corosolic acid confers multi-domain neuroprotection against D-galactose-induced corticohippocampal injury, acting on oxidative, inflammatory, cholinergic, and structural endpoints, with efficacy comparable to or superior to that of donepezil on several measures. These findings identify corosolic acid as a promising candidate for further investigation in age-related neurodegeneration.