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.
authors.affiliation: Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto-City, Kyoto, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto-City, Kyoto, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Graduate School of Nutrition and Environmental Sciences, University of Shizuoka, Shizuoka-City, Shizuoka, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Imai
authors.affiliation: Health Care Research Center, Nisshin Pharma Inc., Chiyoda-ku, Tokyo, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Fukutomi
authors.affiliation: Health and Nutrition, Takasaki University of Health and Welfare, Takasaki-City, Gunma, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Health and Nutrition, Takasaki University of Health and Welfare, Takasaki-City, Gunma, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Abe
authors.affiliation: Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto-City, Kyoto, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Matuo
authors.affiliation: Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto-City, Kyoto, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Saito
mesh_terms: D004224:Diterpenes / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007700:Kinetics; D016328:NF-kappa B / Q000378:metabolism; D064209:Phytochemicals / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D016328:NF-kappa B; D064209:Phytochemicals; D010936:Plant Extracts; D007371:Interferon-gamma