Strategy for allergic diseases treatment based on the function of ayurvedic medicines

• Project/Area Number: 26305004
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 海外学術
• Research Field: Natural medicines
• Research Institution: The University of Tokushima
• Principal Investigator: FUKUI Hiroyuki 徳島大学, 大学院医歯薬学研究部, 特任教授 (90112052)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 花粉症 / アレルギー性鼻炎 / アレルギー疾患 / ヒスタミン / 天然物医薬 / 疾患感受性遺伝子 / 細胞内シグナル / PKCδ / アレルギー / 細胞内シグナル分子 / 積極的併用療法 / 分子標的薬

Outline of Final Research Achievements

A novel benzofuran compound 4-methoxybenzofuran-5-carboxamide (HMBC) was identified as an active ingredient from anti-allergic ayurvedic medicine Tephresia purpurea. MBCA suppressed H1 R gene expression through suppression of PKCd activation. In addition, MBCA isomer showed stronger H1R gene expression inhibitory activity than MBCA. In allergy model rats, it was found that MBCA ameliorates nasal symptoms through suppressing expression of H1R gene and Th2 cytokine gene such as IL-4, IL-5 of nasal mucosa. Furthermore, since MBCA suppresses IL-33 gene expression, it is suggested that not only acute symptoms of allergic rhinitis but also chronic symptoms may be improved by MBCA.

Research Products

• [Journal Article] 抗アレルギー天然物医薬、苦参の有効成分、(-)マーキアインの分子薬理機構 (2016)
  • Author(s): 福井 裕行、水口 博之、柏田 良樹、根本 尚夫、北村 嘉章、武田 憲昭
  • Journal Title: 日本薬理学雑誌 Volume: 147 Pages: 148-151
  • NAID: 130005131662
  • Open Access
• [Journal Article] The isolation and synthesis of a novel benzofuran compound from Tephrosia purpurea, and the synthesis of several related derivatives, which suppress histamine H1 receptor gene expression. (2015)
  • Author(s): Shill MC, Das AK, Itou T, Karmakar S, Mukherjee PK, Mizuguchi H, Kashiwada Y, Fukui H, Nemoto H.
  • Journal Title: Bioorg Med Chem Volume: 23 Pages: 6869-6874
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A novel benzofuran, 4-methoxybenzofuran-5-carboxamide, from Tephrosia purpurea suppressed histamine H1 receptor gene expression through a protein kinase C-δ-dependent signaling pathway. (2015)
  • Author(s): hill MC, Mizuguchi H, Karmakar S, Kadota T, Mukherjee PK, Kitamura T, Kashiwada Y, Nemoto H, Takeda N, Fukui H.
  • Journal Title: Int Immunopharmacol Volume: 30 Pages: 18-26
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Histamine h1 receptor gene as a sensitive gene of nasal hypersensitivity and clinical significance of antihistamines (2016)
  • Author(s): H. Fukui
  • Organizer: 45th Annual Meeting of the European Histamine Research Society
  • Place of Presentation: Florence, Italy
  • Year and Date: 2016-05-11
  • Int'l Joint Research / Invited
• [Presentation] 抗アレルギー天然物医薬有効成分の分子薬理機構（Molecular mechanism of active substances from anti-allergic natural medicines） (2015)
  • Author(s): 福井裕行、水口博之、柏田良樹、根本尚夫、武田憲昭
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場、愛知県・名古屋市
  • Year and Date: 2015-03-18 – 2015-03-20
  • Invited
• [Presentation] Improvement of symptoms by anti-allergic natural medicines through suppression of histamine H1 receptor gene expression (2015)
  • Author(s): H. Fukui
  • Organizer: 2nd International Congress of Society for Ethnopharmacology
  • Place of Presentation: Nagpur, India
  • Year and Date: 2015-02-20 – 2015-02-22
  • Invited
• [Presentation] Molecular mechanism of action of quercetin: Inhibition of PKCδ activation to suppress transcriptional up-regulation of histamine H1 receptor gene expression (2015)
  • Author(s): T. Nakano, H. Mizuguchi, M. Hattori, N. Takeda, H. Fukui
  • Organizer: 2nd International Congress of Society for Ethnopharmacology
  • Place of Presentation: Nagpur, India
  • Year and Date: 2015-02-20 – 2015-02-22
• [Presentation] Isolation of novel anti-allergic compound from Tephrosia purpurea in an activity guided manner and chemical synthesis of the compound (2014)
  • Author(s): M.C. Shill, H. Mizuguchi, H. Fukui
  • Organizer: 第126回日本薬理学会近畿部会
  • Place of Presentation: 和歌山県JAビル、和歌山県・和歌山市
  • Year and Date: 2014-10-24
• [Presentation] Isolation of novel anti-allergic compound from Tephrosia purpurea and chemical synthesis of the compound and its relevant structural compounds (2014)
  • Author(s): M.C. Shill, H. Mizuguchi, H. Fukui
  • Organizer: 第18回日本ヒスタミン学会
  • Place of Presentation: 都ホテルニューアルカイック、兵庫県・尼崎市
  • Year and Date: 2014-10-10 – 2014-10-11
• [Presentation] 抗ヒスタミン薬の抗アレルギー作用発現機構 (2014)
  • Author(s): 福井裕行
  • Organizer: 第21回 四国四大学皮膚科研究会
  • Place of Presentation: ホテルグランドパレス徳島、徳島県・徳島市
  • Year and Date: 2014-06-28
  • Invited
• [Presentation] Improvement of symptoms with correalative suppression of allergic disease-sensitive gene expression (2014)
  • Author(s): H. Fukui, H. Mizuguchi, Y. Kitamura, N. Takeda
  • Organizer: The 43rd European Histamine Research Society Annual Meeting
  • Place of Presentation: Domaine Saint Joseph, Lyon, France
  • Year and Date: 2014-05-06 – 2014-05-09
• [Book] Handbook of Experimental Pharmacology, Histamine Receptors (2016)
  • Author(s): Hiroyuki Fukui, Hiroyuki Mizuguchi, Hisao Nemoto, Yoshiaki Kitamura, Yoshiki Kashiwada and Noriaki Takeda.
  • Total Pages: 9
  • Publisher: Springer Science, NewYork
• [Book] Receptor series, "The Receptors", Histamine Receptors (2016)
  • Author(s): Hiroyuki Fukui, Hiroyuki Mizuguchi, Yoshiaki Kitamura and Noriaki Takeda.
  • Total Pages: 16
  • Publisher: Springer Science, NewYork