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Elucidation of the bladder clock function using flavonoids and its application for timed therapy in nocturia patients

Research Project

Project/Area Number 18K09154
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56030:Urology-related
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kyoto Medical Center

Principal Investigator

ITO Haruki  独立行政法人国立病院機構(京都医療センター臨床研究センター), 臨床研究企画運営部, 研究員 (10817448)

Co-Investigator(Kenkyū-buntansha) 後藤 崇之  京都大学, 医学研究科, 講師 (90806605)
根来 宏光  筑波大学, 医学医療系, 准教授 (80708595)
奥野 博  独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究室長 (90263079)
坂根 直樹  独立行政法人国立病院機構(京都医療センター臨床研究センター), 臨床研究企画運営部, 研究室長 (40335443)
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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords夜間頻尿 / 時計遺伝子 / ノビレチン / フラボノイド系化合物 / 概日リズム
Outline of Final Research Achievements

Nocturia can be considered a circadian rhythm disorder. Nobiletin and tangeretin (NoT) are flavonoids derived from the peel of Citrus depressa, and they have been found to modulate circadian rhythms. Nocturia patients with an average age of 73.5 years received NoT50mg (30 mg of nobiletin + 15 mg of tangeretin) once daily for 6 weeks. NoT showed little change in noctrunal bladder capacity but resulted in decreased nighttime frequency (-0.5 voids) with a tendency toward reduced nocturnal polyuria index (nocturnal urine volume). No adverse events directly related to NoT were observed. Our study provides potential evidence of a novel and safe therapeutic option for nocturia.

Academic Significance and Societal Importance of the Research Achievements

夜間頻尿は下部尿路症状の中で最も困窮度が高い症状と言われその病因が多因子であり治療が臨床的に困難なことが多い。また実臨床において高齢者が多いため、安全かつ夜間頻尿を改善させるノビレチン・タンゲレチン混合物が期待される。
基礎研究からは、ノビレチンは尿路上皮細胞株の時計遺伝子発現を増強させコネキシン43のタンパク発現に影響を与えた。排尿機能に影響を与える可能性が示唆された。

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

    (6 results)

All 2023 2022 2019 2018

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

  • [Journal Article] Effectiveness and Safety of a Mixture of Nobiletin and Tangeretin in Nocturia Patients: A Randomized, Placebo-Controlled, Double-Blind, Crossover Study2023

    • Author(s)
      Ito Haruki、Negoro Hiromitsu、Kono Jin、Hayata Naoki、Miura Takayoshi、Manabe Yumi、Miyazaki Yu、Mishina Mutsuki、Woo Je Tae、Sakane Naoki、Okuno Hiroshi
    • Journal Title

      Journal of Clinical Medicine

      Volume: 12 Issue: 8 Pages: 2757-2757

    • DOI

      10.3390/jcm12082757

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 夜間頻尿患者に対するノビレチン・タンゲレチン混合物の効果と安全性に関する研究(NoT-nocturia study):ランダム化プラセボ対照2重盲検化クロスオーバー比較試験2022

    • Author(s)
      伊東晴喜、根来宏光、河野仁、渡邊岳之、早田直生、三浦高慶、真鍋由美、宮崎有、三品睦輝、禹済泰、奥野博
    • Organizer
      第29回日本排尿機能学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Efficacy and safety of a mixture of Nobiletin and Tangeretin in patients with nocturia (NoT-N octuria study): A randomized, placebo-controlled, double-blind, crossover study2022

    • Author(s)
      Ito H, Negoro H, Kono J, Igarashi A, Hayata N, Miura T, Manabe Y, Miyazaki Y, Mishina M, Woo J, Okuno H
    • Organizer
      52th International Continence Society
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 夜間頻尿におけるノビレチンの効果と安全性2022

    • Author(s)
      伊東晴喜
    • Organizer
      ノビレチン研究会第6回学術研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] フラボノイド系化合物ノビレチンの膀胱時計遺伝子発現に対する影響2019

    • Author(s)
      河野仁、根来宏光、上田政克、千菊敦士、小川修
    • Organizer
      第26回時間生物学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 実地医家のための夜間頻尿の治療2018

    • Author(s)
      伊東 晴喜
    • Organizer
      第23回内科-泌尿器科 病診連携の会 藤ノ森カンファレンス
    • Related Report
      2018 Research-status Report

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

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