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Open Access 01-12-2012 | Research

1,8-cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1

Authors: Masayuki Takaishi, Fumitaka Fujita, Kunitoshi Uchida, Satoshi Yamamoto, Maki Sawada (Shimizu), Chihiro Hatai (Uotsu), Mayumi Shimizu, Makoto Tominaga

Published in: Molecular Pain | Issue 1/2012

Abstract

Background

Essential oils are often used in alternative medicine as analgesic and anti-inflammatory remedies. However, the specific compounds that confer the effects of essential oils and the molecular mechanisms are largely unknown. TRPM8 is a thermosensitive receptor that detects cool temperatures and menthol whereas TRPA1 is a sensor of noxious cold. Ideally, an effective analgesic compound would activate TRPM8 and inhibit TRPA1.

Results

We screened essential oils and fragrance chemicals showing a high ratio of human TRPM8-activating ability versus human TRPA1-activating ability using a Ca²⁺-imaging method, and identified 1,8-cineole in eucalyptus oil as particularly effective. Patch-clamp experiments confirmed that 1,8-cineole evoked inward currents in HEK293T cells expressing human TRPM8, but not human TRPA1. In addition, 1,8-cineole inhibited human TRPA1 currents activated by allyl isothiocyanate, menthol, fulfenamic acid or octanol in a dose-dependent manner. Furthermore, in vivo sensory irritation tests showed that 1,8-cineole conferred an analgesic effect on sensory irritation produced by TRPA1 agonists octanol and menthol. Surprisingly, 1,4-cineole, which is structurally similar and also present in eucalyptus oil, activated both human TRPM8 and human TRPA1.

Conclusions

1,8-cineole is a rare natural antagonist of human TRPA1 that has analgesic and anti-inflammatory effects possibly due to its inhibition of TRPA1.

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Title: 1,8-cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1
Authors: Masayuki Takaishi
Fumitaka Fujita
Kunitoshi Uchida
Satoshi Yamamoto
Maki Sawada (Shimizu)
Chihiro Hatai (Uotsu)
Mayumi Shimizu
Makoto Tominaga
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2012
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-8-86

At a glance: The STEP trials

Springer Medicine

1,8-cineole, a TRPM8 agonist, is a novel natural antagonist of human TRPA1

Abstract

Background

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusions

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