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Study on physiological role of sulfation metabolism: challenges on the synthesis of phenolic sulfates and functional evaluation

Research Project

Project/Area Number 20K05881
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 38050:Food sciences-related
Research InstitutionTokai University

Principal Investigator

Yasuda Shin  東海大学, 農学部, 教授 (10512923)

Co-Investigator(Kenkyū-buntansha) 小野 政輝  東海大学, 農学部, 教授 (60177269)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2020: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords硫酸化 / フェノール性硫酸体 / 代謝物 / 合成 / 機能性評価
Outline of Research at the Start

生体内における硫酸化は、生理活性物質や外来異物の代謝変換と活性調節を担う主要な代謝抱合反応の一つである。様々な硫酸化代謝物の入手が容易ではない現状のもと、本課題ではポリフェノール等のフェノール性硫酸化代謝物の合成法の開発を行い、硫酸化代謝物の生理機能の有無や前駆体との活性差異を試験管ならびに培養細胞レベルで定量的に明らかにする。硫酸化代謝を主軸に機能性研究を推進する。

Outline of Final Research Achievements

Sulfation has been generally thought to play a role in the metabolism and inactivation of target compounds; however, the extent of this process has been unclear for individual compounds. In this study, we successfully synthesized the sulfated form of acetaminophen (APAPS) and investigated its antioxidant activity compared to that of the parent compound APAP, an antipyretic and analgesic drug. The results showed that while the antioxidant activity of APAPS was lower than that of APAP, both p-aminophenol and its sulfate, analogous compounds to APAP, exhibited comparable activity. Collectively, we concluded that sulfation may not always lead to the inactivation of target compound(s).

Academic Significance and Societal Importance of the Research Achievements

従来、硫酸化は異物代謝と排泄の面のみで考えられがちであった。本研究では、一部のフェノール性化合物を例に有機合成を試み、更に生理活性の増減や減弱に、硫酸化がどの程度貢献しているのかを明らかにした。本研究で得られた成果により、将来的には硫酸化代謝後の化合物の効能を予測するための基礎となる可能性がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (28 results)

All 2024 2023 2022 2021 2020 Other

All Int'l Joint Research (3 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 5 results) Presentation (14 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (5 results)

  • [Int'l Joint Research] The University of Toledo(米国)

    • Related Report
      2022 Research-status Report
  • [Int'l Joint Research] The University of Toledo(米国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] The University of Toledo(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] (総説) 第2相薬物代謝における硫酸抱合体の抗酸化活性研究2024

    • Author(s)
      安田伸, 黒木勝久, 榊原陽一, 水光正仁
    • Journal Title

      東海大学先進生命科学研究所紀要

      Volume: 8 Pages: 5-10

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 高速液体クロマトグラフィーを用いたアセトアミノフェンO-硫酸体とチロシンO-硫酸体のUV検出による測定法2023

    • Author(s)
      森田千紘, 元山優作, 谷口玲央真, 上田裕人, 木下英樹, 小野政輝, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Journal Title

      東海大学紀要農学部

      Volume: 42 Pages: 1-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of radical scavenging effects of acetaminophen, <i>p</i>-aminophenol and their <i>O</i><i>-</i>sulfated conjugates2022

    • Author(s)
      Morita Chihiro、Tokunaga Yuki、Ueda Yuto、Ono Masateru、Kinoshita Hideki、Kurogi Katsuhisa、Sakakibara Yoichi、Suiko Masahito、Liu Ming-Cheh、Yasuda Shin
    • Journal Title

      The Journal of Toxicological Sciences

      Volume: 47 Issue: 10 Pages: 421-428

    • DOI

      10.2131/jts.47.421

    • ISSN
      0388-1350, 1880-3989
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acetaminophen硫酸体の有機合成2022

    • Author(s)
      森田千紘, 谷口玲央真, 吉田実央, 德永祐希, 木下英樹, 小野政輝, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Journal Title

      東海大学紀要農学部

      Volume: 41 Pages: 39-46

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] SULT genetic polymorphisms: physiological, pharmacological and clinical implications2021

    • Author(s)
      Kurogi Katsuhisa、Rasool Mohammed I.、Alherz Fatemah A.、El Daibani Amal A.、Bairam Ahsan F.、Abunnaja Maryam S.、Yasuda Shin、Wilson Lauren J.、Hui Ying、Liu Ming-Cheh
    • Journal Title

      Expert Opinion on Drug Metabolism & Toxicology

      Volume: 17 Issue: 7 Pages: 767-784

    • DOI

      10.1080/17425255.2021.1940952

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of indole and indoxyl on the intracellular oxidation level and phagocytic activity of differentiated HL-60 human macrophage cells.2020

    • Author(s)
      Tsutsumi S, Tokunaga Y, Shimizu S, Kinoshita H, Ono M, Kurogi K, Sakakibara Y, Suiko M, Liu M-C, Yasuda S.
    • Journal Title

      J Toxicol Sci

      Volume: 45 Issue: 9 Pages: 569-579

    • DOI

      10.2131/jts.45.569

    • NAID

      130007895031

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] U937ヒト分化マクロファージの細胞内酸化レベルと貪食能に及ぼすIndoxyl Sulfateの影響とその制御2023

    • Author(s)
      岩本若菜, 池田知弘, 西川大貴, 上田裕人, 平野将司, 小野政輝, 木下英樹, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Organizer
      第60回化学関連支部合同九州大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Acetaminophen、p-AminophenolとそれらのO-硫酸体の抗酸化活性:構造上の他の類似化合物との比較2023

