Five hTRPA1 Agonists Found in Indigenous Korean Mint, Agastache rugosa

• Published in: PloS one 2015-05, Vol.10 (5), p.e0127060-e0127060
• Main Authors: Moon, Hana, Kim, Min Jung, Son, Hee Jin, Kweon, Hae-Jin, Kim, Jung Tae, Kim, Yiseul, Shim, Jaewon, Suh, Byung-Chang, Rhyu, Mee-Ra
• Format: Article
• Language: English
• Subjects: Acetanilides - pharmacology; Agastache; Agastache - chemistry; Agastache rugosa; Allyl isothiocyanate; Anisoles - pharmacology; Benzaldehydes - pharmacology; Brain research; Calcium; Calcium Channels; Calcium compounds; Capsaicin receptors; Carveol; Caryophyllene; Cell culture; Cell Line; Eugenol; Eugenol - analogs & derivatives; Eugenol - pharmacology; Food; Gastric emptying; Health aspects; HEK293 Cells; Humans; Inflammation; Isothiocyanate; Leaves; Methyl eugenol; Monoterpenes - pharmacology; Nerve Tissue Proteins - agonists; Nerve Tissue Proteins - antagonists & inhibitors; Physiological aspects; Phytochemicals; Plant Extracts - pharmacology; Plant Leaves - chemistry; Plant Stems - chemistry; Purines - pharmacology; Rosmarinic acid; Ruthenium; Ruthenium red; Ruthenium Red - pharmacology; Sesquiterpenes - pharmacology; Signaling; Stem cells; Syringate; Transient Receptor Potential Channels - agonists; Transient Receptor Potential Channels - antagonists & inhibitors; Transient receptor potential proteins; TRPA1 Cation Channel; TRPV Cation Channels - agonists
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0127060

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.