BIOACTIVE COMPOUND-RICH EXTRACT MITIGATES COGNITIVE DECLINE AND ENHANCES RECOGNITION MEMORY IN A HIGH-FAT DIET-INDUCED OBESITY MODEL

Obesity is a serious public health issue with a global increase in its incidence and prevalence. Its pathophysiology, characterized by a state of chronic low-grade inflammation and insulin resistance, extends its effects to the central nervous system, negatively impacting cognition. In turn, bioactive compounds from fruits and vegetables have shown the ability to mitigate the deleterious effects of obesity on cognitive health by reducing neuroinflammation, oxidative stress, and insulin resistance. In this context, the aim of this study was to evaluate the effect of a bioactive compound–rich extract on cognitive decline using the novel object recognition (NOR) test in animals with diet-induced obesity. The extract is under confidentiality due to potential patent protection. Sixty male Swiss mice, four weeks old, were acclimated for four weeks in a controlled environment (22 ± 2°C, 60–70% humidity, inverted 12h/12h light-dark cycle). After eight weeks, the animals were randomly divided into four groups (n = 15): (1) Control; (2) Control + extract; (3) Obese; and (4) Obese + extract. During the experiment, the diet was replaced every two days, and body weight was measured weekly. In the 12th week, cognitive function was assessed through the novel object recognition (NOR) test. At the end of the experiment, the animals were anesthetized with ketamine and xylazine for blood collection via cardiac puncture. For statistical analysis, a one-way ANOVA was performed, followed by Tukey’s multiple comparison test. A significance level of 5% (p ≤ 0.05) and analyses were conducted using the GraphPad Prism 9 software. In the NOR test, the control group treated with the extract showed a higher discrimination index than the untreated control group (p = 0.0034), indicating improved memory performance. Similarly, the obese group treated with the extract outperformed the untreated obese group (p = 0.0004), demonstrating a protective effect of the extract against obesity-induced alterations. Diet-induced obesity is known to cause recognition memory deficits mediated by neuroinflammation, gut microbiota imbalance, and brain insulin resistance. In this context, bioactive compounds such as rhein and teasaponin restore cognitive function by targeting these same pathways, reducing neuroinflammation, increasing hippocampal BDNF, and modulating gut microbiota, suggesting that reversing these pathophysiological mechanisms is key to the observed effect. In conclusion, the results showed that the extract not only reversed cognitive deficits in obese animals but also enhanced memory in healthy ones. These findings highlight the potential of the extract for the prevention and treatment of obesity-associated cognitive decline.