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Exploratory research on prenyl derivatives with anti-glycation and anti-periodontopathogenic activity to prevent and ameliorate periodontal disease-related conditions.

Research Project

Project/Area Number 20K07122
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47050:Environmental and natural pharmaceutical resources-related
Research InstitutionSojo University

Principal Investigator

Ikeda Tsuyoshi  崇城大学, 薬学部, 教授 (80295138)

Co-Investigator(Kenkyū-buntansha) 中尾 龍馬  国立感染症研究所, 細菌第一部, 主任研究官 (10370959)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2023: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords歯周病 / 糖化 / Porphyromonas gingivalis / CMA / プレニル誘導体 / ポリフェノール / コラーゲン / AGEs / 歯周病菌 / 糖化最終生成物 / カレーリーフ / ノブドウ / プレニル化四環カルバゾールアルカロイド / mahanimbine / (-)-catechin / quercetinラムノース配糖体 / ウィキョウ / ペトロセリン酸 / プレニルフラボノイド / ホップ / グリーンルイボス / ウイキョウ / 食品素材 / 歯周病原菌
Outline of Research at the Start

歯周病は口腔のみならず、糖尿病や動脈硬化症などの全身疾患の誘因となることが近年明らかとなり、社会的にも公衆衛生学的にも歯周病対策の重要性は高まっている。さらに、糖化終末化合物 Advanced glycation end products (AGEs)の蓄積が歯周病の増悪因子となることが明らかになった。そこで、著者は、コラーゲンに特異的に蓄積する AGEs構造体の CMAに着目し、CMA の生成を抑制するとともに歯周病原菌Pgの増殖抑制する天然素材の探索を行い、歯周病と歯周病関連の全身疾患を予防・改善できる有効な食品関連素材の開発を企図した。

Outline of Final Research Achievements

In this study, we searched for natural compounds that inhibit the growth of the periodontal pathogen Porphyromonas gingivalis (Pg) using materials that can be consumed daily and found petroselinic acid from Foeniculum vulgare, mahanimbine from curry leaves, and Epigallocatechin-3-O-gallate from matcha tea as active compounds. We also focused on CMA (Nε-(carboxymethyl) arginine), an advanced glycation end-product that accumulates explicitly in collagen, which is abundant in the oral environment and searched for natural compounds that inhibit the formation of CMA. Xanthohumol D from hops and (-)-catechin from Ampelopsis glandulosa var. heterophylla were found as active compounds.

Academic Significance and Societal Importance of the Research Achievements

歯周病は口腔のみならず、糖尿病や動脈硬化症などの全身疾患の誘因となることが近年明らかとなり、社会的にも公衆衛生学的にも歯周病対策の重要性は高まっている。とりわけ、薬剤耐性菌の問題が深刻化している現在、抗菌薬に頼らない方法、たとえば抗菌活性を有する食品を応用した歯周病制御法の確立が求められている。本研究により、食品由来エキスと化合物の強力なPgの増殖抑制活性と作用機序の詳細を明らかすることができた。また、抗糖化(CMA生成抑制)化合物の活性に必須のコア構造を新たに示すこともできた。これらの知見より、歯周病と歯周病関連の全身疾患を予防・改善できる食品素材候補を見つける手立てが明らかとなった。

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 2023 2022 2021 2020

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] The unique activity of saponin: Induction of cytotoxicity in HTLV-1 infected cells2023

    • Author(s)
      Shida Wataru、Tahara Yurika、Morikawa Saki、Monde Kazuaki、Koga Ryoko、Ohsugi Takeo、Otsuka Masami、Ikemoto Atsushi、Tateishi Hiroshi、Ikeda Tsuyoshi、Fujita Mikako
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 91 Pages: 117408-117408

    • DOI

      10.1016/j.bmc.2023.117408

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and Quantification of 2-O-Caffeoyl-hydroxycitric Acid, an Active Component in Hot Water Extracts of Coriander (Coriandrum sativum L.), Which Inhibits Degranulation of RBL-2H3 Cells2023

    • Author(s)
      Ikeda Tsuyoshi、Sugahara Takuya、Kanamitsu Honoka、Nakashima Keisuke、Onda Hiroyuki、Yoshino Nanami、Nishi Kosuke、Ishida Momoko
    • Journal Title

      Natural Product Communications

      Volume: 18 Issue: 7

    • DOI

      10.1177/1934578x231183603

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Onionin A inhibits small-cell lung cancer proliferation through suppressing STAT3 activation induced by macrophages-derived IL-6 and cell?cell interaction with tumor-associated macrophage2023

