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Mode-of-action analysis of Kampo formulae and prediction of their new indications for a wide range of diseases

Research Project

Project/Area Number 16H05276
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General internal medicine(including psychosomatic medicine)
Research InstitutionUniversity of Toyama

Principal Investigator

Kadowaki Makoto  富山大学, 和漢医薬学総合研究所, 教授 (20305709)

Co-Investigator(Kenkyū-buntansha) 柴原 直利  富山大学, 和漢医薬学総合研究所, 教授 (10272907)
東田 千尋  富山大学, 和漢医薬学総合研究所, 教授 (10272931)
林 周作  富山大学, 和漢医薬学総合研究所, 助教 (10548217)
山西 芳裕  九州大学, 生体防御医学研究所, 准教授 (60437267)
山本 武  富山大学, 和漢医薬学総合研究所, 助教 (70316181)
梅嵜 雅人  富山大学, 和漢医薬学総合研究所, 准教授 (80534370)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords漢方薬 / ドラッグ・リポジショニング / 複雑系 / 医薬ビッグデータ / 機械学習 / in silico結合シミュレーション / インシリコ / 機械学習手法 / 結合シミュレーション / 標的タンパク質探索 / 実験薬理学的検証 / 和漢医薬学 / リポジショニング / 標的タンパク質 / 東洋医学
Outline of Final Research Achievements

Natural medicines are useful for treatment of multifactorial and chronic diseases. Here, we present KampoDB, a novel platform for the analysis of natural medicines, which provides various useful scientific resources on Japanese traditional formulas Kampo medicines, constituent herbal drugs, constituent compounds, and target proteins of these constituent compounds. Potential target proteins of these constituent compounds were predicted by docking simulations and machine learning methods based on large-scale omics data (e.g., genome, proteome, metabolome, interactome). The current version of KampoDB contains 42 Kampo medicines, 54 crude drugs, 1230 constituent compounds, 460 known target proteins, and 1369 potential target proteins, and has functional annotations for biological pathways and molecular functions. KampoDB is useful for mode-of-action analysis of natural medicines and prediction of new indications for a wide range of diseases.

Academic Significance and Societal Importance of the Research Achievements

漢方薬治療は17世紀頃に体系化され現在へと継承されているが、現代特有の疾患に対して、漢方薬を科学的・論理的・合理的に活用するための科学的取り組みは、体系的にはほとんど行われていない。なぜ漢方薬が効くのかを解明するためには、これまでにない研究方法論を確立することが必要である。
本研究では、漢方医薬ビッグデータを有効活用できるアルゴリズム/データベースKampoDBを開発することによって、複雑系薬剤である漢方薬が複雑系である生体でどのように作用するかを解明するための新たな複雑系解析方法を提示すると共に、漢方薬を用いた新しい疾病治療戦略の創生という新たな可能性を示した。

Report

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

    (37 results)

All 2019 2018 2017 2016

All Journal Article (22 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 22 results,  Open Access: 16 results,  Acknowledgement Compliant: 4 results) Presentation (15 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results)

  • [Journal Article] The Use of Large-Scale Chemically-Induced Transcriptome Data Acquired from LINCS to Study Small Molecules.2019

    • Author(s)
      Iwata M, Yamanishi Y.
    • Journal Title

      Methods Mol Biol.

      Volume: 1888 Pages: 189-203

    • DOI

      10.1007/978-1-4939-8891-4_11

    • ISBN
      9781493988907, 9781493988914
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Distance-Based Boolean Applicability Domain for Classification of High Throughput Screening Data.2019

    • Author(s)
      Berenger F, Yamanishi Y.
    • Journal Title

      J Chem Inf Model.

      Volume: 59 Issue: 1 Pages: 463-476

    • DOI

      10.1021/acs.jcim.8b00499

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chemoinformatics and structural bioinformatics in OCaml.2019

    • Author(s)
      Berenger F, Zhang KYJ, Yamanishi Y.
    • Journal Title

      J Cheminform.

      Volume: 11 Issue: 1 Pages: 10-10

    • DOI

      10.1186/s13321-019-0332-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acteoside Improves Muscle Atrophy and Motor Function by Inducing New Myokine Secretion in Chronic Spinal Cord Injury.2019

    • Author(s)
      Kodani A, Kikuchi T, Tohda C.
    • Journal Title

      J Neurotrauma.

      Volume: 35 Issue: 12 Pages: 1-14

    • DOI

      10.1089/neu.2018.6000

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sparse Modeling to Analyze Drug-Target Interaction Networks.2018

    • Author(s)
      Yamanishi Y.
    • Journal Title

      Methods Mol Biol.

      Volume: 1807 Pages: 181-193

    • DOI

      10.1007/978-1-4939-8561-6_13

    • ISBN
      9781493985609, 9781493985616
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KampoDB, database of predicted targets and functional annotations of natural medicines.2018

    • Author(s)
      Sawada R, Iwata M, Umezaki M, Usui Y, Kobayashi T, Kubono T, Hayashi S, Kadowaki M, Yamanishi Y.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 11216-11216

    • DOI

      10.1038/s41598-018-29516-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Linear and Kernel Model Construction Methods for Predicting Drug-Target Interactions in a Chemogenomic Framework.2018

    • Author(s)
      Yamanishi Y.
    • Journal Title

      Methods Mol Biol.

