Acipimox as a potential antioxidant and neuromodulator mitigates high fat diet induced cognitive dysfunction

A derivative of niacin i.e. Acipimox (Acx), exhibits antioxidant properties among in vitro and in vivo studies; however, its potential application for managing neurological deficits remains largely unexplored. This study explores the impacts of Acx on various physiological and neurological factors, including food consumption, body weight control, cognitive functions, oxidative stress neuroinflammation responses, expression of serotonin (5-HT) metabolism, and 5HT1A receptor within the midbrain and cerebral cortex. A total of 48 male albino rats (n = 8 per group) was randomly assigned to six experimental groups: (1) Vehicle (Vh) + Normal diet (NoD) (2) NoD + Acx (25 mg/kg (low dose) (3) NoD + Acx (50 mg/kg) (high dose), (4) Vh + High fat-rich diet (Hifrd), (5) Hifrd + Acx (25 mg/kg)(6) Hifrd + Acx (50 mg/kg). Rats were administered their respective treatment for 8 weeks (56 days). A behavioral evaluation such as Morris Water Maze (MWM) to assess spatial memory performance and the Y-maze test to measure spontaneous behavioral changes. Following decapitation, brain tissue from the midbrain and cerebral cortex was carefully dissected for further analysis. The findings revealed that Hifrd led to memory deficits, increased body weight, and heightened food consumption, effects that were mitigated via repeated administration of both doses of Acx. Additionally, Hifrd triggered oxidative stress-related neuroinflammation, altered 5-HT metabolism, and affected receptor expression of 5HT1A in both the midbrain and cerebral cortex following changes that were significantly modulated by Acx. Owing to its antioxidant, anti-inflammatory, and neuromodulatory effects, Acx mitigates Hifrd-induced memory impairments. Based on these findings, it suggests that Acx may have the potential to improve cognitive function and modulate neurological parameters in Hifrd-fed rats; however, further studies are required to determine its therapeutic relevance.