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Anti-Toxoplasma and neuroprotective potential of medicinal plant Hypericum

Research Project

Project/Area Number 19K07839
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionOsaka University (2020-2021)
Chiba University (2019)

Principal Investigator

Shinjyo Noriko  大阪大学, 免疫学フロンティア研究センター, 特任研究員(常勤) (60794039)

Co-Investigator(Kenkyū-buntansha) 野呂瀬 一美  千葉大学, 大学院医学研究院, 特任准教授 (30156244)
彦坂 健児  千葉大学, 大学院医学研究院, 准教授 (30456933)
吉田 裕樹  佐賀大学, 医学部, 教授 (40260715)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords寄生虫 / 薬用植物 / 感染症 / トキソプラズマ / 神経系 / 炎症 / 西洋オトギリソウ / ハイパーフォリン / 脳 / グリア細胞 / うつ病 / ヒペリシン / Hypericum / 神経炎症
Outline of Research at the Start

トキソプラズマ症は、日和見感染症である。ストレス誘発性神経炎症による神経・免疫系ネットワークの撹乱が精神神経疾患や生体防御能力低下の要因として注目される中、トキソプラズマ慢性感染に対する免疫応答はストレスによる神経炎症に拍車をかける危険因子と言える。しかし、ストレスによる原虫再活性化と神経症状発症のメカニズムについては未解明な点が多く、予防と治療に向けて複数の標的を考慮した戦略が必要である。
本研究では、抗神経炎症作用や抗病原体効果などの薬効作用の期待される薬用植物オトギリソウとその同属植物に注目し、マウストキソプラズマ慢性感染モデルにおいて、原虫再活性化と神経炎症に対する効果を検証する。

Outline of Final Research Achievements

Toxoplasma gondii is an obligate intracellular protozoan parasite, causing opportunistic infection in approximately one third of the world population. Vertical transmission can cause severe damages to the fetus, while Toxoplasma reactivation in immunocompromised individuals can render debilitating effects. In addition, T. gondii is a neurotropic parasite causing various neuropsychiatric disorders. There is no cure for Toxoplasma chronic infection, thus development of safer and more effective treatment is desired.
Hypericum spp. are plant species well-known for their medicinal properties. These plant species have long been used in folk medicines worldwide. This study investigated anti-Toxoplasma potential of two Hypericum spp., namely H. erectum and H. perforatum, and found that H. perforatum and its unique active constituent Hyperforin are potentially effective against Toxoplasma chronic infection.

Academic Significance and Societal Importance of the Research Achievements

トキソプラズマ慢性感染は日本において10-30%に蔓延するとされる。垂直感染が胎児に重篤な脳障害を来す一方、妊娠中の抗トキソプラズマ薬使用は制限されるため、安全性の高い生薬に期待が寄せられる。また、ストレスの蔓延する現代社会において抗病原体効果・抗神経炎症効果を持つ薬用植物資源の探索は、トキソプラズマ症に限らずサイトメガロウイルスなど、その他の日和見感染症に応用できるものであり、さらに神経炎症が関連する様々な精神神経疾患の治療・予防法の開発にも貢献すると期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (16 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 13 results,  Open Access: 11 results) Presentation (3 results)

  • [Int'l Joint Research] University of Gothenburg(スウェーデン)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Westminster(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Caritas Institute of Higher Education(中国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Sydney(オーストラリア)

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Erdheim-Chester Disease Involving the Central Nervous System with Latent Toxoplasmosis2022

    • Author(s)
      Wadayama Tomoya、Shimizu Mikito、Kimura Ikko、Baba Kousuke、Beck Goichi、Nagano Seiichi、Morita Ryo、Nakagawa Hidenori、Shirano Michinori、Goto Tetsushi、Norose Kazumi、Hikosaka Kenji、Murayama Shigeo、Mochizuki Hideki
    • Journal Title

      Internal Medicine

      Volume: 61 Issue: 17 Pages: 2661-2666

    • DOI

      10.2169/internalmedicine.8564-21

    • NAID

      130008158352

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2022-09-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Editorial: The Relationships Between Infectious Agents and Dementia2022

    • Author(s)
      Too Lay Khoon、Hunt Nicholas H.、Shinjyo Noriko
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 16 Pages: 831374-831374

    • DOI

      10.3389/fncel.2022.831374

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 感染源が不明であったドロレス顎口虫による皮膚爬行症の 1例2022

    • Author(s)
      熊田 大樹、 猪爪 隆史、栗田 遼二、野呂瀬 一美、彦坂 健児、丸山  治彦、松江 弘之
    • Journal Title

      皮膚科の臨床

      Volume: 印刷中

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Infection and Immunometabolism in the Central Nervous System: A Possible Mechanistic Link Between Metabolic Imbalance and Dementia2021

    • Author(s)
      Shinjyo Noriko、Kita Kiyoshi
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 15 Pages: 765217-765217

    • DOI

      10.3389/fncel.2021.765217

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interaction Between the Complement System and Infectious Agents ? A Potential Mechanistic Link to Neurodegeneration and Dementia2021

    • Author(s)
      Shinjyo Noriko、Kagaya Wataru、Pekna Marcela
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 15 Pages: 710390-710390

    • DOI

      10.3389/fncel.2021.710390

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acetate Induces Growth Arrest in Colon Cancer Cells Through Modulation of Mitochondrial Function2021

    • Author(s)
      Sahuri-Arisoylu Meliz、Mould Rhys R.、Shinjyo Noriko、Bligh S. W. Annie、Nunn Alistair V. W.、Guy Geoffrey W.、Thomas Elizabeth Louise、Bell Jimmy D.
    • Journal Title