      Volume: 1825 Pages: 355-368

    • DOI

      10.1007/978-1-4939-8639-2_12

    • ISBN
      9781493986385, 9781493986392
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathway-Based Drug Repositioning for Cancers: Computational Prediction and Experimental Validation.2018

    • Author(s)
      Iwata, M., Hirose, L., Kohara, H., Liao, J., Sawada, R., Akiyoshi, S., Tani, K., Yamanishi, Y.
    • Journal Title

      J Med Chem.

      Volume: 61 Issue: 21 Pages: 9583-9595

    • DOI

      10.1021/acs.jmedchem.8b01044

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matrine Directly Activates Extracellular Heat Shock Protein 90, Resulting in Axonal Growth and Functional Recovery in Spinal Cord Injured-Mice.2018

    • Author(s)
      Tanabe N, Kuboyama T, Tohda C.
    • Journal Title

      Front Pharmacol.

      Volume: 9 Pages: 446-446

    • DOI

      10.3389/fphar.2018.00446

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diosgenin restores Aβ-induced axonal degeneration by reducing the expression of heat shock cognate 70 (HSC70).2018

    • Author(s)
      Yang X, Tohda C.
    • Journal Title

      Sci Rep.

      Volume: 8 Issue: 1 Pages: 11707-11707

    • DOI

      10.1038/s41598-018-30102-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular Neuroleukin Enhances Neuroleukin Secretion From Astrocytes and Promotes Axonal Growth in vitro and in vivo.2018

    • Author(s)
      Tanie Y, Tanabe N, Kuboyama T, Tohda C.
    • Journal Title

      Front Pharmacol.

      Volume: 9 Pages: 1228-1228

    • DOI

      10.3389/fphar.2018.01228

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heat Shock Cognate 70 Inhibitor, VER-155008, Reduces Memory Deficits and Axonal Degeneration in a Mouse Model of Alzheimer’s Disease2018

    • Author(s)
      Yang X., Tohda C.
    • Journal Title

      Front Pharmacol.

      Volume: 9 Pages: 48-48

    • DOI

      10.3389/fphar.2018.00048

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PI3K p85alpha Subunit-deficient Macrophages Protect Mice from Acute Colitis due to the Enhancement of IL-10 Production.2017

    • Author(s)
      Hayashi S., Hamada T., Zinsou D. G. A., Oshiro M., Itoi K., Yamamoto T., Kadowaki M.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 6187-6187

    • DOI

      10.1038/s41598-017-06464-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Polygalae Radix extract prevents axonal degeneration and memory deficits in a transgenic mouse model of Alzheimer’s disease2017

    • Author(s)
      Kuboyama T., Hirotsu K., Arai T., Yamasaki H., Tohda C.
    • Journal Title

      Front Pharmacol.

      Volume: 8 Pages: 805-805

    • DOI

      10.3389/fphar.2017.00805

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diosgenin-Rich Yam Extract Enhances Cognitive Function: A Placebo-Controlled, Randomized, Double-Blind, Crossover Study of Healthy Adults.2017

    • Author(s)
      Tohda C., Yang X., Matsui M., Inada Y., Kadomoto E., Nakada S., Watari H., Shibahara N.
    • Journal Title

      Nutrients

      Volume: 9 Issue: 10 Pages: 1160-1160

    • DOI

      10.3390/nu9101160

    • NAID

      120006375104

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular Cytosolic Aspartate Aminotransferase Promotes Axonal Growth and Object Recognition Memory.2017

    • Author(s)
      Kobayashi R., Tohda C.
    • Journal Title

      Neurochem Res.

      Volume: 42 Issue: 12 Pages: 3465-3473

    • DOI

      10.1007/s11064-017-2394-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A systematic strategy for discovering a therapeutic drug for Alzheimer’s disease and its target molecule2017

    • Author(s)
      Yang Z., Kuboyama T., Tohda C.
    • Journal Title

      Frontiers in Pharmacology

      Volume: 8 Pages: 340-340

    • DOI

      10.3389/fphar.2017.00340

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-Inducer Kakkonto in a Murine Food Allergy Model.2017

    • Author(s)
      Nagata Y, Yamamoto T, Hayashi M, Hayashi S, Kadowaki M.
    • Journal Title

      PLoS One.

