Effects of <i>Eisenia bicyclis</i> Extract on Sleep Promotion in a Caffeine-Induced Insomnia Models

This study investigated the sleep-promoting effects of the brown alga <i>Eisenia bicyclis</i> (EB), which contains phlorotannins, using caffeine-induced insomnia models of <i>Drosophila melanogaster</i> and ICR mice. In flies exposed to caffeine, EB treatment dose-dependently normalized disrupted nighttime activity and total sleep duration, while high-dose EB significantly reduced sleep fragmentation by decreasing the number of sleep bouts. Locomotor tracking analysis further showed that EB attenuated caffeine-induced hyperactivity, reducing distance moved, velocity, and mobility to levels comparable with the normal and benzodiazepine (BDZ)-treated groups. In the pentobarbital-induced sleep test with mice, EB restored the caffeine-induced reduction in sleep duration, although sleep latency remained unaffected. Moreover, EB significantly reduced elevated brain malondialdehyde levels induced by caffeine, accompanied by increased expression of antioxidant-related enzymes. Neurochemical analyses revealed that EB enhanced the levels of γ-aminobutyric acid (GABA) and serotonin, as well as the expression of their receptors, effectively reversing caffeine-induced reductions. These findings suggest that EB exerts sleep-promoting effects by modulating behavioral activity, enhancing antioxidant defense, and regulating GABAergic and serotonergic neurotransmission. Collectively, our results support the potential application of EB as a marine algae-derived functional material with relevance for both the food and pharmaceutical industries in the management of sleep disorders.