Bhratee_2025_Metab.Brain.Dis_40_155

Cognitive impairment is characterized by memory loss and difficulty in focusing, remembering, adhering to directions, and solving problems; commonly seen in an elderly population. Apigenin (APG) (4', 5, 7-trihydroxyflavone) is a flavonoid with several positive health benefits, including chemoprevention, antioxidant and can suppress inflammatory responses by inhibiting TNF-alpha and IL-1beta levels. In this experimental study, we observed the possible neuroprotective effects of APG in the zebrafish model exposed to Lansoprazole (LPZ), a proton pump inhibitor known to induce cognitive impairment through hyperactivation of GSK-3beta pathway. This experiment involves 12 adult zebrafish per group, where one group received LPZ (100 mg) as a toxin for 7 days and APG (25, 50, and 100 mg/kg) as treatment, while DPZ (5 mg/kg) served as a standard comparison over the same period. Neurobehavioral tests such as T-Maze, Novel Tank Test (NTT), and Novel Object Recognition (NOR) were performed. Several biochemical assessments were also performed to evaluate the level of lipid peroxidation (LPO), glutathione (GSH), nitrite (NO), acetylcholinesterase activity (AChEs), catalase activity, neurotransmitters (GABA and glutamate), neuroinflammatory markers (IL-1beta, TNF-alpha, and IL-10), and histopathological analysis. The results showed that apigenin enhanced memory function, improved neurotransmitter balance, decreased oxidative stress markers, regulated the production of proinflammatory cytokines, and inhibited GSK-3beta activity. Additionally, the co-administration of a GSK-3beta inhibitor further promoted neuroprotection and cognitive enhancement facilitated by apigenin, highlighting the importance of the GSK-3beta signaling pathway. These findings highlight the potential of apigenin as a natural compound for mitigating cognitive dysfunction. However, this study should also include long-term toxicity assessments and deeper molecular analysis to elucidate Apigenin's mechanism of action fully. Future research should address these gaps to validate its therapeutic potential.