Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity

Galanal is a novel, competitive inhibitor of the enzyme

Rie Yamamoto, Yasuko Yamamoto, Shinjiro Imai, Ryuta Fukutomi, Yoshio Ozawa, Masako Abe, Yushi Matuo, Kuniaki Saito

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Indoleamine 2,3-dioxygenase (IDO) 1, that catalyzes the first and rate-limiting step in the degradation of L-tryptophan, has an important immunomodulatory function. The activity of IDO1 increases in various inflammatory diseases, including tumors, autoimmune diseases, and different kinds of inflammation. We evaluated the suppressive effect of plant extracts or phytochemicals on IDO1 induction and activity; sixteen kinds of plants extracts and fourteen kinds of phytochemicals were examined. As a result, the methanol extracts of Myoga flower buds, which are traditional Japanese foods, and labdane-type diterpene galanal derived from Myoga flowers significantly suppressed IDO1 activity. The Lineweaver-Burk plot analysis indicated that galanal is a competitive inhibitor. Galanal attenuated L-kynurenine formation with an IC50 value of 7.7 μM in the assay system using recombinant human IDO1, and an IC50 value of 45 nM in the cell-based assay. Further, mechanistic analysis revealed that galanal interfered with the transcriptional function of the nuclear factor-κB and the interferon-γ signaling pathway. These effects of galanal are important for immune response. Because the inhibitory effect of galanal on IDO1 activity was stronger than that of 1-methyl tryptophan, a tryptophan analog, galanal may have great potential as the novel drug for various immune-related diseases.

Original languageEnglish
Article numbere88789
JournalPLoS One
Volume9
Issue number2
DOIs
Publication statusPublished - 12-02-2014
Externally publishedYes

Fingerprint

Indoleamine-Pyrrole 2,3,-Dioxygenase
enzyme inhibitors
Plant Extracts
Phytochemicals
Enzyme Inhibitors
tryptophan
phytopharmaceuticals
Inhibitory Concentration 50
Kynurenine
plant extracts
Tryptophan
inhibitory concentration 50
Diterpenes
Assays
Immune System Diseases
kynurenine
Interferons
Autoimmune Diseases
Methanol
autoimmune diseases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Yamamoto, Rie ; Yamamoto, Yasuko ; Imai, Shinjiro ; Fukutomi, Ryuta ; Ozawa, Yoshio ; Abe, Masako ; Matuo, Yushi ; Saito, Kuniaki. / Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity : Galanal is a novel, competitive inhibitor of the enzyme. In: PLoS One. 2014 ; Vol. 9, No. 2.
@article{7460a6e8ee5a4431abde5eaf301793c5,
title = "Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: Galanal is a novel, competitive inhibitor of the enzyme",
abstract = "Indoleamine 2,3-dioxygenase (IDO) 1, that catalyzes the first and rate-limiting step in the degradation of L-tryptophan, has an important immunomodulatory function. The activity of IDO1 increases in various inflammatory diseases, including tumors, autoimmune diseases, and different kinds of inflammation. We evaluated the suppressive effect of plant extracts or phytochemicals on IDO1 induction and activity; sixteen kinds of plants extracts and fourteen kinds of phytochemicals were examined. As a result, the methanol extracts of Myoga flower buds, which are traditional Japanese foods, and labdane-type diterpene galanal derived from Myoga flowers significantly suppressed IDO1 activity. The Lineweaver-Burk plot analysis indicated that galanal is a competitive inhibitor. Galanal attenuated L-kynurenine formation with an IC50 value of 7.7 μM in the assay system using recombinant human IDO1, and an IC50 value of 45 nM in the cell-based assay. Further, mechanistic analysis revealed that galanal interfered with the transcriptional function of the nuclear factor-κB and the interferon-γ signaling pathway. These effects of galanal are important for immune response. Because the inhibitory effect of galanal on IDO1 activity was stronger than that of 1-methyl tryptophan, a tryptophan analog, galanal may have great potential as the novel drug for various immune-related diseases.",
author = "Rie Yamamoto and Yasuko Yamamoto and Shinjiro Imai and Ryuta Fukutomi and Yoshio Ozawa and Masako Abe and Yushi Matuo and Kuniaki Saito",
year = "2014",
month = "2",
day = "12",
doi = "10.1371/journal.pone.0088789",
language = "English",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity : Galanal is a novel, competitive inhibitor of the enzyme. / Yamamoto, Rie; Yamamoto, Yasuko; Imai, Shinjiro; Fukutomi, Ryuta; Ozawa, Yoshio; Abe, Masako; Matuo, Yushi; Saito, Kuniaki.

