Carvacrol, a component of thyme oil, activates PPARalpha and gamma and suppresses COX-2 expression.
Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor superfamily and are involved in the control of COX-2 expression, and vice versa. Here, we show that COX-2 promoter activity was suppressed by essential oils derived from thyme, clove, rose, eucalyptus, fennel, and bergamot in cell-based transfection assays using bovine arterial endothelial cells. Moreover, from thyme oil, we identified carvacrol as a major component of the suppressor of COX-2 expression and an activator of PPARalpha and gamma. PPARgamma-dependent suppression of COX-2 promoter activity was observed in response to carvacrol treatment. In human macrophage-like U937 cells, carvacrol suppressed lipopolysaccharide-induced COX-2 mRNA and protein expression, suggesting that carvacrol regulates COX-2 expression through its agonistic effect on PPARgamma. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol.
Hotta
Mariko
M
Department of Food Science and Nutrition, Nara Women's University Nara 630-8506 Japan.
Nakata
Rieko
R
Katsukawa
Michiko
M
Hori
Kazuyuki
K
Takahashi
Saori
S
Inoue
Hiroyasu
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D000081007:Cymenes; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D039821:Monoterpenes / Q000494:pharmacology*; D009822:Oils, Volatile / Q000737:chemistry*; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D010938:Plant Oils / Q000737:chemistry*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D046930:Thymus Plant / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000081007:Cymenes; D008070:Lipopolysaccharides; D039821:Monoterpenes; D009822:Oils, Volatile; D047493:PPAR alpha; D047495:PPAR gamma; D010938:Plant Oils; C073316:carvacrol; D051546:Cyclooxygenase 2