Key points are not available for this paper at this time.
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 PPARα and γ. PPARγ-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 PPARγ. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol. 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 PPARα and γ. PPARγ-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 PPARγ. These results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of carvacrol. Cyclooxygenase (COX), the rate-limiting enzyme in prostaglandin (PG) biosynthesis, has two isoforms, COX-1 and -2. COX-1 is constitutively expressed in most cells, whereas COX-2 is typically absent. However, COX-2 is induced by inflammatory stimuli such as endotoxins and lipopolysaccharide (LPS), suggesting that COX-2 plays a role in inflammation (1Smith W.L. Nutritionally essential fatty acids and biologically indispensable cyclooxygenases.Trends Biochem. Sci. 2008; 33: 27-33Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar, 2Simmons D.L. Botting R.M. Hla T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition.Pharmacol. Rev. 2004; 56: 387-437Crossref PubMed Scopus (1346) Google Scholar, 3Koki A. Khan N.K. Woerner B.M. Dannenberg A.J. Olson L. Seibert K. Edwards D. Hardy M. Isakson P. Masferrer J.L. Cyclooxygenase-2 in human pathological disease.Adv. Exp. Med. Biol. 2002; 507: 177-184Crossref PubMed Scopus (123) Google Scholar). Recent studies have shown that COX-2 is involved in not only inflammation but also circulatory homeostasis (4Dubois R.N. Abramson S.B. Crofford L. Gupta R.A. Simon L.S. Van De Putte L.B. Lipsky P.E. Cyclooxygenase in biology and disease.FASEB J. 1998; 12: 1063-1073Crossref PubMed Scopus (2225) Google Scholar, 5Morham S.G. Langenbach R. Loftin C.D. Tiano H.F. Vouloumanos N. Jennette J.C. Mahler J.F. Kluckman K.D. Ledford A. Lee C.A. et al.Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse.Cell. 1995; 83: 473-482Abstract Full Text PDF PubMed Scopus (1027) Google Scholar, 6Grosser T. Fries S. FitzGerald G.A. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities.J. Clin. Invest. 2006; 116: 4-15Crossref PubMed Scopus (843) Google Scholar). The peroxisome proliferator-activated receptors (PPARs) are members of a nuclear receptor family of ligand-dependent transcription factors (7Mangelsdorf D.J. Thummel C. Beato M. Herrlich P. Schutz G. Umesono K. Blumberg B. Kastner P. Mark M. Chambon P. The nuclear receptor superfamily: the second decade.Cell. 1995; 83: 835-839Abstract Full Text PDF PubMed Scopus (6088) Google Scholar). The PPAR subfamily comprises three isotypes, PPARα, β/δ, and γ, which play various roles in lipid and carbohydrate metabolism, cell proliferation and differentiation, and inflammation; they are considered molecular targets against lifestyle-related diseases (8Michalik L. Auwerx J. Berger J.P. Chatterjee V.K. Glass C.K. Gonzalez F.J. Grimaldi P.A. Kadowaki T. Lazar M.A. O’Rahilly S. et al.International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors.Pharmacol. Rev. 2006; 58: 726-741Crossref PubMed Scopus (798) Google Scholar, 9Sonoda J. Pei L. Evans R.M. Nuclear receptors: decoding metabolic disease.FEBS Lett. 2008; 582: 2-9Crossref PubMed Scopus (215) Google Scholar). The PGD2 metabolite 15-deoxy-Δ12,14 PGJ2 (15d-PGJ2) was identified as a potent natural ligand of PPARγ (10Forman B.M. Tontonoz P. Chen J. Brun R.P. Spiegelman B.M. Evans R.M. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma.Cell. 1995; 83: 803-812Abstract Full Text PDF PubMed Scopus (2731) Google Scholar, 11Kliewer S.A. Lenhard J.M. Willson T.M. Patel I. Morris D.C. Lehmann J.M. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation.Cell. 1995; 83: 813-819Abstract Full Text PDF PubMed Scopus (1869) Google Scholar). Previously, we reported that 15d-PGJ2 suppressed LPS-induced expression of COX-2 in differentiated, macrophage-like U937 cells, but not in vascular endothelial cells, and that the expression of COX-2 was regulated by a negative feedback loop mediated through PPARγ, especially in macrophages (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar). Likewise, the PPARα agonist fenofibrate inhibited interleukin-1-induced COX-2 expression in smooth muscle cells (13Staels B. Koenig W. Habib A. Merval R. Lebret M. Torra I.P. Delerive P. Fadel A. Chinetti G. Fruchart J.C. et al.Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators.Nature. 