Neuroprotective effects of pectolinarin against cognitive impairment in Aβ25-35-induced mouse model

Abstract

The accumulation of beta-amyloid (Aβ) in the brain is a major risk factor for Alzheimer’s disease (AD). 5,7-dihydroxy 4',6-dimethoxyflavone 7-rutinoside (pectolinarin), a flavonoid, is well-known for its antioxidative and neuroprotective effects. This study investigated whether pectolinarin could improve cognitive impairment induced by Aβ25-35 in mice. Cognitive impairment was induced by administering Aβ25-35 via intracerebroventricular injection into the brains of mice at a concentration of 5 nM/µL, followed by oral administration of pectolinarin at doses of 5, 10, and 25 mg/(kg · day) for 14 days. The Aβ25-35 fragment, the most neurotoxic portion of the Aβ peptide, rapidly aggregates in the brain and is widely used to establish mouse models that mimic Alzheimer’s disease–like pathology. Behavioral tests demonstrated that pectolinarin-treated groups had significantly enhanced spatial and short-term cognitive abilities in the novel object recognition and T-maze tests, as well as improved long-term cognitive ability in the Morris water maze test, evidenced by reduced time to locate the hidden platform as training progressed. Western blot analysis revealed that, in the pectolinarin-treated group, amyloidogenic pathway-related proteins (i.e. amyloid precursor protein (APP), β-site APP cleaving enzyme, presenilin-1, and presenilin-2) were suppressed, whereas non-amyloidogenic pathway-related proteins (protein kinase C-α and a disintegrin and metalloproteinase domaincontaining protein 10) were activated. These findings suggest that pectolinarin ameliorates Aβ25-35-induced cognitive impairment and may serve as a promising natural therapeutic candidate for the treatment and prevention of AD.