Carvacrol, a component of thyme oil, activates PPARα and γ and suppresses COX-2 expression

Mariko Hotta,Rieko Nakata,Michiko Katsukawa,Kazuyuki Hori,Saori Takahashi,Hiroyasu Inoue

doi:10.1194/jlr.m900255-jlr200

Abstract

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.

Highlights

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis
We evaluated commercially available oils derived from 21 kinds of plants, each at 0.01% concentration, and found that LPS-induced COX-2 promoter activity was suppressed by thyme (65%), clove (40%), rose (30%), eucalyptus (25%), fennel (22%), and bergamot oils (21%), in descending order of activity (Fig. 1)
We reported that combined treatment with treated with nM 12-Otetradecanoylphorbol-13-acetate (TPA) and LPS synergistically induced COX-2 promoter activity [28], indicating that activation of protein kinase C (PKC) is involved in inducing COX-2 promoter activity in a manner independent of LPS treatment

Summary

Introduction

Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis. 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.—Hotta, M., R. The PPAR subfamily comprises three isotypes, PPAR␣, ␤/␦, and ␥, which play various roles in lipid and carbohydrate metabolism, cell proliferation and differentiation, and inflammation; they are considered molecular targets against lifestyle-related diseases [8, 9]. The PPAR␣ agonist fenofibrate inhibited interleukin-1-induced COX-2 expression in smooth muscle cells [13] These findings indicate that PPARs participate in cell type-specific control of COX-2 expression

Methods

Results

Conclusion