1998; 393: 790-793Crossref PubMed Scopus (1056) Google Scholar). These findings indicate that PPARs participate in cell type-specific control of COX-2 expression. Resveratrol, a phytoalexin and antioxidant polyphenolic compound found in red wine and various plant products, has long been suspected to have cardioprotective effects and to be a contributor to the so-called “French paradox” (i.e., the relatively low incidence of coronary heart disease in France compared to other developed countries with comparable diets; 14St. Leger A.S. Cochrane A.L. Moore F. Factors associated with cardiac mortality in developed countries with particular reference to the consumption of wine.Lancet. 1979; 1: 1017-1020Abstract PubMed Scopus (633) Google Scholar, 15Renaud S. De Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease.Lancet. 1992; 339: 1523-1526Abstract PubMed Scopus (3183) Google Scholar, 16Ferrières J. The French paradox: lessons for other countries.Heart. 2004; 90: 107-111Crossref PubMed Scopus (225) Google Scholar). We demonstrated that resveratrol suppressed COX-2 expression in 184B5/HER-transformed mammary epithelial cells (17Subbaramaiah K. Chung W.J. Michaluart P. Telang N. Tanabe T. Inoue H. Jang M. Pezzuto J.M. Dannenberg A.J. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells.J. Biol. Chem. 1998; 273: 21875-21882Abstract Full Text Full Text PDF PubMed Scopus (749) Google Scholar), activated PPARα and γ in cell-based reporter assays using bovine arterial endothelial cells (BAEC), and protected the brain against ischemic stroke in mice through a PPARα-dependent mechanism (18Inoue H. Jiang X. Katayama T. Osada S. Umesono K. Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice.Neurosci. Lett. 2003; 352: 203-206Crossref PubMed Scopus (228) Google Scholar). Similarly, polyphenolic compounds such as apigenin, chrysin (19Liang Y.C. Huang Y.T. Tsai S.H. Lin-Shiau S.Y. Chen C.F. Lin J.K. Suppression of inducible cyclooxygenase and inducible nitric oxide synthase by apigenin and related flavonoids in mouse macrophages.Carcinogenesis. 1999; 20: 1945-1952Crossref PubMed Scopus (501) Google Scholar, 20Woo K.J. Jeong Y.J. Inoue H. Park J.W. Kwon T.K. Chrysin suppresses lipopolysaccharide-induced cyclooxygenase-2 expression through the inhibition of nuclear factor for IL-6 (NF-IL6) DNA-binding activity.FEBS Lett. 2005; 579: 705-711Crossref PubMed Scopus (132) Google Scholar), and humulon (21Yamamoto K. Wang J. Yamamoto S. Tobe H. Suppression of cyclooxygenase-2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid.FEBS Lett. 2000; 465: 103-106Crossref PubMed Scopus (61) Google Scholar) suppress COX-2 expression, and these compounds activate PPARα and/or γ (22Liang Y.C. Tsai S.H. Tsai D.C. Lin-Shiau S.Y. Lin J.K. Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-gamma by flavonoids in mouse macrophages.FEBS Lett. 2001; 496: 12-18Crossref PubMed Scopus (206) Google Scholar, 23Yajima H. Ikeshima E. Shiraki M. Kanaya T. Fujiwara D. Odai H. Tsuboyama-Kasaoka N. Ezaki O. Oikawa S. Kondo K. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance.J. Biol. Chem. 2004; 279: 33456-33462Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar). The suppression of COX-2 expression and the agonistic activity for PPARs are useful in evaluating the function of food-related components in lifestyle-related diseases. Similar to the case of 15d-PGJ2, it is possible that COX-2 expression is regulated by PPAR agonism exerted by chemical components in In we derived from various and found that essential oils have COX-2 Moreover, we identified from the essential of thyme, as a major suppressor of COX-2 expression and activator of In PPARγ-dependent suppression of COX-2 promoter activity was observed in response to that carvacrol regulates COX-2 expression through its agonistic effect on PPARγ. clove, eucalyptus, fennel, and chemical components of thyme oils from and oils from and oils from and oils from and U937 cells H. T. S. C. Tanabe T. The response plays an essential role in the expression of the human synthase 2 gene in U937 Lett. PubMed Scopus Google Scholar) and H. C. M. T. and of cyclooxygenase-2 expression by in vascular endothelial Biol. 2002; PubMed Scopus Google Scholar) in and with and U937 cells with and to for which they with and for H. Tanabe T. role of the nuclear factor in the by