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Elucidation of carcinogenesis signaling mechanism by chronic periodontitis and development of drug discovery derived from Kampo medicine

Research Project

Project/Area Number 18K09929
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57080:Social dentistry-related
Research InstitutionOsaka Dental University

Principal Investigator

OH Hourei  大阪歯科大学, 歯学部, 教授 (20213613)

Co-Investigator(Kenkyū-buntansha) 今村 泰弘  松本歯科大学, 歯学部, 講師 (00339136)
Project Period (FY) 2018-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords漢方薬 / 歯周病 / 慢性炎症 / 抗炎症作用 / 発ガン抑制 / がん / 細胞内シグナル伝達 / 歯周医学 / 創薬 / 抗ガン薬
Outline of Final Research Achievements

In oral squamous cell carcinoma cell line CAL27, orento significantly inhibited periodontopathogenic bacterium Porphyromonas gingivalis lipopolysaccharide (LPS) and lipoproteins (PAMP)-stimulated production of interleukin (IL)-6. This finding indicates that orento may suppress the function and activation of factors involved in TLR signaling, thereby suppressing NF-kB-dependent expression of various genes. Orento suppressed IL-1 receptor-associated kinase (IRAK4), IRAK1, and c-Jun N-terminal kinase (JNK) phosphorylation in PAMP-stimulated CAL27 cells. This result indicates that orento is involved in the initiation of TLR signaling by PAMP and suppresses the downstream signaling pathways of myeloid differentiation primary response gene 88 (MyD88) such as mitogen-activated protein kinase (MAPK) and NF-kB cascades. These findings suggest that orento has an inhibitory effect on the production of inflammatory cytokines.

Academic Significance and Societal Importance of the Research Achievements

学術的意義は歯周病関連細菌とがん細胞とのIL-6 の発現を分子生物学的にTLRシグナル伝達経路で解明でき、その経路を漢方薬が遮断したことである。一方、社会的意義としてはまず歯周病は細菌感染による慢性疾患である。つまり慢性疾患はがん発症に関与することから、抗炎症作用のある漢方薬は「未病を防ぐ」発想になり、予防医学に発展すると考えることができる。従って、患者様のがんによる痛みや治療費の負担は軽減する。

Report

(6 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2023 2022 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (7 results) Book (1 results)

  • [Journal Article] Inhibitory mechanism of IL-6 production by orento in oral squamous cell carcinoma cell line CAL27 stimulated by pathogen-associated molecular patterns from periodontopathogenic Porphyromonas gingivalis2023

    • Author(s)
      Imamura Yasuhiro, Makita Yoshimasa, Masuno Kazuya, Oh Hourei
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 1 Pages: 1-9

    • DOI

      10.3390/ijms24010697

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of Orento, a Traditional Japanese Medicine, on IL-6, IL-8 Secretion, Type 1 Collagen Production and Alkaline Phosphatase Secretion in the Human Osteosarcoma Cell Line Saos-22020

    • Author(s)
      Hourei Oh , Kazuya Masuno , Nobutaka Okusa , Yoshimasa Makita , Shin-Ichi Fujiwara , Yasuhiro Imamura
    • Journal Title

      Medicines

      Volume: 7 Issue: 10 Pages: 1-9

    • DOI

      10.3390/medicines7100061

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 柿渋ジェルの口腔病原性微生物に対する抗菌活性2019

    • Author(s)
      王 宝禮, 大草亘孝, 益野一哉
    • Journal Title

      診療と新薬

      Volume: 56 Pages: 694-697

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 歯周病はガンのリスクファクターか2019

    • Author(s)
      王 宝禮
    • Journal Title

      Precision Medicine

      Volume: 2 Pages: 89-92

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 歯周病がガンになるのか2018

    • Author(s)
      王 宝禮
    • Journal Title

      Precision Medicine

      Volume: 1 Pages: 112-115

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 歯科疾患における痛みに対する立効散の有効性2022

    • Author(s)
      王 宝禮、今村泰弘
    • Organizer
      日本耳鼻咽喉科漢方研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 口腔扁平上皮癌細胞に対する黄連湯の癌細胞活性抑制メカニズム解析2022

    • Author(s)
      王 宝禮、今村泰弘
    • Organizer
      日本疼痛漢方研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 川崎病患者の歯科治療後の鎮痛効果を期待する立効散選択の考え方2019

    • Author(s)
      王 宝禮
    • Organizer
      2019年度日本東洋医学会関西支部例会
    • Related Report
      2019 Research-status Report
  • [Presentation] 吉益東洞経験方の処方に基づく排膿散及湯の抗炎症作用機序解明2019

    • Author(s)
      王 宝禮
    • Organizer
      第24回吉益東洞顕彰会
    • Related Report
      2019 Research-status Report
  • [Presentation] 筋骨草のヒト骨芽細胞様骨肉腫細胞における骨形成能及び抗炎症作用の基礎研究2019

    • Author(s)
      王 宝禮
    • Organizer
      第28回硬組織再生生物学会学術大会・総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 歯周病治療と排膿散及湯:骨芽培養細胞に対する作用機序2019

    • Author(s)
      王 宝禮
    • Organizer
      第32回日本疼痛漢方研究会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 歯周炎誘発動物モデルに対する排膿散及湯の影響2019

    • Author(s)
      王 宝禮
    • Organizer
      第62回春季日本歯周病学会学術大会
    • Related Report
      2019 Research-status Report
  • [Book] 薬YEAR BOOK 19/20患者に聞かれても困らない!歯科医師のための「薬」飲み合わせ完全マニュアル.2019

    • Author(s)
      朝波惣一郎, 王 宝禮, 矢郷 香.
    • Total Pages
      189
    • Publisher
      クインテッセンス出版
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2024-01-30  

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