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Essential Oils from <i>Monarda fistulosa</i>: Chemical Composition and Activation of Transient Receptor Potential A1 (TRPA1) Channels
oleh: Monica Ghosh, Igor A. Schepetkin, Gulmira Özek, Temel Özek, Andrei I. Khlebnikov, Derek S. Damron, Mark T. Quinn
Format: | Article |
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Diterbitkan: | MDPI AG 2020-10-01 |
Deskripsi
Little is known about the pharmacological activity of <i>Monarda fistulosa</i> L. essential oils. To address this issue, we isolated essential oils from the flowers and leaves of <i>M. fistulosa</i> and analyzed their chemical composition. We also analyzed the pharmacological effects of <i>M. fistulosa</i> essential oils on transient receptor potential (TRP) channel activity, as these channels are known targets of various essential oil constituents. Flower (MEO<sub>Fl</sub>) and leaf (MEO<sub>Lv</sub>) essential oils were comprised mainly of monoterpenes (43.1% and 21.1%) and oxygenated monoterpenes (54.8% and 77.7%), respectively, with a high abundance of monoterpene hydrocarbons, including <i>p</i>-cymene, γ-terpinene, α-terpinene, and α-thujene. Major oxygenated monoterpenes of MEO<sub>Fl</sub> and MEO<sub>Lv</sub> included carvacrol and thymol. Both MEO<sub>Fl</sub> and MEO<sub>Lv</sub> stimulated a transient increase in intracellular free Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) in TRPA1 but not in TRPV1 or TRPV4-transfected cells, with MEO<sub>Lv</sub> being much more effective than MEO<sub>Fl</sub>. Furthermore, the pure monoterpenes carvacrol, thymol, and β-myrcene activated TRPA1 but not the TRPV1 or TRPV4 channels, suggesting that these compounds represented the TRPA1-activating components of <i>M. fistulosa</i> essential oils. The transient increase in [Ca<sup>2+</sup>]<sub>i</sub> induced by MEO<sub>Fl</sub>/MEO<sub>Lv</sub>, carvacrol, β-myrcene, and thymol in TRPA1-transfected cells was blocked by a selective TRPA1 antagonist, HC-030031. Although carvacrol and thymol have been reported previously to activate the TRPA1 channels, this is the first report to show that β-myrcene is also a TRPA1 channel agonist. Finally, molecular modeling studies showed a substantial similarity between the docking poses of carvacrol, thymol, and β-myrcene in the binding site of human TRPA1. Thus, our results provide a cellular and molecular basis to explain at least part of the therapeutic properties of these essential oils, laying the foundation for prospective pharmacological studies involving TRP ion channels.