Neuroprotective Effects of 6-Paradol on Okadaic Acid-Induced Cognitive Impairment in Zebrafish

Introduction

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Natural compounds with antioxidant and anti-inflammatory properties are increasingly explored as potential therapeutic agents. 6-Paradol, a bioactive component of ginger, has demonstrated neuroprotective activity in preclinical studies. This study investigated the effects of 6-paradol on cognitive deficits induced by okadaic acid (OKA) in zebrafish (Danio rerio).

Methods

Adult zebrafish were exposed to OKA (10 nM) for 4 days to induce memory impairment and divided into six experimental groups (n = 10/group): control, galantamine (1 mg/L, positive control), OKA alone, and OKA combined with 6-paradol at 1, 3, or 6 μg/L. 6-Paradol was administered over 7 days with intermittent water changes. Cognitive performance was assessed using the Y-maze test (spatial memory) and Novel Object Recognition (NOR) test (recognition memory).

Results

Exposure to OKA significantly impaired both spatial and recognition memory. Galantamine reversed these deficits, validating the model. Treatment with 6-paradol at 3 and 6 μg/L significantly improved cognitive performance, increased exploration of the novel arm in the Y-maze, enhanced preference for the novel object in NOR, and stimulated locomotor activity. The lowest dose (1 μg/L) showed no significant effect.

Conclusions

These results suggest that 6-paradol mitigates OKA-induced memory deficits in zebrafish, likely through neuroprotective and cholinergic modulatory mechanisms. The findings support further investigation of 6-paradol as a candidate for AD therapy.