    • Author(s)
      安田伸, 森田千紘, 岩本若菜, 上田裕人, 小野政輝, 木下英樹, 黒木勝久, 榊原陽一, 水光正仁
    • Organizer
      第60回化学関連支部合同九州大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Investigation of antioxidant activities of Phase-II sulfated compounds2023

    • Author(s)
      Shin Yasuda
    • Organizer
      2023 International Joint Meeting of the 23rd International Conference on Cytochrome P450 and the 38th Annual Meeting of the Japanese Society for the Study of Xenobiotics [2023 ICCP/JSSX]
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Tryptophan由来Indoxyl SulfateがU937ヒト分化マクロファージ細胞に及ぼす影響と抗酸化剤による制御2023

    • Author(s)
      岩本若菜, 池田知弘, 西川大貴, 澄川碧緯, 上田裕人, 平野将司, 小野政輝, 木下英樹, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Organizer
      令和5年度(2023年度)日本食品科学工学会西日本支部大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Determination of acetaminophen O-sulfate and tyrosine O-sulfate by high-performance liquid chromatography with UV detection2023

    • Author(s)
      Yasuda S, Morita C, Motoyama Y, Ikemura N, Shiozawa H, Ueda Y, Kinoshita H, Ono M.
    • Organizer
      The 19th Asian Agricultural Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of p-cresyl sulfate on the intracellular oxidation levels of HL-60-differentiated macrophage cells under oxidative stress: concerted actions with hydrogen peroxide and nitric oxide2023

    • Author(s)
      Ikeda T, Iwamoto W, Nishikawa H, Seo Y, Goto Y, Ueda Y, Hirano M, Kinoshita H, Ono M, Yasuda S.
    • Organizer
      The 19th Asian Agricultural Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] On the suppression of HL-60 human leukocyte cell growth by indoxyl sulfate: regulatory effect with a representative antioxidant, Trolox2023

    • Author(s)
      Iwamoto W, Sumikawa A, Goto Y, Seo Y, Ikeda T, Nishikawa H, Ueda Y, Hirano M, Ono M, Kinoshita H, Yasuda S
    • Organizer
      The 19th Asian Agricultural Symposium
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトマクロファージ細胞モデルを用いた貪食作用に及ぼす尿毒素インドキシル硫酸の影響2022

    • Author(s)
      安田伸, 堤秀平, 森田千紘, 岩本若菜, 上田裕人, 木下英樹, 小野政輝, 黒木勝久, 榊原陽一, 水光正仁.
    • Organizer
      第59回化学関連支部合同九州大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Acetaminophen、p-Aminophenolとそれら硫酸体の抗酸化活性の比較評価2022

    • Author(s)
      森田千紘, 德永祐希, 上田裕人, 木下英樹, 小野政輝, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Organizer
      第59回化学関連支部合同九州大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 937ヒト分化マクロファージの細胞内酸化レベルと貪食能に及ぼす硫酸化代謝物Indoxyl Sulfateの影響2022

    • Author(s)
      岩本若菜, 森田千紘, 瀬尾優太, 後藤優貴, 上田裕人, 平野将司, 小野政輝, 木下英樹, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Organizer
      日本農芸化学会2022年度西日本支部大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Acetaminophen、p-AminophenolとそれらのO-硫酸体の抗酸化活性の比較2022

    • Author(s)
      森田千紘, 德永祐希, 谷口玲央真, 元山優作, 岩本若菜, 上田裕人, 小野政輝, 木下英樹, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Organizer
      日本農芸化学会2022年度西日本支部大会
    • Related Report
      2022 Research-status Report
  • [Presentation] Acetaminophen硫酸体の合成と真正性の検証2021

    • Author(s)
      森田千紘, 谷口玲央真, 吉田実央, 德永祐希, 木下英樹, 小野政輝, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Organizer
      令和3年度 日本栄養食糧学会九州沖縄支部大会
    • Related Report
      2021 Research-status Report
  • [Presentation] Acetaminophen硫酸体合成法の検討2021

    • Author(s)
      森田千紘, 原口和也, 吉田実央, 德永祐希, 堤秀平, 上田裕人, 木下英樹, 小野政輝, 黒木勝久, 榊原陽一, 水光正仁, 安田伸
    • Organizer
      日本農芸化学会西日本支部ほか化学関連支部共催, 第58回化学関連支部合同九州大会
    • Related Report
      2021 Research-status Report
  • [Presentation] ヒトマクロファージ細胞モデルを用いた尿毒素インドキシル硫酸の細胞内酸化レベルに及ぼす影響2021

    • Author(s)
      安田伸, 堤秀平, 森田千紘, 上田裕人, 木下英樹, 小野政輝, 黒木勝久, 榊原陽一, 水光正仁
    • Organizer
      日本農芸化学会西日本支部ほか化学関連支部共催, 第58回化学関連支部合同九州大会
    • Related Report
      2021 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      https://sites.google.com/view/shokuki2525

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Remarks] 大学HP 農学部食生命科学科の安田教授が国際会議のシンポジウムで講演(2023.10.03)

    • URL

      https://www.u-tokai.ac.jp/news-campus/663206/

    • Related Report
      2023 Annual Research Report
  • [Remarks] (大学のホームページ ニュース掲載)

    • Related Report
      2023 Annual Research Report
  • [Remarks] 大学のホームページ ニュース掲載

    • URL

      https://www.u-tokai.ac.jp/news-campus/245852/

    • Related Report
      2022 Research-status Report
  • [Remarks] 研究室ホームページ (Lab Website)

    • URL

      https://sites.google.com/view/shokuki2525

    • Related Report
      2021 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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