    • Author(s)
      Mito Remi、Iriki Toyohisa、Fujiwara Yukio、Pan Cheng、Ikeda Tsuyoshi、Nohara Toshihiro、Suzuki Makoto、Sakagami Takuro、Komohara Yoshihiro
    • Journal Title

      Human Cell

      Volume: 36 Issue: 3 Pages: 1068-1080

    • DOI

      10.1007/s13577-023-00895-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Garlicnin B1, an Active Cyclic Sulfide from Garlic, Exhibits Potent Anti-Inflammatory and Anti-Tumor Activities2023

    • Author(s)
      Gao Shanghui、Yang Kai、Nohara Toshihiro、Ikeda Tsuyoshi、Zhou Jian-Rong、Yokomizo Kazumi、Fang Jun
    • Journal Title

      Antioxidants

      Volume: 12 Issue: 4 Pages: 869-869

    • DOI

      10.3390/antiox12040869

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] LC-MS/MS metabolomics profiling of Glechoma hederacea L. methanolic extract; in vitro antimicrobial and in vivo with in silico wound healing studies on Staphylococcus aureus infected rat skin wound2023

    • Author(s)
      El-Aasr Mona、Nohara Toshihiro、Ikeda Tsuyushi、Abu-Risha Sally E.、Elekhnawy Engy、Tawfik Haytham O.、Shoeib Nagwa、Attia Ghada
    • Journal Title

      Natural Product Research

      Volume: 37 Issue: 10 Pages: 1730-1734

    • DOI

      10.1080/14786419.2022.2108421

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Dual Inhibitory Activity of Petroselinic Acid Enriched in Fennel Against Porphyromonas gingivalis2022

    • Author(s)
      Yoshino Nanami、Ikeda Tsuyoshi、Nakao Ryoma
    • Journal Title

      Frontiers in Microbiology

      Volume: 13 Pages: 816047-816047

    • DOI

      10.3389/fmicb.2022.816047

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A new steroidal glycoside from the fruits of Solanum myriacanthum2022

    • Author(s)
      Ono Masateru、Shimode Mizuki、Tsutsumi Shuhei、Yasuda Shin、Okawa Masafumi、Kinjo Junei、Miyashita Hiroyuki、Ikeda Tsuyoshi、Yoshimitsu Hitoshi、Nohara Toshihiro
    • Journal Title

      Natural Product Research

      Volume: 36 Issue: 1 Pages: 326-333

    • DOI

      10.1080/14786419.2020.1781117

    • Related Report
      2022 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Supramolecular Assembly of Hybrid Pt(II) Porphyrin/Tomatine Analogues with Different Nanostructures and Cytotoxic Activities2021

    • Author(s)
      Fujitsuka Mayuko、Iohara Daisuke、Oumura Sae、Matsushima Misaki、Sakuragi Mina、Anraku Makoto、Ikeda Tsuyoshi、Hirayama Fumitoshi、Kuroiwa Keita
    • Journal Title

      ACS Omega

      Volume: 6 Issue: 20 Pages: 13284-13292

    • DOI

      10.1021/acsomega.1c01239

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of oral moisturizing gel containing propolis following head and neck radiotherapy: randomized controlled pilot trial2021

    • Author(s)
      Ryoma Nakao, Takao Ueno
    • Journal Title

      BDJ Open

      Volume: 7 Issue: 10 Pages: 12-12

    • DOI

      10.3390/pathogens10101286

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Thiolane-type sulfides from garlic, onion, and Welsh onion2021

    • Author(s)
      Nohara Toshihiro、Fujiwara Yukio、El-Aasr Mona、Ikeda Tsuyoshi、Ono Masateru、Nakano Daisuke、Kinjo Junei
    • Journal Title

      Journal of Natural Medicines

      Volume: 75 Issue: 4 Pages: 741-751

    • DOI

      10.1007/s11418-021-01533-x

    • NAID

      40022680465

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Determination of absolute configuration of the most abundant garlic sylfide, garlicnin B1.2021

    • Author(s)
      T. Nohara、M. El-Aasr、T. Ikeda、S.-H. Gao、K. Yokomizo
    • Journal Title

      Curr. Top. Phytochem.

      Volume: 17

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Antipruritic and anti-herpes virus activities of bisabolol oxide A, the main constituent in the essential oil of German chamomile (Matricaria recutita L.)2021

    • Author(s)
      Ikeda-Ogata I、Yamasak Ki、Yokomizo K、Ikeda T、Seo H
    • Journal Title

      Curr. Top. Phytochem.

