ANTI-DEMENTIA EFFECTS OF MANSORIN A, MANSONONE G, AND 6-PARADOL IN THE OKADAIC ACID-INDUCED ZEBRAFISH MODEL OF ALZHEIMER’S DISEASE

Introduction. Dementia is a clinical syndrome mainly characterized by progressive cognitive decline. Alzheimer's Disease (AD), the most prevalent type of dementia, is a priority in research as stated by the World Health Organization, given the annual surge of AD cases and its high economic impact. With unknown causes, dementia remains incurable. Mansorin A (MA), mansonone G (MG), and 6-paradol (PD) are plant-derived compounds with potential in AD treatment.

Methods. MA, MG, and PD were administered chronically via immersion in concentrations of 1, 3, and 6 μg/L to the novel okadaic acid-induced zebrafish model of AD obtained by immersion of animals in 10 nM okadaic acid. A battery of behavioral tests was conducted to assess the effect of administered substances on short-term recognition and spatial memory (Novel Object Recognition and Ymaze tasks, respectively) and anxiety (Novel Tank Diving and Novel Object Approach tests) in the animal model. Following, biochemical analysis was conducted to assess the oxidative stress and acetylcholinesterase levels in the brain. In silico analysis of absorption, distribution, metabolism, and excretion (ADME) parameters was also performed.

Results. The obtained results indicate promnesic, anxiolytic, and acetylcholinesterase inhibitory properties of MA, MG, and PD, as well as antioxidant effects by increasing the activity of catalase, superoxide dismutase, reduced glutathione, and glutathione peroxidase while reducing the levels of carbonylated proteins and malondialdehyde. Analysis of ADME parameters indicates that MA, MG, and PD are blood-brain barrier permeant and are drug-like molecules.

Conclusions. The results pose MA, MG, and PD as promising anti-AD agents.