Promnesic, anxiolytic, and antioxidant effects of mansorin A and mansonone G in the okadaic acid-induced zebrafish model of Alzheimer’s disease

Dementia, a complex, incurable clinical syndrome marked by progressive cognitive decline, encompasses various types, with Alzheimer's disease (AD) being the most prevalent. The annual increase in AD cases underscores the urgency for innovative antidementia treatments. Mansorin A (MA) and mansonone G (MG) exhibit antioxidant effects on the central nervous system. Given the close association between oxidative stress and AD pathology, MA and MG might alleviate AD-like symptoms. To investigate the anti-dementia potential of MA and MG, the promnesic, anxiolytic, and antioxidant potential of MA and MG were studied in an animal model of AD. A zebrafish model of AD was induced using okadaic acid 10 nm, resulting in cognitive decline, anxiety-like behavior, and elevated oxidative stress. MA and MG were then administered chronically through immersion at concentrations of 1, 3, and 6 μg/L. Behavioral tests, including Novel Object Recognition and Y-maze tests, were conducted to assess promnesic effects, while Novel Tank and Novel Object Approach tests were used to evaluate anxiolytic effects. Biochemical analysis was performed to gauge oxidative stress and cholinergic status in the animals' brains. Results demonstrate that MA and MG improved short-term recognition and spatial memory as well as anxiety-like states in the zebrafish model. Furthermore, MA and MG significantly reduced oxidative stress induced by okadaic acid by enhancing the activity of superoxide dismutase, glutathione peroxidase, catalase, and reduced glutathione. Malondialdehyde levels and acetylcholinesterase activity in the brain decreased. Overall, the promnesic, anxiolytic, and antioxidant effects highlight MA and MG as promising therapeutic solutions in managing dementia.