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Elucidation of molecular mechanism of functional foods for physiological role via conjugation-deconjugation process of dietary compounds

Research Project

Project/Area Number 18H02159
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionToyama Prefectural University

Principal Investigator

Ikushiro Shinichi  富山県立大学, 工学部, 教授 (50244679)

Co-Investigator(Kenkyū-buntansha) 戸田 弘  富山県立大学, 工学部, 講師 (60608321)
伊藤 伸哉  富山県立大学, 工学部, 教授 (90213066)
西川 美宇  富山県立大学, 工学部, 助教 (90749805)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsポリフェノール / 抱合代謝物 / 出芽酵母 / UDP-グルクロン-酸転移酵素 / 硫酸転移酵素 / 腸内細菌 / 脱抱合 / グルクロニダーゼ / ポリフェノール動態 / グルクロン酸抱合 / 硫酸抱合 / 加水分解酵素 / フラボノイド / 酵母 / UDP-グルクロン酸転移酵素
Outline of Final Research Achievements

Most of functional ingredients out of the food are confined to the living body as some metabolites, but the details of the onset of function mechanism as the metabolites are not clarified. In this study, enzyme-based synthetic platform of flavonoid conjugates were established using xenobiotic metabolizing enzymes-expressing budding yeast cell. Conjugates of several polyphenol were synthesized to glucuronides, sulfates, and methyl conjugates necessary for elucidation of molecular mechanism of functional foods for physiological role via conjugation-deconjugation process of dietary compounds.

Academic Significance and Societal Importance of the Research Achievements

フラボノイドなどの食品中機能性成分が示す生理作用は医薬品の代替成分として注目されているが、これら化合物は生体にとっては異物であり生体利用率が低く体内への吸収は極めて低い。体内にとどまる形態としては抱合体であることが近年明らかとなり、抱合体における機能性成分の効果発現の科学的エビデンス確立が求められている。本研究成果は生体における低分子化合物に対する異物代謝の分子基盤の解明につながるとともに、ヒトを含めた生物に対する食品中機能性成分の作用機序解明にも貢献するものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (32 results)

All 2021 2020 2019 2018

All Journal Article (18 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Pharmacokinetics and metabolism of cinnamic acid derivatives and flavonoids after oral administration of Brazilian green propolis in humans2021

    • Author(s)
      Yamaga Masayuki、Tani Hiroko、Nishikawa Miyu、Fukaya Keisuke、Ikushiro Shin-ichi、Murota Kaeko
    • Journal Title

      Food & Function

      Volume: 12 Issue: 6 Pages: 2520-2530

    • DOI

      10.1039/d0fo02541k

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 異物代謝酵素発現酵母を用いた代謝物合成法の開発:医薬品および機能性食品開発における代謝研究への活用2021

    • Author(s)
      西川美宇・生城真一 榊利之
    • Journal Title

      化学と生物

      Volume: 59 Pages: 84-90

    • NAID

      130008149771

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Identification and in silico prediction of metabolites of tebufenozide derivatives by major human cytochrome P450 isoforms2020

    • Author(s)
      Edamatsu Hiroaki、Yagawa Masataka、Ikushiro Shinichi、Sakaki Toshiyuki、Nakagawa Yoshiaki、Miyagawa Hisashi、Akamatsu Miki
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 28 Issue: 9 Pages: 115429-115429

    • DOI

      10.1016/j.bmc.2020.115429

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hetero-oligomer formation of mouse UDP-glucuronosyltransferase (UGT) 2b1 and 1a1 results in the gain of glucuronidation activity towards morphine, an activity which is absent in homo-oligomers of either UGT2020

    • Author(s)
      Miyauchi Yuu、Kurita Ayumi、Yamashita Ryohei、Takamatsu Tomoyuki、Ikushiro Shin’ichi、Mackenzie Peter I.、Tanaka Yoshitaka、Ishii Yuji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 525 Issue: 2 Pages: 348-353

    • DOI

      10.1016/j.bbrc.2020.02.075

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of novel genetically modified rats to reveal the molecular mechanisms of vitamin D actions.2020

    • Author(s)
      Nishikawa M, Yasuda K, Takamatsu M, Abe K, Okamoto K, Horibe K, Mano H, Nakagawa K, Tsugawa N, Hirota Y, Horie T, Hinoi E, Okano T, Ikushiro S, Sakaki T.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 5677-5677

    • DOI

      10.1038/s41598-020-62048-1

    • NAID

      130008108985

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Whole-cell dependent biosynthesis of N- and S-oxides using human flavin containing monooxygenases expressing budding yeast2020

    • Author(s)
      Masuyama Yuuka、Nishikawa Miyu、Yasuda Kaori、Sakaki Toshiyuki、Ikushiro Shinichi
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 35 Issue: 3 Pages: 274-280

