New natural agonists of the transient receptor potential Ankyrin 1 (TRPA1) channel

Abstract

The transient receptor potential (TRP) channels family are cationic channels involved in various physiological processes as pain, inflammation, metabolism, swallowing function, gut motility, thermoregulation or adipogenesis. In the oral cavity, TRP channels are involved in chemesthesis, the sensory chemical transduction of spicy ingredients. Among them, TRPA1 is activated by natural molecules producing pungent, tingling or irritating sensations during their consumption. TRPA1 can be activated by different chemicals found in plants or spices such as the electrophiles isothiocyanates, thiosulfinates or unsaturated aldehydes. TRPA1 has been as well associated to various physiological mechanisms like gut motility, inflammation or pain. Cinnamaldehyde, its well known potent agonist from cinnamon, is reported to impact metabolism and exert anti-obesity and anti-hyperglycemic effects. Recently, a structurally similar molecule to cinnamaldehyde, cuminaldehyde was shown to possess anti-obesity and anti-hyperglycemic effect as well. We hypothesized that both cinnamaldehyde and cuminaldehyde might exert this metabolic effects through TRPA1 activation and evaluated the impact of cuminaldehyde on TRPA1. The results presented here show that cuminaldehyde activates TRPA1 as well. Additionally, a new natural agonist of TRPA1, tiglic aldehyde, was identified and p-anisaldehyde confirmed.

The Beneficial Effects of Essential Oils in Anti-Obesity Treatment

“…Among the TRP channels, recent studies highlight in particular the role of the transient vanilloid receptor type 1 (TRPV1), the transient potential of the ankyrin receptor 1 (TRPA1), and the transient potential cation channel subfamily M (melastatin) member 8 (TRPM8) in the regulation of metabolism and energy homeostasis [ 107 , 108 ]. Many EOs, for example those extracted from bitter orange ( Citrus aurantiuum L) and Spearmint (Mentha spicata ), contain chemical compounds such as cinnamaldehyde, eugenol, and 1,8-cineole that, by stimulating these receptors, increase energy expenditure and thermogenesis and also reduce the sense of appetite and release of ghrelin [ 109 , 110 , 111 , 112 ].…”

TRP Channels as Molecular Targets to Relieve Cancer Pain

“…TRPA1, the only member of the TRPA subfamily, is a non-selective cation channel [ 12 , 13 ]. This channel has a calcium-binding domain and a voltage sensor in the C-terminal [ 14 ], 16 ankyrin repeat sequences in the N-terminal domain [ 8 , 15 ], and a putative selectivity filter placed at the entrance of the pore ( Figure 1 ).…”

Remedia Sternutatoria over the Centuries: TRP Mediation

“…In medieval Europe, cumin was used as a cheap(er) substitute for black pepper [ 28 ]. Legrand and his colleagues found that cuminal, the main active ingredient of cumin [ 29 ], specifically activates TRPA1 channels without affecting TRPV1 [ 30 ].…”