Zerumbone augments cognitive enhancement potentials of EPA+DHA: Insight from a hyperlipidemic rat model.

Hyperlipidemia and cognitive dysfunction (CD) are the two public health concerns. Though
hyperlipidemia has been comprehensively studied in respect of cardiovascular diseases, its
role on CD needs to be explored. Hence, we evaluated hyperlipidemia as a risk factor for CD,
and the efficacy of eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA,
22:6n-3), and zerumbone (Z) in modulating CD under hyperlipidemic conditions. Male
Wistar rats (Rattus norvegicus) were fed control, high-fat (HF), high-fat + fish oil (HF+F),
high-fat + zerumbone (HF+Z), and high-fat + fish oil + zerumbone (HF+F+Z) containing
diet. After 30 days feeding trial, memory parameters [(Morris water maze, elevated plus maze
(transfer latency), and T-maze (spontaneous alteration)], and locomotor skills (open field test
and rotarod test) were assessed. Hyperlipidemia significantly (p<0.05) reduced memory and
motor coordination skills compared to control. However, the administration of EPA+DHA
and zerumbone significantly (p<0.05) restored the hyperlipidemia-induced loss of memory
and motor coordination skills. Collectively, our data imply that hyperlipidemia causes CD by
decreasing the memory and motor coordination skills, and administration of EPA+DHA and
zerumbone prevent hyperlipidemia induced CD. The augmented effect of EPA+DHA,
together with zerumbone, discloses a promising strategy for lowering the severity of CD in
hyperlipidemic conditions.