Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.

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 inflamma...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Rie Yamamoto, Yasuko Yamamoto, Shinjiro Imai, Ryuta Fukutomi, Yoshio Ozawa, Masako Abe, Yushi Matuo, Kuniaki Saito
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2014
Materias:
R
Q
Acceso en línea:https://doaj.org/article/441c932796114eb791e97a06a3bfc07a
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:441c932796114eb791e97a06a3bfc07a
record_format dspace
spelling oai:doaj.org-article:441c932796114eb791e97a06a3bfc07a2021-11-18T08:32:45ZEffects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.1932-620310.1371/journal.pone.0088789https://doaj.org/article/441c932796114eb791e97a06a3bfc07a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24533148/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Indoleamine 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.Rie YamamotoYasuko YamamotoShinjiro ImaiRyuta FukutomiYoshio OzawaMasako AbeYushi MatuoKuniaki SaitoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e88789 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rie Yamamoto
Yasuko Yamamoto
Shinjiro Imai
Ryuta Fukutomi
Yoshio Ozawa
Masako Abe
Yushi Matuo
Kuniaki Saito
Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.
description 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.
format article
author Rie Yamamoto
Yasuko Yamamoto
Shinjiro Imai
Ryuta Fukutomi
Yoshio Ozawa
Masako Abe
Yushi Matuo
Kuniaki Saito
author_facet Rie Yamamoto
Yasuko Yamamoto
Shinjiro Imai
Ryuta Fukutomi
Yoshio Ozawa
Masako Abe
Yushi Matuo
Kuniaki Saito
author_sort Rie Yamamoto
title Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.
title_short Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.
title_full Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.
title_fullStr Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.
title_full_unstemmed Effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.
title_sort effects of various phytochemicals on indoleamine 2,3-dioxygenase 1 activity: galanal is a novel, competitive inhibitor of the enzyme.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/441c932796114eb791e97a06a3bfc07a
work_keys_str_mv AT rieyamamoto effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
AT yasukoyamamoto effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
AT shinjiroimai effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
AT ryutafukutomi effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
AT yoshioozawa effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
AT masakoabe effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
AT yushimatuo effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
AT kuniakisaito effectsofvariousphytochemicalsonindoleamine23dioxygenase1activitygalanalisanovelcompetitiveinhibitoroftheenzyme
_version_ 1718421618088214528