Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols

Suengmok Cho; Hyejin Yang; You Jin Jeon; C. Justin Lee; Young Ho Jin; Nam In Baek; Dongsoo Kim; Sung Myung Kang; Minseok Yoon; Heim Yong; Makoto Shimizu; Daeseok Han

doi:10.1016/j.foodchem.2011.08.040

Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols

Suengmok Cho, Hyejin Yang, You Jin Jeon, C. Justin Lee, Young Ho Jin, Nam In Baek, Dongsoo Kim, Sung Myung Kang, Minseok Yoon, Heim Yong, Makoto Shimizu, Daeseok Han

KU-KIST Graduate School of Converging Science and Technology

Research output: Contribution to journal › Article › peer-review

56 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1133-1142
Number of pages	10
Journal	Food Chemistry
Volume	132
Issue number	3
DOIs	https://doi.org/10.1016/j.foodchem.2011.08.040
Publication status	Published - 2012 Jun 1

Keywords

Ecklonia cava Kjellman
Edible seaweeds
GABA type A-benzodiazepine receptor
Hypnotic activity
Phlorotannin

ASJC Scopus subject areas

Analytical Chemistry
Food Science

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Cho, S., Yang, H., Jeon, Y. J., Lee, C. J., Jin, Y. H., Baek, N. I., Kim, D., Kang, S. M., Yoon, M., Yong, H., Shimizu, M., & Han, D. (2012). Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols. Food Chemistry, 132(3), 1133-1142. https://doi.org/10.1016/j.foodchem.2011.08.040

Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor : A novel neurological activity of seaweed polyphenols. / Cho, Suengmok; Yang, Hyejin; Jeon, You Jin et al.

In: Food Chemistry, Vol. 132, No. 3, 01.06.2012, p. 1133-1142.

Research output: Contribution to journal › Article › peer-review

Cho, S, Yang, H, Jeon, YJ, Lee, CJ, Jin, YH, Baek, NI, Kim, D, Kang, SM, Yoon, M, Yong, H, Shimizu, M & Han, D 2012, 'Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols', Food Chemistry, vol. 132, no. 3, pp. 1133-1142. https://doi.org/10.1016/j.foodchem.2011.08.040

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title = "Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols",

abstract = "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.",

keywords = "Ecklonia cava Kjellman, Edible seaweeds, GABA type A-benzodiazepine receptor, Hypnotic activity, Phlorotannin",

author = "Suengmok Cho and Hyejin Yang and Jeon, {You Jin} and Lee, {C. Justin} and Jin, {Young Ho} and Baek, {Nam In} and Dongsoo Kim and Kang, {Sung Myung} and Minseok Yoon and Heim Yong and Makoto Shimizu and Daeseok Han",

note = "Funding Information: This study was supported by a grant from the Korea Food Research Institute (Project No. E0112402). The first author wishes to thank the Japanese Society for Promotion of Science (JSPS) for a RONPAKU (Dissertation Ph.D. program) Fellowship at the Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo.",

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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

N1 - Funding Information: This study was supported by a grant from the Korea Food Research Institute (Project No. E0112402). The first author wishes to thank the Japanese Society for Promotion of Science (JSPS) for a RONPAKU (Dissertation Ph.D. program) Fellowship at the Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo.

PY - 2012/6/1

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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.

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Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols

Abstract

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