      Frontiers in Nutrition

      Volume: 8 Pages: 588466-588466

    • DOI

      10.3389/fnut.2021.588466

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Acute exacerbation of pulmonary toxoplasmosis during corticosteroid therapy for immune thrombocytopenia2021

    • Author(s)
      Omori Koji、Imoto Naoto、Norose Kazumi、Maeda Matsuyoshi、Hikosaka Kenji、Kurahashi Shingo
    • Journal Title

      Medicine

      Volume: 100 Issue: 51 Pages: e28430-e28430

    • DOI

      10.1097/md.0000000000028430

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical characteristics and incidence of toxoplasmosis after autologous hematopoietic stem cell transplantation: A retrospective study and literature review2021

    • Author(s)
      Kitahara Mari、Hiroshima Yuki、Norose Kazumi、Hikosaka Kenji、Kazumoto Hiroko、Uematsu Nozomu、Shishido Tsutomu、Kaiume Hiroko、Sato Keijiro、Ueki Toshimitsu、Sumi Masahiko、Watanabe Masahide、Kobayashi Hikaru
    • Journal Title

      Transplant Infectious Disease

      Volume: 23 Issue: 6

    • DOI

      10.1111/tid.13726

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Murine Model of Primary Acquired Ocular Toxoplasmosis: Fluorescein Angiography and Multiplex Immune Mediator Profiles in the Aqueous Humor2021

    • Author(s)
      Li Kexin、Feng Xue、Hikosaka Kenji、Norose Kazumi
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 62 Issue: 3 Pages: 9-9

    • DOI

      10.1167/iovs.62.3.9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 検査キットにより検査値の差が大きかったトキソプラズマIgM抗体持続陽性の 妊婦症例2021

    • Author(s)
      上田菜月,多田克彦,野呂瀬一美,中村 信,熊澤一真
    • Journal Title

      日本周産期・新生児医学会雑誌

      Volume: 57 Pages: 511-515

    • NAID

      130008127727

    • Related Report
      2021 Annual Research Report
  • [Journal Article] トキソプラズマ症 - 領域別症候群シリーズ2021

    • Author(s)
      野呂瀬 一美
    • Journal Title

      呼吸器症候群 (第3版) IV

      Volume: 20 Pages: 205-209

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Hypericum perforatum extract and hyperforin inhibit the growth of neurotropic parasite Toxoplasma gondii and infection-induced inflammatory responses of glial cells in vitro2021

    • Author(s)
      Shinjyo Noriko、Nakayama Hideyuki、Li Li、Ishimaru Kanji、Hikosaka Kenji、Suzuki Noriyuki、Yoshida Hiroki、Norose Kazumi
    • Journal Title

      Journal of Ethnopharmacology

      Volume: 267 Pages: 113525-113525

    • DOI

      10.1016/j.jep.2020.113525

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toxoplasma Infection Induces Sustained Up-Regulation of Complement Factor B and C5a Receptor in the Mouse Brain via Microglial Activation: Implication for the Alternative Complement Pathway Activation and Anaphylatoxin Signaling in Cerebral Toxoplasmosis2021

    • Author(s)
      Shinjyo N, Hikosaka K, Kido Y, Yoshida H, Norose K.
    • Journal Title

      Front Immunol.

      Volume: 11 Pages: 603924-603924

    • DOI

      10.3389/fimmu.2020.603924

    • NAID

      120007000273

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypericum erectum alcoholic extract inhibits Toxoplasma growth and Entamoeba encystation: an exploratory study on the anti-protozoan potential.2020

    • Author(s)
      Shinjyo N, Nakayama H, Ishimaru K, Hikosaka K, Mi-Ichi F, Norose K, Yoshida H.
    • Journal Title

      J Nat Med

      Volume: 74 Issue: 1 Pages: 294-305

    • DOI

      10.1007/s11418-019-01369-6

    • NAID

      40022130373

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Valerian Root in Treating Sleep Problems and Associated Disorders?A Systematic Review and Meta-Analysis2020

    • Author(s)
      Shinjyo Noriko、Waddell Guy、Green Julia
    • Journal Title

      Journal of Evidence-Based Integrative Medicine

      Volume: 25 Pages: 1-31

    • DOI

      10.1177/2515690x20967323

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Berberine for Prevention of Dementia Associated With Diabetes and Its Comorbidities: A Systematic Review2020

    • Author(s)
      Shinjyo N, Parkinson J, Bell J, Katsuno T, Bligh A
    • Journal Title

      J Integr Med

      Volume: 18 Issue: 2 Pages: 125-151

    • DOI

      10.1016/j.joim.2020.01.004

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ナイジェリアの家畜より分離した捻転胃虫の遺伝的多様性解 析2021

    • Author(s)
      カウエ サイモン、バログン エマニュエル、野呂瀬 一美、アデク マイ ケル、彦坂 健児
    • Organizer
      第90回日本寄生虫学会 第32回日本臨床寄生虫学会 合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] トキソプラズマ脳炎の治療 中に中枢性EBV関連リンパ増殖性疾患を発症した一例2021

    • Author(s)
      池亀和博、眞弓あずさ、野呂瀬一美、加藤康幸
    • Organizer
      第95回日本感染症学会学術講演会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Traditional Kampo formula (漢方) Scutellaria-Coptis is protective against Toxoplasma infection via synergistic immunomodulation2019

    • Author(s)
      Noriko Shinjyo, Kenji Hikosaka, Hiroki Yoshida, Kazumi Norose
    • Organizer
      第84回日本インターフェロンサイトカイン学会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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