\u03b2-Eudesmol, an oxygenized sesquiterpene, stimulates appetite via TRPA1 and the autonomic nervous system

Kazuaki Ohara,Katsuya Nagai,Mikio Katayama,Kunitoshi Uchida,Makoto Tominaga,Takafumi Fukuda,Chika Takahashi,Rena Ohya,Yuko Ishida

doi:10.1038/s41598-017-16150-6

Abstract

Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel, which is activated by various noxious or irritant substances in nature. TRPA1 activators have been generally recognized as noxious, however, foods and beverages containing TRPA1 activators are preferably consumed; the reasons for this discrepancy are not well understood. We demonstrate that TRPA1 is involved in the stimulatory appetite control mechanism. β-Eudesmol is an oxygenated sesquiterpene contained in medicinal or edible plants which activates TRPA1. Oral administration of β-eudesmol brought significant increments in food intake in rats and elevated plasma ghrelin levels. Gastric vagal nerve activity (GVNA) has been reported to affect feeding behavior. In vivo electrophysiological measurement of GVNA revealed that oral-ingestion of β-eudesmol significantly increased GVNA. This GVNA elevation was eliminated by TRPA1 inhibitor (HC-030031) treatment prior to β-eudesmol administration. The physiological effects of β-eudesmol, for example, incremental increase in food intake, ghrelin elevation and activation of GVNA, were significantly reduced in TRPA1 knockout rats. Our results indicated that β-eudesmol stimulates an increase in appetite through TRPA1, and suggests why TRPA1 activator containing foods and beverages are preferably consumed.

Highlights

Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable, non-selective, cation channel which is mainly expressed in sensory nerve cells
Spices and seasoners containing TRPA1 activators have been preferably utilized in foods and beverages, and they are reported to stimulate the appetite[24], the mechanisms underlying appetite stimulation have not been elucidated
Our research suggests that appetite stimulation by spices or seasoners may involve gastric vagal nerve activity (GVNA) elevation, in part through TRPA1 activation

Summary

Introduction

Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable, non-selective, cation channel which is mainly expressed in sensory nerve cells. Compounds contained in the essential oils of plants are reported to be TRPA1 activators. The major components of essential oils are volatile terpenoids: menthol, contained in mint, and carvacrol, which accumulates in oregano, are reported to be activators of TRPA19,10. These TRPA1 activators have been empirically preferred as food and beverage ingredients, despite excess amounts being a noxious stimulus. Β-Eudesmol has been found in medicinal plants and physiological effects on mammals have been reported[12,13,14,15]: β-eudesmol has been shown to inhibit the nicotinic acetylcholine receptor at 100–200 μM13. Our results provide scientific evidence to explain the mechanism of preferable intake of TRPA1 activators in foods and beverages

Methods

Results

Conclusion