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Analysis for Biofunction of Ouabagnin as Endogenous Regulator of Blood Pressure Targeting LXR

Research Project

Project/Area Number 15K01817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Chemical biology
Research InstitutionIwate Medical University (2016-2017)
Tohoku University (2015)

Principal Investigator

TAMURA Satoru  岩手医科大学, 薬学部, 准教授 (30362619)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsウアバゲニン / 肝X受容体 / 生理活性 / 生体分子 / 上皮性ナトリウムチャネル / 集合尿細管細胞 / アグリコン
Outline of Final Research Achievements

Ouabagenin, an aglycone of cardiotonic steroidal glycoside Ouabain, has been thought to be a non-bioactive precursor for biosynthesis of ouabain. In our study, ouabagnin was revealed to show ligandable activity for liver X receptor (LXR). In addition, ouabagenin was disclosed to down-regulate the expression level of epithelial sodium channel (ENaC) on the cells of collecting duct whereas not to lead hepatic steatosis which was normally induced by typical LXR ligands. Thus, ouabagnin is a one of the promising medical seeds as antihypertensive diuretic and useful chemical tool for exploration for LXR. Further investigation is necessary for analysis of the relationship between ouabagenin and ouabain as endogenous factors.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (25 results)

All 2018 2017 2016 2015 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (3 results)

  • [Journal Article] Ouabagenin is a naturally occurring LXR ligand without causing hepatic steatosis as a side effect.2018

    • Author(s)
      Tamura S., Okada M., Kato S., Shinoda Y., Shioda N., Fukunaga K., Ui-Tei K. and Ueda M*.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 2305-2305

    • DOI

      10.1038/s41598-018-20663-z

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] N-Alkylation using sodium triacetoxyborohydride with carboxylic acids as alkyl sources.2018

    • Author(s)
      Tamura, S.; Sato, K.; Kawano, T.
    • Journal Title

      Chem. Pharm. Bull.

      Volume: 66 Pages: 101-103

    • NAID

      130006301037

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 2-substiruted 4,5-dihydro-4-oxo-3-furancarboxylates using acylative intramolecular cyclization of sulfonium salts.2017

    • Author(s)
      Inagaki, S.; Sato, A.; Sato, H.; Tamura, S.; Kawano, T.
    • Journal Title

      Tetrahedron Lett.

      Volume: 58 Issue: 52 Pages: 4872-4875

    • DOI

      10.1016/j.tetlet.2017.11.035

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Helically chiral 1-sulfur-functionalized [6]helicene: synthesis, optical resolution, and functionalization.2017

    • Author(s)
      Tsujihara, T.; Zhou, D.-Y.; Suzuki, T.; Tamura, S.; Kawano, T.
    • Journal Title

      Org. Lett.

      Volume: 19 Issue: 12 Pages: 3311-3314

    • DOI

      10.1021/acs.orglett.7b01470

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 4-halo-3(2H)-furanones using intramolecular cyclization of sulfonium salts.2017

    • Author(s)
      Inagaki, S.; Nakazato, M.; Fukuda, N.; Tamura, S.; Kawano, T.
    • Journal Title

      J. Org. Chem.

      Volume: 82 Issue: 11 Pages: 5583-5589

    • DOI

      10.1021/acs.joc.7b00399

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The plant cell-wall enzyme AtXTH3 catalyses covalent cross-linking between cellulose and cello-oligosaccharide2017

    • Author(s)
      Shinohara, N.; Sunagawa, N.; Tamura, S.; Yokoyama, R.; Ueda, M.; Igarashi, K.; Nishitani, K.
    • Journal Title

      Sci. Rep.

      Volume: 7 Issue: 1 Pages: 46099-46099

    • DOI

      10.1038/srep46099

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Functional importance of the sugar moiety of jasmonic acid glucoside for bioactivity and target affinity.2015

    • Author(s)
      Ueda, M.; Yang, G.; Nukadzuka, Y.; Ishimaru, Y.; Tamura, S.; Manabe, Y.
    • Journal Title

      Org. Biomol. Chem.

