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An applicable study of tricin for prevention and treatment of alphaherpesviral infections diseases

Research Project

Project/Area Number 16K09948
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionHokuriku University

Principal Investigator

Takemoto Masaya  北陸大学, 薬学部, 講師 (60379237)

Project Period (FY) 2016-10-21 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords水痘帯状疱疹ウイルス / 単純ヘルペスウイルス / tricin / acyclovir / 急性網膜壊死 / 網膜ミュラー細胞 / ケモカイン / マトリックスメタロプロテアーゼ / 水筒帯状疱疹ウイルス / Tricin / 再活性化 / 母子感染
Outline of Final Research Achievements

Alphaherpesviruses such as varicella-zoster virus (VZV) and herpes simplex virus (HSV) occasionally cause severe infectious diseases like acute retinal necrosis (ARN) for which acyclovir (ACV) is not enough effective. In the present study, I addressed the applicable possibility that a flavonoid, tricin, exhibiting a potent antiviral activity could be an alternative or supportive drug of ACV. I found human retinal Muller cell line as a in vitro model of pathogenesis of ARN in which production of several inflammatory factors including IL-8 and MMP-13 was increased in response to VZV infection. Furthermore, it was demonstrated that tricin showed stronger antiviral and antiinflammatory effects than ACV in the infected cells. These results suggest that tricin could be a promising candidate of an alternative or supportive drug of ACV in the treatment of ARN.

Academic Significance and Societal Importance of the Research Achievements

本研究により、これまでに不明であったARNの発症機序の一端として、ウイルスに感染した網膜Muller細胞から産生されるケモカインやプロテアーゼの関与の可能性が示唆された。またACVでは同細胞でのウイルス増殖を完全に抑制することはできなかった。このことはACV単剤ではARNの進行を止められないことと符合する。さらに天然のフラボノイドであるtricinが、ACVよりも強い抗ウイルス効果・抗炎症効果を網膜Muller細胞で示すことを明らかにした。このことは、現在のARNの治療成績を改善する新たな治療薬候補となる可能性があり、臨床上大きな意義を持つ成果といえる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2018 2017 2016

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] An in silico-designed flavone derivative, 6-fluoro-4′-hydroxy-3′,5′-dimethoxyflavone, has a greater anti-human cytomegalovirus effect than ganciclovir in infected cells2018

    • Author(s)
      Kazuhiro J. Fujimoto, Daiki Nema, Masayuki Ninomiya, Mamoru Koketsu, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
    • Journal Title

      Antivir. Res.

      Volume: 154 Pages: 10-16

    • DOI

      10.1016/j.antiviral.2018.03.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tricin inhibits CCL5 induction required for the efficient growth of human cytomegalovirus2018

    • Author(s)
      Akimasa Itho, Hidetaka Sadanari, Masaya Takemoto, Keiko Matsubara, Tohru Daikoku, Tsugiya Murayama
    • Journal Title

      Microbiology and Immunology

      Volume: 62 Issue: 5 Pages: 341-347

    • DOI

      10.1111/1348-0421.12590

    • NAID

      40021560453

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The anti-human cytomegalovirus drug tricin inhibits cyclin-dependent kinase 92018

    • Author(s)
      Hidetaka Sadanari, Kazuhiro J. Fujimoto, Yuto Sugihara, Tomoki Ishida, Masaya Takemoto, Tohru Daikoku, Tsugiya Murayama
    • Journal Title

      FEBS Open Bio

      Volume: 8 Issue: 4 Pages: 646-654

    • DOI

      10.1002/2211-5463.12398

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of susceptibility variants of poliovirus grown in the presence of favipiravir2017

    • Author(s)
      Tohru Daikoku, Mineyuki Mizuguchi, Takayuki Obita, Takeshi Yokoyama, Yoshihiro Yoshida, Masaya Takemoto, Kimiyasu Shiraki
    • Journal Title

      Journal of Microbiology, Immunology and Infection

      Volume: 印刷中 Issue: 5 Pages: 30100-7

    • DOI

      10.1016/j.jmii.2017.03.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of human cytomegalovirus replication by tricin is associated with depressed CCL2 expression2017

    • Author(s)
      Yumiko Akai, Hidetaka Sadanari, MasayaTakemoto, Noboru Uchide, Tohru Daikoku, Naofumi Mukaida, Tsugiya Murayama
    • Journal Title

      Antiviral Research

      Volume: 148 Pages: 15-19

    • DOI

      10.1016/j.antiviral.2017.09.018

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Profile of anti-herpetic action of ASP2151 (amenamevir) as a helicase-primase inhibitor.2017

    • Author(s)
      Misako Yajima, Hiroshi Yamada, Masaya Takemoto, Tohru Daikoku, Yoshihiro Yoshida, Tan Long, Tomoko Okuda, Kimiyasu Shiraki.
    • Journal Title

      Antiviral Research

      Volume: 139 Pages: 95-101

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Interaction of immunoglobulin with cytomegalovirus-infected cells.2017

    • Author(s)
      Nobuyasu Aiba, Atsuko Shiraki, Misako Yajima, Yukari Oyama, Yoshihiro Yoshida, Ayumu Ohno, Hiroshi Yamada, Masaya Takemoto, Tohru Daikoku, Kimiyasu Shiraki
    • Journal Title

      Viral Immunology

      Volume: 印刷中 Issue: 7 Pages: 500-507

    • DOI

      10.1089/vim.2016.0151

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Proinflammatory responses to VZV infection in human retinal cell lines.2018

    • Author(s)
      Masaya Takemoto, Chikako Yasumura, Kaede Sawano, Toshimi Satoh, Hidetaka Sadanari, Keiko Matsubara, Tsugiya Murayama, Tohru Daikoku
    • Organizer
      第66回日本ウイルス学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Tricinは単純ヘルペスウイルス1型・2型、ならびに水痘帯状疱疹ウイルスの増殖を抑制する2017

    • Author(s)
      武本眞清、定成秀貴、大黒徹、松原京子、村山次哉
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 抗ヒトサイトメガロウイルス活性のあるtricinによるRNA polymerase II C-terminal domainリン酸化の阻害2017

    • Author(s)
      定成秀貴、杉原雄斗、藤本和宏、武本眞清、大黒徹、村山次哉
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 強力な抗ヒトサイトメガロウイルス活性を有する新規化合物の創薬2017

    • Author(s)
      村山次哉、根間大貴、藤本和宏、纐纈守、二ノ宮真之、定成秀貴、武本眞清、大黒徹
    • Organizer
      第65回日本ウイルス学会
    • Related Report
      2017 Research-status Report
  • [Presentation] CCL2/CCR2-dependent replication of human cytomegalovirus is inhibited by anti-inflammatory compound tricin2017

    • Author(s)
      Tsugiya Murayama, Daiki Nema, Hidetaka Sadanari, Masaya Takemoto, Tohru Daikoku, Naofumi Mukaida
    • Organizer
      5th Annual Meeting of the International Cytokine & Interferon Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Tricinは単純ヘルペスウイルスおよび 水痘帯状疱疹ウイルスの増殖を抑制する2016

    • Author(s)
      武本眞清
    • Organizer
      日本薬学会北陸支部第128回例会
    • Place of Presentation
      北陸大学
    • Related Report
      2016 Research-status Report

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Published: 2016-10-24   Modified: 2020-03-30  

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