In: PLoS One, Vol. 9, No. 2, e88789, 12.02.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity

T2 - Galanal is a novel, competitive inhibitor of the enzyme

AU - Yamamoto, Rie

AU - Yamamoto, Yasuko

AU - Imai, Shinjiro

AU - Fukutomi, Ryuta

AU - Ozawa, Yoshio

AU - Abe, Masako

AU - Matuo, Yushi

AU - Saito, Kuniaki

PY - 2014/2/12

Y1 - 2014/2/12

N2 - Indoleamine 2,3-dioxygenase (IDO) 1, that catalyzes the first and rate-limiting step in the degradation of L-tryptophan, has an important immunomodulatory function. The activity of IDO1 increases in various inflammatory diseases, including tumors, autoimmune diseases, and different kinds of inflammation. We evaluated the suppressive effect of plant extracts or phytochemicals on IDO1 induction and activity; sixteen kinds of plants extracts and fourteen kinds of phytochemicals were examined. As a result, the methanol extracts of Myoga flower buds, which are traditional Japanese foods, and labdane-type diterpene galanal derived from Myoga flowers significantly suppressed IDO1 activity. The Lineweaver-Burk plot analysis indicated that galanal is a competitive inhibitor. Galanal attenuated L-kynurenine formation with an IC50 value of 7.7 μM in the assay system using recombinant human IDO1, and an IC50 value of 45 nM in the cell-based assay. Further, mechanistic analysis revealed that galanal interfered with the transcriptional function of the nuclear factor-κB and the interferon-γ signaling pathway. These effects of galanal are important for immune response. Because the inhibitory effect of galanal on IDO1 activity was stronger than that of 1-methyl tryptophan, a tryptophan analog, galanal may have great potential as the novel drug for various immune-related diseases.

AB - Indoleamine 2,3-dioxygenase (IDO) 1, that catalyzes the first and rate-limiting step in the degradation of L-tryptophan, has an important immunomodulatory function. The activity of IDO1 increases in various inflammatory diseases, including tumors, autoimmune diseases, and different kinds of inflammation. We evaluated the suppressive effect of plant extracts or phytochemicals on IDO1 induction and activity; sixteen kinds of plants extracts and fourteen kinds of phytochemicals were examined. As a result, the methanol extracts of Myoga flower buds, which are traditional Japanese foods, and labdane-type diterpene galanal derived from Myoga flowers significantly suppressed IDO1 activity. The Lineweaver-Burk plot analysis indicated that galanal is a competitive inhibitor. Galanal attenuated L-kynurenine formation with an IC50 value of 7.7 μM in the assay system using recombinant human IDO1, and an IC50 value of 45 nM in the cell-based assay. Further, mechanistic analysis revealed that galanal interfered with the transcriptional function of the nuclear factor-κB and the interferon-γ signaling pathway. These effects of galanal are important for immune response. Because the inhibitory effect of galanal on IDO1 activity was stronger than that of 1-methyl tryptophan, a tryptophan analog, galanal may have great potential as the novel drug for various immune-related diseases.

UR - http://www.scopus.com/inward/record.url?scp=84895769830&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84895769830&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0088789

DO - 10.1371/journal.pone.0088789

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e88789

ER -