    • DOI

      10.1016/j.dmpk.2020.01.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic variants of UDP-glucuronosyltransferases 1A1, 1A6, and 1A9 in cynomolgus and rhesus macaques2020

    • Author(s)
      Uno Yasuhiro、Mikami Takahiro、Tsukazaki Yasuko、Nakanishi Yasuharu、Murayama Norie、Ikushiro Shinichi、Tsusaki Hideshi、Yamazaki Hiroshi
    • Journal Title

      Xenobiotica

      Volume: 51 Issue: 1 Pages: 115-121

    • DOI

      10.1080/00498254.2020.1810367

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 異物代謝酵素発現酵母を用いたポリフェノール抱合代謝物調製技術の開発2020

    • Author(s)
      生城真一、増山優香、西川美宇、安田佳織、榊利之
    • Journal Title

      日本ポリフェノール学会誌

      Volume: 9 Pages: 13-18

    • NAID

      40022319694

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Molecular characterization of functional UDP-glucuronosyltransferases 1A and 2B in common marmosets2020

    • Author(s)
      Uno Yasuhiro、Uehara Shotaro、Inoue Takashi、Kawamura Shu、Murayama Norie、Nishikawa Miyu、Ikushiro Shinichi、Sasaki Erika、Yamazaki Hiroshi
    • Journal Title

      Biochemical Pharmacology

      Volume: 172 Pages: 113748-113748

    • DOI

      10.1016/j.bcp.2019.113748

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynamics of the Cellular Metabolism of Leptosperin Found in Manuka Honey2019

    • Author(s)
      Kato Yoji、Kawai Masaki、Kawai Shota、Okano Yayako、Rokkaku Natsumi、Ishisaka Akari、Murota Kaeko、Nakamura Toshiyuki、Nakamura Yoshimasa、Ikushiro Shinichi
    • Journal Title

      Journal of Agricultural and Food Chemistry

      Volume: 67 Issue: 39 Pages: 10853-10862

    • DOI

      10.1021/acs.jafc.9b03894

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional and molecular characterization of UDP-glucuronosyltransferase 2 family in cynomolgus macaques2019

    • Author(s)
      Uno Yasuhiro、Takahira Rika、Murayama Norie、Onozeki Shunsuke、Kawamura Shu、Uehara Shotaro、Ikenaka Yoshinori、Ishizuka Mayumi、Ikushiro Shinichi、Yamazaki Hiroshi
    • Journal Title

      Biochemical Pharmacology

      Volume: 163 Pages: 335-344

    • DOI

      10.1016/j.bcp.2019.03.002

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sulfate conjugates are the major metabolites in rats administrated with sesamin2019

    • Author(s)
      Yasuda Kaori、Okamoto Kairi、Ueno Sera、Itoh Kasumi、Nishikawa Miyu、Ikushiro Shinichi、Sakaki Toshiyuki
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 34 Issue: 2 Pages: 134-140

    • DOI

      10.1016/j.dmpk.2018.12.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive Analyses of Quercetin Conjugates by LC/MS/MS Revealed That Isorhamnetin-7-O-glucuronide-4′-O-sulfate Is a Major Metabolite in Plasma of Rats Fed with Quercetin Glucosides2019

    • Author(s)
      Tanaka Seiya、Trakooncharoenvit Aphichat、Nishikawa Miyu、Ikushiro Shinichi、Hara Hiroshi
    • Journal Title

      Journal of Agricultural and Food Chemistry

      Volume: 67 Issue: 15 Pages: 4240-4249

    • DOI

      10.1021/acs.jafc.8b06929

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lymphatic metabolites of quercetin after intestinal administration of quercetin-3-glucoside and its aglycone in rats2018

    • Author(s)
      Nakamura T, Kinjo C, Nakamura Y, Kato Y, Nishikawa M, Hamada M, Nakajima N, Ikushiro S, Murota K.
    • Journal Title

      Arch Biochem Biophys.

      Volume: 645 Pages: 126-136

    • DOI

      10.1016/j.abb.2018.03.024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Microbial production of novel sulphated alkaloids for drug discovery2018

    • Author(s)
      Matsumura E., Nakagawa A., Tomabechi Y., Ikushiro S., Sakaki T., Katayama T., Yamamoto K., Kumagai H., Sato F. and Minami H.
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-018-26306-7

    • NAID

      120006517899

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Limited expression of functional cytochrome p450 2c subtypes in the liver and small intestine of domestic cats2018

    • Author(s)
      Ono Yuka、Sugiyama Souta、Matsushita Mayu、Kitazawa Takio、Amano Tomoko、Uno Yasuhiro、Ikushiro Shinichi、Teraoka Hiroki
    • Journal Title

      Xenobiotica

      Volume: 49 Issue: 6 Pages: 627-635

    • DOI

      10.1080/00498254.2018.1483543

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous collection of the portal and superior vena cava blood in conscious rats defined that intestinal epithelium is the major site of glucuronidation, but not sulfation and methylation, of quercetin2018

    • Author(s)
      Tanaka Seiya、Oyama Manami、Nishikawa Miyu、Ikushiro Shinichi、Hara Hiroshi
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 82 Issue: 12 Pages: 2118-2129

    • DOI

      10.1080/09168451.2018.1515615

    • NAID

      120006769943

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular and functional characterization of UDP-glucuronosyltransferase 1A in cynomolgus macaques.2018

    • Author(s)
      Uno, Y., Takahira, R., Murayama, N., Ishii, Y., Ikenaka, Y., Ishizuka, M., Yamazaki, H., and Ikushiro, S.
    • Journal Title

      Biochem. Pharmacol.

