Baru ( <i>Dipteryx alata</i> ) nut oil attenuates amyloid-β-induced cognitive deficits by modulating neuroinflammation and BDNF signaling pathway

<b>Introduction:</b> Current treatments for Alzheimer's disease (AD) are primarily supportive and have limited efficacy in slowing disease progression. Therefore, the search for new therapeutic agents is essential to improve cognitive deficits or potentially prevent the advancement of this neurodegenerative disorder. <i>Baru oil (BO)</i> contains several bioactive compounds that may possess neuroprotective effects. However, no studies have investigated the potential beneficial effects of BO in the context of AD.<b>Aim and Methods:</b> This study aimed to investigate the neuroprotective effects of BO in a rodent model of AD. Mice were pretreated orally with vehicle or BO 1 or 3 g/kg/day for 45 days. On the 30th day, mice were infused i.c.v with amyloid-beta (Aβ) or PBS. A positive control group was orally treated with memantine (20mg/kg/day) for 15 days after Aβ or PBS infusion. Following behavioral assessments, mice were euthanized and the brains were removed for biochemical assays.<b>Results:</b> Similar to memantine treatment, pretreatment with both doses of BO prevented Aβ-induced memory impairments in the Morris water maze and the object recognition task. Pretreatment with BO 3g/kg/day prevented Aβ-induced increase in lipid peroxidation in the hippocampus. BO pretreatment mitigated the Aβ-induced reductions in hippocampal expression levels of BDNF, TrkB, and p-CREB. BO prevented the Aβ-induced increase in COX-2 and NOS-2 expression in the hippocampus.<b>Conclusion:</b> BO reversed Aβ-induced cognitive deficits. These neuroprotective effects were associated with the mitigation of hippocampal oxidative stress and neuroinflammation, alongside the restoration of the BDNF/TrkB/p-CREB signaling pathway. Our findings highlight Baru oil as a promising multifactorial therapeutic agent for AD.