TY - JOUR
T1 - Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor
T2 - A novel neurological activity of seaweed polyphenols
AU - Cho, Suengmok
AU - Yang, Hyejin
AU - Jeon, You Jin
AU - Lee, C. Justin
AU - Jin, Young Ho
AU - Baek, Nam In
AU - Kim, Dongsoo
AU - Kang, Sung Myung
AU - Yoon, Minseok
AU - Yong, Heim
AU - Shimizu, Makoto
AU - Han, Daeseok
PY - 2012/6/1
Y1 - 2012/6/1
N2 - The primary objective was to investigate whether seaweeds have hypnotic activity. Methanol extracts of 30 seaweeds were screened for their binding activity at the GABA type A-benzodiazepine (GABA A-BZD) receptor, a well-characterised molecular target for sedative-hypnotics. The most active seaweed was Ecklonia cava Kjellman (ECK). An ethanol extract of ECK (ECK-E) significantly potentiated pentobarbital-induced sleep in mice. In four solvent fractions separated from ECK-E, hypnotic activity was proportional to contents of total phenols and total phlorotannins, known as seaweed polyphenols. Major phlorotannins of the ethyl acetate (EtOAc) fraction with the highest activity were eckol, eckstolonol, dieckol, and triphlorethol-A, and their K i (binding affinity, μM) values for [ 3H]-flumazenil binding were 1.070, 1.491, 3.072, and 4.419, respectively. Hypnotic effects of ECK-E and the EtOAc fraction were fully inhibited by flumazenil, a specific GABA A-BZD receptor antagonist. These results imply that phlorotannins of ECK induce sleep by positive allosteric modulation of the GABA A-BZD receptor.
AB - The primary objective was to investigate whether seaweeds have hypnotic activity. Methanol extracts of 30 seaweeds were screened for their binding activity at the GABA type A-benzodiazepine (GABA A-BZD) receptor, a well-characterised molecular target for sedative-hypnotics. The most active seaweed was Ecklonia cava Kjellman (ECK). An ethanol extract of ECK (ECK-E) significantly potentiated pentobarbital-induced sleep in mice. In four solvent fractions separated from ECK-E, hypnotic activity was proportional to contents of total phenols and total phlorotannins, known as seaweed polyphenols. Major phlorotannins of the ethyl acetate (EtOAc) fraction with the highest activity were eckol, eckstolonol, dieckol, and triphlorethol-A, and their K i (binding affinity, μM) values for [ 3H]-flumazenil binding were 1.070, 1.491, 3.072, and 4.419, respectively. Hypnotic effects of ECK-E and the EtOAc fraction were fully inhibited by flumazenil, a specific GABA A-BZD receptor antagonist. These results imply that phlorotannins of ECK induce sleep by positive allosteric modulation of the GABA A-BZD receptor.
KW - Ecklonia cava Kjellman
KW - Edible seaweeds
KW - GABA type A-benzodiazepine receptor
KW - Hypnotic activity
KW - Phlorotannin
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U2 - 10.1016/j.foodchem.2011.08.040
DO - 10.1016/j.foodchem.2011.08.040
M3 - Article
AN - SCOPUS:84862798191
VL - 132
SP - 1133
EP - 1142
JO - Food Chemistry
JF - Food Chemistry
SN - 0308-8146
IS - 3
ER -