Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa

PLoS One. 2015 May 15;10(5):e0127060. doi: 10.1371/journal.pone.0127060. eCollection 2015.

Abstract

Transient receptor potential ankyrin1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer) O. Kuntze (A.rugosa), commonly known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem and leaves of A.rugosa (Labiatae) selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and rosmarinic acid) on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2±1.4 μM), our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Agastache / chemistry*
  • Anisoles / pharmacology
  • Benzaldehydes / pharmacology
  • Calcium Channels
  • Cell Line
  • Cyclohexane Monoterpenes
  • Eugenol / analogs & derivatives
  • Eugenol / pharmacology
  • HEK293 Cells
  • Humans
  • Monoterpenes / pharmacology
  • Nerve Tissue Proteins / agonists*
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Plant Extracts / pharmacology
  • Plant Leaves / chemistry
  • Plant Stems / chemistry
  • Polycyclic Sesquiterpenes
  • Purines / pharmacology
  • Ruthenium Red / pharmacology
  • Sesquiterpenes / pharmacology
  • TRPA1 Cation Channel
  • TRPV Cation Channels / agonists
  • Transient Receptor Potential Channels / agonists*
  • Transient Receptor Potential Channels / antagonists & inhibitors

Substances

  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Anisoles
  • Benzaldehydes
  • Calcium Channels
  • Cyclohexane Monoterpenes
  • Monoterpenes
  • Nerve Tissue Proteins
  • Plant Extracts
  • Polycyclic Sesquiterpenes
  • Purines
  • Sesquiterpenes
  • TRPA1 Cation Channel
  • TRPA1 protein, human
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Transient Receptor Potential Channels
  • Ruthenium Red
  • methyleugenol
  • Eugenol
  • carveol
  • estragole
  • 4-anisaldehyde
  • caryophyllene

Grant support

This study was supported by Korea Food Research Institute (E0131201, E0143043494), the National Research Foundation of Korea (NRF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.