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Papers In Press, published online ahead of print January 1, 2010
J. Lipid Res., doi:10.1194/jlr.M900255-JLR200

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Journal of Lipid Research, Vol. 51, 132-139, January 2010
Copyright © 2010 by American Society for Biochemistry and Molecular Biology

Carvacrol, a component of thyme oil, activates PPAR and and suppresses COX-2 expression^[S]

Mariko Hotta^*, Rieko Nakata^*, Michiko Katsukawa^*, Kazuyuki Hori, Saori Takahashi and Hiroyasu Inoue^1,*

^* Department of Food Science and Nutrition, Nara Women's University Nara 630-8506 Japan
Department of Bioengineering, Akita Research Institute of Food and Brewing 010-1623 Japan

¹ To whom correspondence should be addressed. e-mail: inoue{at}cc.nara-wu.ac.jp

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 PPAR and . PPAR-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 PPAR. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol.

Supplementary key words cyclooxygenase • peroxisome proliferator-activated receptor • thymol • essential oil

Abbreviations: BAEC, bovine arterial endothelial cell; COX, cyclooxygenase; FID, flame ionization detection; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; LPS, lipopolysaccharide; 15d-PGJ₂, 15-deoxy-^12,14 PGJ₂; PG, prostaglandin; PKC, protein kinase C; PPAR, peroxisome proliferator-activated receptor; TPA, 12-O-tetradecanoylphorbol-13-acetate; TRP, transient receptor potential

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