      Volume: 17

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Drosera tokaiensis extract containing multiple phenolic compounds inhibits the formation of advanced glycation end-products2020

    • Author(s)
      Tominaga Yuki、Sugawa Hikari、Hirabayashi Keita、Ikeda Tsuyoshi、Hoshi Yoshikazu、Nagai Ryoji
    • Journal Title

      Archives of Biochemistry and Biophysics

      Volume: 693 Pages: 108586-108586

    • DOI

      10.1016/j.abb.2020.108586

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Flavonoid Compounds Contained in Epimedii Herba Inhibit Tumor Progression by Suppressing STAT3 Activation in the Tumor Microenvironment2020

    • Author(s)
      Pan Cheng、Fujiwara Yukio、Horlad Hasita、Shiraishi Daisuke、Iriki Toyohisa、Tsuboki Jyunko、Ikeda Tsuyoshi、Komohara Yoshihiro
    • Journal Title

      Frontiers in Pharmacology

      Volume: 11 Pages: 00262-00262

    • DOI

      10.3389/fphar.2020.00262

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] NATURAL COMPOUNDS IN EUCOMMIA ULMOIDES LEAVES INHIBTS THE CML FORMATION BY INHIBITION OF GLYOXAL PRODUCTION VIA OXIDATION OF REDUSING SUGAR2023

    • Author(s)
      Hikari Sugawa, Tsuyoshi Ikeda, Yuki Tominaga, Nana Katsuta and Ryoji Nagai
    • Organizer
      The 30th FAOBMB & 8th BMB Conference
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mahanimbineは歯周病原細菌の表面にクレーター状の穴を開ける2023

    • Author(s)
      中尾龍馬、池田 剛、明田幸宏
    • Organizer
      第96回 日本生化学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 生薬、民間薬由来の抗糖化成分の探索研究:ノブドウについて2023

    • Author(s)
      中嶋圭介、合澤 慎、桑田直幸、辻本真理乃、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
    • Organizer
      第33回日本メイラード学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ホップに含まれる終末糖化産物(AGEs)生成阻害活性化合物の探索研究(Ⅱ)2023

    • Author(s)
      中嶋圭介、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
    • Organizer
      日本生薬学会第69回年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] フェンネルシード由来ペトロセリン酸による口腔環境改善の可能性2023

    • Author(s)
      吉野七海、小池麻里子、伊藤建吾、恩田浩幸、池田 剛、中尾龍馬
    • Organizer
      第77回日本栄養・食糧学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ホップに含まれる終末糖化産物 (AGEs) 生成阻害活性化合物の探索研究2023

    • Author(s)
      中嶋圭介、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
    • Organizer
      日本薬学会第143年会(札幌)
    • Related Report
      2022 Research-status Report
  • [Presentation] Analysis of antioxidative polyphenols from Virgin moringa leaves2022

    • Author(s)
      Shoko Nishizono, Kae Satake, Toru Yomoda, Nobuhiro Fukuda, Tsuyoshi Ikeda, Toshihiro Matsui
    • Organizer
      第22回国際栄養学会議、 東京国際フォーラム
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] コリアンダー(Coriandrum sativum L.)葉水抽出物の脱顆粒抑制成分の探索研究2022

    • Author(s)
      池田 剛 、中嶋圭介、金光穂乃花、石田萌子、西 甲介、恩田浩幸、吉野七海、菅原卓也
    • Organizer
      日本生薬学会第68回年会(松山)
    • Related Report
      2022 Research-status Report
  • [Presentation] ポルフィロモナス・ジンジバリスに対するフェンネルの二重阻害活性2022

    • Author(s)
      吉野七海、池田 剛 、中尾龍馬
    • Organizer
      第36回 日本香辛料研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] イカリソウに含まれるプレニルフラボノイド類のAGEs生成阻害活性について2022

    • Author(s)
      中嶋圭介、宮下裕幸、吉満 斉、藤原章雄、永井竜児、池田 剛
    • Organizer
      第32回日本メイラード学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Dual inhibitory effects of fennel seeds against Porphyromonas gingivalis2021

    • Author(s)
      Nanami Yoshino、Tsuyoshi Ikeda、Ryoma Nakao
    • Organizer
      World Microbe Forum
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Porphyromonas gingivalisに対するmahanimbineの阻害活性2021

    • Author(s)
      中尾龍馬、池田 剛
    • Organizer
      第44回日本分子生物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] 未病改善に有効なファイトケミカルの探索研究について2021

    • Author(s)
      池田 剛
    • Organizer
      第九回全国薬草シンポジウム
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 医食同源の観点より糖化やコレステロールの蓄積を予防する機能性成分の探索研究2020

    • Author(s)
      池田 剛
    • Organizer
      令和2年度 日本栄養・食糧学会九州・沖縄支部大会(熊本)
    • Related Report
      2020 Research-status Report
    • Invited

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

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