As one of the principal etiological determinants of irreversible progressive dementia, the pathogenesis of Alzheimer's disease (AD) is predominantly ascribed to the intracellular accumulation of neurofibrillary aggregates composed of hyperphosphorylated tau proteins within limbic and cortical regions, alongside the extracellular deposition of dense/diffuse β-amyloid neuritic plaques. AD represents a multifactorial, conformational, neurodegenerative disorder with a predominant proteinopathic character, exhibiting an insidious onset and an irreversible progression.
The selected experimental model, the 5xFAD mouse, exhibits severe amyloidosis, harboring five pathogenic mutations within the human transgenes APP (amyloid precursor protein) and PSEN1 (presenilin-1), leading to a fulminant disease progression. The experimental cohorts comprised a negative control, a positive control treated with galantamine (3mg/kg), and two groups per tested extract, corresponding to the two predefined concentrations (50mg/kg and 100mg/kg). The impact on cognitive performance was assessed through a battery of behavioral tests: Y-maze test (YMT), open-field test (OFT), novel object recognition test (NORT), elevated plus maze test (EPM), forced swimming test (FST), and radial arm maze test (RAM). The pharmacokinetic profiles of the investigated compounds were analyzed in silico using computational tools such as SwissADME and pKCSM.
The study highlights the neuroprotective potential of Rubus fruticosus extracts, demonstrating a significant enhancement in cognitive performance and exploratory activity across behavioral tests, alongside a marked reduction in stress levels, indicative of anxiolytic and antidepressant properties. In silico analyses revealed favorable pharmacokinetic attributes conducive to ameliorating memory deficits, including the capacity of the compounds to cross the blood–brain barrier, promising interactions with key molecular targets, and a bioactivity profile suggestive of drug-like potential.
The findings suggest that Rubus fruticosus extracts exhibit promising pharmacokinetic profiles and neuroprotective pharmacological potential, underscoring the imperative for further multifaceted, multidisciplinary investigations to validate their underlying mechanisms and clinical applicability.
