📖 ABSTRACT/OVERVIEW
Background: Alzheimer's disease (AD) is characterised by progressive neurodegeneration driven in part by chronic neuroinflammation and amyloid-beta pathology. Picralima nitida, a rainforest plant found across South South and South East Nigeria, contains alkaloids with reported neuroprotective and anti-inflammatory activities. The mechanistic basis of its potential in AD remains uninvestigated. This study explores the effects of P. nitida alkaloid fractions on neuroinflammatory pathways in a streptozotocin-induced intracerebroventricular (ICV-STZ) rat model of AD. Methods: Alkaloid fractions were isolated and characterised by LC-MS. ICV-STZ AD model rats received oral alkaloid fractions at 50, 100, and 200 mg/kg daily for eight weeks alongside donepezil controls. Cognitive function was assessed by Morris water maze and novel object recognition. Neuroinflammatory markers (TNF-alpha, IL-1beta, IL-6, NF-kB pathway proteins) and amyloid-beta expression were quantified by ELISA and Western blot. Hippocampal histopathology and immunohistochemistry were performed. Results: Alkaloid fractions significantly reduced TNF-alpha, IL-1beta, and NF-kB activation in hippocampal tissue dose-dependently (p less than 0.01). Amyloid-beta deposition was reduced at the highest dose. Cognitive indices improved significantly in treated groups. No significant hepatotoxicity was observed. Conclusion: P. nitida alkaloids attenuate AD-like neuroinflammation through NF-kB pathway modulation. This mechanistic insight positions P. nitida as a candidate for neuroprotective drug development relevant to dementia management in African populations. Keywords: Picralima nitida, neuroinflammation, Alzheimer's disease, NF-kB, alkaloids
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