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Building a database of TRPA1 agonists derived from traditional Chinese medicine and elucidation of its pharmacological mechanism

Research Project

Project/Area Number 15K21538
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Natural medicines
Pain science
Research InstitutionHyogo University of Health Sciences

Principal Investigator

Wang Shenglan  兵庫医療大学, 薬学部, 助教 (50714359)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsTRPA1 / 漢方薬 / 疼痛
Outline of Final Research Achievements

Using flexstation calcium assay, we screened 27 natural compounds derived from traditional Chinese medicines. Four compounds were identified to activate TRPA1 channel with the higher EC50 values and lower responses. The agonistic effects of these compounds on TRPA1 could be inhibited by HC030031, a selective TRPA1 antagonist, in TRPA1 expressing human X cells and dorsal root ganglion (DRG) neurons. Further studies showed that these compounds induced the desensitization of TRPA1 channel and the analgesic effects on rat pain models. In addition, we identified two compounds (evodiamine and rutaecarpine) which activated TRPV1 channel. Evodiamine partially activated TRPV1 and inhibited TRPV1 activation through competitive partial antagonism and channel desensitization.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2016 2015

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

  • [Journal Article] Partial Activation and Inhibition of TRPV1 Channels by Evodiamine and Rutaecarpine, Two Major Components of the Fruits of Evodia rutaecarpa.2016

    • Author(s)
      Wang S, Yamamoto S, Kogure Y, Zhang W, Noguchi K, Dai Y
    • Journal Title

      J Nat Prod.

      Volume: 79 Issue: 5 Pages: 1225-1230

    • DOI

      10.1021/acs.jnatprod.5b00599

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels.2016

    • Author(s)
      Iwaoka E, Wang S, Matsuyoshi N, Kogure Y, Aoki S, Yamamoto S, Noguchi K, Dai Y.
    • Journal Title

      J Nat Med

      Volume: 70 Issue: 1 Pages: 1-7

    • DOI

      10.1007/s11418-015-0929-1

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Partial activation and inhibition of TRPV1 channels by evodiamine and rutaecarpine, two major components of evodiae fructus2016

    • Author(s)
      Shenglan Wang, Satoshi Yamamoto, Yoko Kogure, Koichi Noguchi, Yi Dai
    • Organizer
      The 18th International Congress of Oriental Medicine 2016
    • Place of Presentation
      Okinawa Convention Center, Ginowan, Okinawa, Japan
    • Year and Date
      2016-04-16
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エボジアミンはTRPV1チャネルのパーシャルアゴニストである2015

    • Author(s)
      王勝蘭、山本悟史、野口光一、戴毅
    • Organizer
      第37回日本疼痛学会
    • Place of Presentation
      市民会館崇城大学ホール(熊本市民会館)(熊本県熊本市)
    • Year and Date
      2015-07-04
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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