      Volume: 13 Issue: 1 Pages: 55-58

    • DOI

      10.1039/c4ob02106a

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 核内受容体LXR新規アゴニストの作用と可能性2018

    • Author(s)
      米澤 正、中村朱里、田村 理、川崎 靖、杉山晶規、名取泰博
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ビスヘリセン型ジスルホンイミドの合成2018

    • Author(s)
      辻原哲也、遠藤沙耶香、嵩原綱吉、周 大楊、鈴木健之、田村 理、河野富一
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] スルホニウム塩のアシル化/分子内環化反応を利用した2置換4,5-ジヒドロ-4-オキソ-3-フランカルボン酸エステルの合成2018

    • Author(s)
      稲垣 祥、佐藤朱里、佐藤 遥、田村 理、河野富一
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血管新生阻害活性を示す真菌由来ブテノリド類の構造活性相関2018

    • Author(s)
      田村 理、吉田有毅、荒井雅吉、中村友香、小林資正、河野富一
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 血管新生阻害活性を示す真菌由来ポリケチドおよび立体異性体の合成2017

    • Author(s)
      田村 理、荒井雅吉、中村友香、小林資正、河野富一
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 水素化ホウ素系試薬を用いたカルボン酸による新規なN-アルキル化反応2017

    • Author(s)
      田村 理、佐藤圭悟、河野富一
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      横浜
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Trial for Searching Drug-Seeds from Natural Resources2017

    • Author(s)
      田村 理
    • Organizer
      平成29年度化学系学協会東北大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 真菌由来血管新生阻害ブテノライド類の構造活性相関研究2017

    • Author(s)
      田村 理、荒井雅吉、中村友香、小林資正、河野富一
    • Organizer
      日本ケミカルバイオロジー学会 第12回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 1位硫黄官能基化[6]ヘリセンの合成、光学分割および官能基化2017

    • Author(s)
      辻原哲也、遠藤沙耶香、佐々木歩美、山高裕毅、周 大楊、鈴木健之、田村 理、河野富一
    • Organizer
      第43回反応と合成の進歩シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 1位硫黄官能基化[6]ヘリセンを基盤とする有機分子触媒の創薬研究2017

    • Author(s)
      辻原哲也、遠藤沙耶香、嵩原綱吉、周 大楊、鈴木健之、田村 理、河野富一
    • Organizer
      第10回有機触媒シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪肝を誘導しない新奇なLXRリガンドとして機能するウアバゲニン2016

    • Author(s)
      田村 理, 岡田 麻衣子、 篠田 康晴, 塩田 倫史, 福永 浩司, 大石 悠, 上田 実
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Research-status Report
  • [Presentation] シロイヌナズナのキシログルカン転移酵素・加水分解酵素ファミリータンパク質によるセルロース性多糖への糖転移反応2016

    • Author(s)
      篠原 直貴,砂川 直輝,田村 理,横山 隆亮,五十嵐 圭日子,上田 実,西谷 和彦
    • Organizer
      第57回植物生理学会
    • Place of Presentation
      盛岡
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Elucidation for bioactivity of ouabagenin, a presumed endogenous ligand for nuclear receptor2015

    • Author(s)
      Tamura, S.; Oishi, H.; Abe, T.; Okada, M.; Ueda, M.
    • Organizer
      PacifiChem2015
    • Place of Presentation
      Honolulu
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 核内受容体内在性リガンドとしてのウアバゲニンの機能解析2015

    • Author(s)
      田村理 、大石悠 、阿部哲郎 、岡田麻衣子、上田実
    • Organizer
      日本ケミカルバイオロジー学会第10回年会
    • Place of Presentation
      仙台
    • Year and Date
      2015-06-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 核内受容体を介したウアバゲニンの機能解析2015

    • Author(s)
      大石 悠、田村 理、阿部 哲郎、岡田 麻衣子、上田 実
    • Organizer
      第26回万有仙台シンポジウム
    • Place of Presentation
      仙台
    • Year and Date
      2015-06-06
    • Related Report
      2015 Research-status Report
  • [Remarks] 既知医薬資源から新たな高血圧治療薬シーズを発見 糖を外すと作用が変わる?

    • URL

      http://www.sci.tohoku.ac.jp/news/20180202-9504.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 既知医薬資源から新たな高血圧治療薬シーズを発見~砂糖をはずすと作用が変わる?

    • URL

      http://www.iwate-med.ac.jp/news/n5-research/kikaku-180216/

    • Related Report
      2017 Annual Research Report
  • [Remarks] ステロイド配糖体アグリコンをベースとした 新規生理活性物質の探索

    • URL

      http://www.orgchem1.chem.tohoku.ac.jp/orgchem1/Research_4.html

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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