Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels

Xu, Haoxing; Delling, Markus; Jun, Janice; Clapham, David E.

doi:10.1038/nn1692

Cited by 566 publications

(564 citation statements)

References 36 publications

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“…Among these proteins, receptors belonging to the cation channels in the TRP family also act as cellular sensors. In cell cultures, thymol activates the thermal/ irritant-responsive TRPA1 (Lee et al, 2008;Kaji et al, 2011), the warmth-sensing TRPV3 (Xu et al, 2006) and the coldsensing TRPM8 (Ortar et al, 2012). Activation of TRPA1 by luminal stimuli induces anion secretion in colon enterocytes (Kaji et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Colombo

Priori

Gandolfi

et al. 2014

Animal

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Thymol is the most common molecule in thyme and has been proposed as an oral alternative to antibiotics in the feed of pigs and broilers. The knowledge of the in vivo physiological effects of thymol on tissues is limited, particularly its impact on the gastric mucosa, where it is primarily absorbed when it is orally supplied. In this study, thymol (TH, 50 mg/ kg BW) or a placebo (CO) was introduced directly into the stomach of 8 weaned pigs that were slaughtered 12 h later and sampled for gastric oxyntic and pyloric mucosa. The analysis of whole transcript expression was performed using Affymetrix © Porcine Gene 1.1 ST array strips. Affymetrix Transcripts IDs were associated with 13 406 human gene names based on Sus scrofa Ensemble. Gene Set Enrichment Analysis was performed, comparing TH and CO pigs. For each gene set, the normalized enrichment score (NES) was defined as significant when the false discovery rate % was <25 and the P-value of NES was <0.05. In response to TH, 72 and 19 gene sets were significantly enriched in the oxyntic and pyloric mucosa, respectively. Several gene sets involved in mitosis and its regulation ranked near the top, primarily in the oxyntic mucosa; the gene set DIGESTION ranked first and ninth in the pyloric and oxyntic mucosa, respectively. Within this group, somatostatin (SST), SST receptors, peptide transporter 1 (SLC15A1) and calpain 9 (gastrointestinal tract-specific calpain) were the most strongly upregulated genes. Thymol reduced the enrichment of 120 and 59 gene sets in the oxyntic and pyloric mucosa, respectively. Several gene sets related to ion transport and channeling and aqueous pores across membranes, including short transient receptor potential (TRP) channel 4, potassium voltage-gated channel members 1 and 2, and ryanodine receptors 2 and 3, were less enriched. The downregulation of these genes sensitive to thymol in vitro could depend on the thymol dose and contact with the gastric tissues that causes an adaptive response with their reduced activation. Conversely, the activation of the TRPA1 gene (ranked 1072 and 128 among all the genes in the oxyntic and pyloric mucosa, respectively) indicates the involvement of another TRP-regulating cellular calcium storage. In conclusion, the stimulation of gastric proliferative activity and the control of digestive activity by thymol can influence positively gastric maturation and function in the weaned pigs. These properties should be considered in addition to thymol's antimicrobial properties when supplementation of this molecule in feed is evaluated.

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Section: Discussionmentioning

confidence: 99%

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Colombo

Priori

Gandolfi

et al. 2014

Animal

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“…Interestingly, skin allergen, such as eugenol, is an activator of TRPV3. Stimulation of primary keratinocytes by eugenol and other chemical allergens, presumably through activation of TRPV3, induces the release of the inflammatory cytokine interleukin-1α [14,23], which has been shown to enhance mast cell proliferation in the presence of fibroblasts [24]. Thus, enhanced TRPV3 function can indeed explain the allergic and inflammatory manifestations displayed by the affected skin tissues of the mutant rodents.…”

Section: Discussionmentioning

confidence: 99%

“…TRPV4 is activated by osmolarity changes [10,11], by the epoxygenase products of arachidonic acid [12], and by bisandrographolide from the medicinal plant, Andrographis Paniculata [13]. TRPV3 is activated by a number of plant extracts, such as camphor [8], carvacrol (from oregano) eugenol (from clove), and thymol (from thyme) [14]. All these compounds have low affinities to TRPV3 and are nonspecific in that they activate other TRP channels as well.…”

Section: Introductionmentioning

confidence: 99%

“…Nonetheless, their uses as flavor enhancers, skin irritants or sensitizers are consistent with the predominant expression of TRPV3 in skin as well as oral and nasal epithelia. It has been speculated that TRPV3 may be involved in the response to allergens exposed to the body surface [14]. However, an endogenous ligand has yet to be found for TRPV3.…”

Section: Introductionmentioning

confidence: 99%

“…However, an endogenous ligand has yet to be found for TRPV3. Another chemical commonly used to activate TRPV3 is 2-aminoethoxydiphenyl borate (2APB) [7,[14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

Xiao¹,

Tian²,

Tang³

et al. 2008

Cell Calcium

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SummaryTRPV3 is a non-selective cation channel activated by warm to hot temperatures. In rodents, TRPV3 is highly expressed in basal keratinocytes of skin and oral/nasal epithelia. TRPV3 knockout mice showed impaired responses to innocuous and noxious heat but otherwise normal appearance and reactions to many sensory modalities. However, point mutations of TRPV3 at Gly573 to Ser and Cys have recently been linked to autosomal dominant hairless phenotypes and spontaneous dermatitis in mice and rats, implicating an important role for TRPV3 in alopecia and skin diseases. Exactly how the mutations affect TRPV3 function was unexplained. Here we show that both G573S and G573C mutations of murine TRPV3 are constitutively active in heterologous systems. In HEK293 cells, expression of the TRPV3 mutants causes cell death. In Xenopus oocytes, the constitutively active mutant channel is irresponsive to thermal and chemical stimuli but it reduces the temperature threshold and enhances the responses to heat and TRPV3 agonists of the wild type channel when they are co-expressed. We conclude that the G573S and G573C substitutions render the TRPV3 channel spontaneously active under normal physiological conditions, which in turn alters ion homeostasis and membrane potentials of skin keratinocytes, leading to hair loss and dermatitis-like skin diseases.

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Transient receptor potential A1 channels regulate epithelial cell barriers formed by MDCK cells

et al. 2016

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Edited by Maurice MontalTransient receptor potential A1 channels are well-known as chemosensors in neuronal cells. However, recent studies also point to non-neuronal functions in epithelia. Here, we show that TRPA1 channels are expressed in epithelial MDCK II cells and contribute to Ca 2+ influx and whole-cell currents after stimulation with AITC. Stimulation of TRPA1 channels induced an immediate reduction of the transepithelial resistance of MDCK II cell layers that was blocked by the TRPA1 antagonist HC-030031. The present data provide strong evidence for a new role of TRPA1 channels in regulating the tightness of epithelial cell barriers.

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Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels

Cited by 566 publications

References 36 publications

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

Effect of free thymol on differential gene expression in gastric mucosa of the young pig

The TRPV3 mutation associated with the hairless phenotype in rodents is constitutively active

Transient receptor potential A1 channels regulate epithelial cell barriers formed by MDCK cells

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