      Volume: 12 Issue: 1 Pages: e0170577-e0170577

    • DOI

      10.1371/journal.pone.0170577

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Induction of regulatory T cells as a novel mechanism underlying the therapeutic action of kakkonto, a
traditional Japanese herbal medicine, in a murine food allergy model2016

    • Author(s)
      Yamamoto T, Fujiwara K, Tsubota Y, Kageyama-Yahara N, Hayashi S, Kadowaki M
    • Journal Title

      International Archives of Allergy and Immunology

      Volume: 169 Issue: 3 Pages: 146-156

    • DOI

      10.1159/000445433

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The extract of roots of Sophora flavescens enhances the recovery of motor function by axonal growth in mice with a spinal cord injury.2016

    • Author(s)
      Tanabe N, Kuboyama T, Kazuma K, Konno K, Tohda C.
    • Journal Title

      Frontiers in Pharmacology

      Volume: 6:326 Pages: 1-10

    • DOI

      10.3389/fphar.2015.00326

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Extracellular vimentin is a novel axonal growth facilitator for functional recovery in spinal cordinjured mice.2016

    • Author(s)
      Shigyo M, Tohda C.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 28293-28293

    • DOI

      10.1038/srep28293

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] New Age Therapy for Alzheimer’s Disease by Neuronal Network Reconstruction2016

    • Author(s)
      Tohda C.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 10 Pages: 1569-1575

    • DOI

      10.1248/bpb.b16-00438

    • NAID

      130005598483

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Therapeutic effects of inhibitors of the migration of plasmacytoid dendritic cells, but not conventional dendritic cells in a murine colitis model.2018

    • Author(s)
      Zhang Y., Yamamoto T., Kadowaki M.
    • Organizer
      Digestive Disease Week
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Berberine Chloride, an Enhancer of IL-10 Production in Macrophages, Suppresses the Development of an Experimental Colitis in Mice.2018

    • Author(s)
      Hayashi S., Wakabayashi N., Kadowaki M.
    • Organizer
      Digestive Disease Week
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Enhancer of IL-10 production in intestinal macrophages ameliorates an experimental colitis in mice.2018

    • Author(s)
      Hayashi S., Wakabayashi N., Ogawa Y., Hertati A., Kadowaki M.
    • Organizer
      10th International Symposium on Cell/Tissue Injury and Cytoprotection/Organoprotection.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 未病研究の最前線 経験知の「未病」を数理科学を用いて科学知へと導く2017

    • Author(s)
      門脇 真
    • Organizer
      日本臨床薬理学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] インシリコスクリーニングを応用した炎症性腸疾患に対する新規治療薬の探索研究.2017

    • Author(s)
      窪野孝貴, 林 周作, 福西快文, 門脇 真
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Improvement of Therapeutic Efficacy of Oral Immunotherapy in Combination with Regulatory T Cell-inducer Kakkonto in a Murine Food Allergy Model.2017

    • Author(s)
      Kadowaki M., Nagata Y., Hayashi M., Hayashi S., Yamamoto T
    • Organizer
      East-West Integrative Medicine for Immunology & Wellness
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Search for an Enhancer of IL-10 Production in the Intestinal Macrophages for New Therapy against Inflammatory Bowel Disease.2017

    • Author(s)
      Wakabayashi N., Hayashi S., Kadowaki M.
    • Organizer
      Annual Meeting of the International Cytokine & Interferon Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intestinal Regulatory T Cells Induced by Kakkonto, a Traditional Japanese Herbal Medicine, Improve Therapeutic Efficacy of Oral Immunotherapy in Food Allergy Model Mice.2017

    • Author(s)
      Yamamoto T., Nagata Y., Hayashi M., Kadowaki M
    • Organizer
      International Congress of Mucosal Immunology
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 五苓散の基礎と臨床~ 脳外科領域での有用性について2017

    • Author(s)
      柴原直利
    • Organizer
      第34回和漢医薬学会学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] アルツハイマー病の記憶障害を改善する帰脾湯・加味帰脾湯2017

    • Author(s)
      東田千尋
    • Organizer
      第34回和漢医薬学会学術大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] KampoDB: An integrated platform for mode-of-action analysis and repositioning of natural medicines2017

    • Author(s)
      Sawada, R., Iwata, M., Umezaki, M., Usui, Y., Kubono, T., Kadowaki, M., and Yamanishi, Y.
    • Organizer
      情報計算化学生物学会2017年大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Compuational analysis of the mode-of-action and pharmacological effects of Japanese Kampo medicines2017

    • Author(s)
      Sawada, R., Iwata, M., Umezaki, M., Usui, Y., Kubono, T., Kadowaki, M., and Yamanishi, Y.
    • Organizer
      The Sixteenth Asia Pacific Bioinformatics Conference (APBC2018)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Generation of Technologies of Big Data Analysis to Effectively Utilize Kampo Medicines in Medical Practice.2016

    • Author(s)
      Kadowaki M.
    • Organizer
      6th International Symposium in Phytochemicals-Bioactivities and Diseases Prevention of Phytochemicals and Natural Products for Health
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] インシリコスクリーニングを用いた炎症性腸疾患に対する新規治療薬の探索.2016

    • Author(s)
      窪野孝貴, 林 周作, 梅嵜雅人, 門脇 真
    • Organizer
      日本薬学会 北陸支部 第128回例会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 漢方薬成分のインシリコ標的タンパク質探索による漢方薬リポジショニング2016

    • Author(s)
      門脇 真
    • Organizer
      フォーラム富山「創薬」第43回研究会「情報科学・計算科学・数理科学から創薬への新展開~ウェット研究とドライ研究のコラボレーション~」
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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