      Volume: 155 Pages: 172-181

    • DOI

      10.1016/j.bcp.2018.06.027

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 抱合酵素発現酵母菌体を用いた食品中機能性成分抱合代謝物の網羅的合成2020

    • Author(s)
      中山舞、西川美宇、深谷圭介、占部大介、榊利之、生城真一
    • Organizer
      2020年度日本フードファクター学会・日本農芸化学会西日本支部合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 活性化マクロファージにおけるケルセチン抱合代謝物の機能性2020

    • Author(s)
      西川美宇、加田 ゆり子、木全未来、松村美咲、榊利之、生城真一
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 異物代謝酵素発現酵母を用いたスチルべノイド抱合代謝物の網羅的合成2020

    • Author(s)
      中山舞、西川美宇、深谷圭介、占部大介、榊利之、生城真一
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 植物フィトケミカル及びその代謝物による コロナウイルス3CLプロテアーゼ阻害2020

    • Author(s)
      加藤陽二、焼本千里、伊藤美紀子、辻一徳、丹羽利夫、西川 美宇、生城真一
    • Organizer
      日本農芸化学会2021年度大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 異物抱合酵素発現酵母を用いたスチルベン化合物の抱合反応解析及び抱合体調製2019

    • Author(s)
      4)中山舞、西川美宇、安田佳織、鎌倉昌樹、深谷圭介、占部大介、榊利之、生城真一
    • Organizer
      日本ビタミン学会第71回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] LC/MS/MSを用いた血中ケルセチン抱合体の網羅的分析2019

    • Author(s)
      田中 誠也,西川 美宇, 生城 真一, 原 博
    • Organizer
      日本食品科学工学会第66回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Biosynthesis of hetro-conjugates of quercetin using xenobiotic enzymes expressing yeast2019

    • Author(s)
      11)S. Ikushiro, M. Nishikawa, K. Yasuda, T. Sakaki
    • Organizer
      ICoFF2019/ISNFF2019/ICPH2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Whole cell-dependent preparation of 8-prenylnaringenin glucuronides using UDP-glucuronosyltransferase expressing yeast2019

    • Author(s)
      12)M. Kitami, R. Mukai, M. Nishikawa, K. Fukaya, D. Urabe, T. Sakaki, S. Ilushiro
    • Organizer
      ICoFF2019/ISNFF2019/ICPH2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 出芽酵母発現系を用いた植物由来グルクロン酸転移酵素による抱合体合成技術の開発2019

    • Author(s)
      橋朋花、西川美宇、安田佳織、榊利之、生城真一
    • Organizer
      第13回日本ポリフェノール学会・第16回日本カテキン学会合同学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Bone marrow-derived macrophage (BMDM)におけるケルセチングルクロン酸抱合体による抗炎症効果の検証2018

    • Author(s)
      山之内祐香・加田ゆり子・西川美宇・古澤之裕・榊利之・生城真一
    • Organizer
      日本生化学会北陸支部第36回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 薬物代謝酵素発現酵母を用いた医薬品および食品成分の代謝予測と代謝物調製法の確立2018

    • Author(s)
      西川美宇,増山優香,安田佳織,濱田昌弘,中島範行,榊利之,生城真
    • Organizer
      日本毒性学会医薬品毒性機序研究部会 第1回医薬品毒性機序研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウスマクロファージ由来RAW264.7細胞におけるケルセチングルクロン酸抱合体の代謝解析および活性評価.2018

    • Author(s)
      西川美宇, 加田ゆり子, 山之内佑香, 榊利之, 生城真一.
    • Organizer
      日本フードファクター学会第23回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 異物抱合酵素発現酵母菌体を用いたスチルベン化合物の抱合反応の解析2018

    • Author(s)
      中山舞・西川美宇・安田佳織・鎌倉昌樹・榊利之・生城真一
    • Organizer
      日本フードファクター学会第23回学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Construction of yeast expression system for drug-metabolizing enzymes and its application to preparative production of drug metabolites.2018

    • Author(s)
      Miyu Nishikawa, Yuuka Masuyama, Kaori Yasuda, Toshiyuki Sakaki, Shinichi Ikushiro.
    • Organizer
      2018 International Meeting on 22nd MDO and 33rd JSSX.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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