Allicin attenuates age-related cognitive and neural decline in a rat model by modulating amyloid burden and regulating BDNF/NrF2 gene expression.

Abstract

Aging is associated with a progressive decline in physiological functions, particularly in the central nervous system, often driven by oxidative stress and amyloid protein accumulation. Despite increasing evidence of the health benefits of garlic-derived compounds (allicin), the role of allicin in improving the age-related cognitive decline and its related neuronal damage remains poorly understood. So, this study aimed to evaluate the neurotherapeutic effects of allicin against aging-induced neuronal dysfunction, focusing on its antioxidant and anti-inflammatory actions. Forty-eight male Wistar rats were divided into six groups: young control (YC), old control (OC), and allicin-treated groups (20 mg/kg and 40 mg/kg for both young and old rats), with treatment administered orally for eight weeks. Various assessments, including neurobehavioral tests, the brain cerebral biomarker analysis, neurotransmitter levels, BDNF and NrF2 mRNA expression, antioxidative status, histopathological evaluations, and molecular docking analyses, were conducted. Results indicated that aging led to cognitive decline, increased anxiety behaviors, oxidative stress, DNA damage, neuroinflammation, amyloid-beta (Aβ 1-42) accumulation, and reduced BDNF and NrF2 gene expression. Allicin treatment alleviated these issues by restoring neurotransmitter function, boosting antioxidant defenses, reducing inflammation and amyloid burden, and upregulating BDNF and NrF2 expressions. Histopathological and molecular docking results further supported these findings. Allicin exhibited potent neurotherapeutic impacts against age-related neural degeneration, highlighting its potential as a therapeutic agent to counteract brain aging. This study emphasizes the emerging role of food-based bioactive compounds like allicin in promoting brain health, mitigating the age-related neurodegenerative conditions and opening the door for future nutraceutical applications.