Depressive Effects on the Central Nervous System and Underlying Mechanism of the Enzymatic Extract and Its Phlorotannin-Rich Fraction from Ecklonia cava Edible Brown Seaweed

Abstract

Marine plants have been reported to possess various pharmacological properties; however, there have been few reports on their neuropharmacological effects. Terrestrial plants have depressive effects on the central nervous system (CNS) because of their polyphenols which make them effective as anticonvulsants and sleep inducers. We investigated in this study the depressive effects of the polyphenol-rich brown seaweed, Ecklonia cava (EC), on CNS. An EC enzymatic extract (ECEE) showed significant anticonvulsive (>500 mg/kg) and sleep-inducing (>500 mg/kg) effects on the respective mice seizure induced by picrotoxin and on the mice sleep induced by pentobarbital. The phlorotannin-rich fraction (PTRF) from ECEE significantly potentiated the pentobarbital-induced sleep at >50 mg/kg. PTRF had binding activity to the gamma aminobutyric acid type A (GABA_A)-benzodiazepine (BZD) receptors. The sleep-inducing effects of diazepam (DZP, a well-known GABA_A-BZD agonist), ECEE, and PTRF were completely blocked by flumazenil, a well-known antagonist of GABA_A-BZD receptors. These results imply that ECEE produced depressive effects on CNS by positive allosteric modulation of its phlorotannins on GABA_A-BZD receptors like DZP. Our study proposes EC as a candidate for the effective treatment of neuropsychiatric disorders such as anxiety and insomnia.

• Ecklonia cava
• phlorotannin
• anticonvulsive effect
• sleep-inducing effect
• gamma aminobutyric acid type A (GABA_A)-benzodiazepine receptor