lipopolysaccharide and suppression by of cyclooxygenase-2 in U937 1998; PubMed Scopus Google Scholar). from U937 cells was using the and for gene expression by to using was using The for of COX-2 and and The by of for and for of COX-2 mRNA to of to in The with human COX-2 and using an to the was using a and using In the COX-2 promoter using (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar). of COX-2 reporter H. T. S. C. Tanabe T. The response plays an essential role in the expression of the human synthase 2 gene in U937 Lett. PubMed Scopus Google Scholar), human expression and of for a control expression was of and and activity was to the in (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar). the PPARα activation with of reporter S.A. Umesono K. D.J. R.A. Evans R.M. of and peroxisome through of 1992; PubMed Scopus Google Scholar), of human PPARα expression and of as (18Inoue H. Jiang X. Katayama T. Osada S. Umesono K. Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice.Neurosci. Lett. 2003; 352: 203-206Crossref PubMed Scopus (228) Google Scholar). the and γ activation expression and for the transfection of the human PPARα expression was by The thyme was by using a A and was with as a a of was in and of was The was The was for 2 and to a of The was The from using The of the components are shown in was also by using a to a The the as The was The components of thyme identified by using the by the of the for and The human COX-2 promoter nuclear nuclear factor for expression, and response H. C. S. Tanabe T. of human gene by lipopolysaccharide and phorbol in vascular endothelial cells. of both nuclear factor for expression and response Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar). Previously, transfection assays using the COX-2 reporter and expression that of the COX-2 gene by 15d-PGJ2 (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar), the of PPARγ in the of COX-2 expression by we oils derived from of and found that LPS-induced COX-2 promoter activity was suppressed by thyme and bergamot oils in of activity these oils are essential whereas suppression of COX-2 promoter activity was found with oils was the suppressor these essential oils and suppression of LPS-induced COX-2 promoter activity Previously, we reported that induced COX-2 promoter activity in the reporter H. C. S. Tanabe T. of human gene by lipopolysaccharide and phorbol in vascular endothelial cells. of both nuclear factor for expression and response Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar). shown in induced COX-2 promoter activity that is useful for natural from various is to be a potent protein activator M. K. K. activation of protein by phorbol Biol. Chem. Full Text PDF PubMed Google Scholar). Previously, we also reported that with and induced COX-2 promoter activity H. C. S. Tanabe T. of human gene by lipopolysaccharide and phorbol in vascular endothelial cells. of both nuclear factor for expression and response Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar), that activation of is involved in COX-2 promoter activity in a of treatment. a of J.M. J.M. J. J.P. is a potent and of protein PubMed Scopus Google Scholar), not suppress the LPS-induced promoter activity of COX-2 suggesting that the suppression by essential oils such as thyme is not inhibition of suppression of COX-2 promoter activity by thyme and the effects of on promoter with with and as an control for the the cells for with thyme and and In a second the cells for with with in the with In both the cells and for both and The results are as which against the and as the compared with cells with by an A natural ligand for PPARγ, 15d-PGJ2, suppressed the LPS-induced COX-2 mRNA expression in macrophage-like U937 cells (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar). Resveratrol suppressed COX-2 mRNA expression (17Subbaramaiah K. Chung W.J. Michaluart P. Telang N. Tanabe T. Inoue H. Jang M. Pezzuto J.M. Dannenberg A.J. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells.J. Biol. Chem. 1998; 273: 21875-21882Abstract Full Text Full Text PDF PubMed Scopus (749) Google Scholar) and also activated PPARα and γ in cell-based using (18Inoue H. Jiang X. Katayama T. Osada S. Umesono K. Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice.Neurosci. Lett. 2003; 352: 203-206Crossref PubMed Scopus (228) Google Scholar). using we the activation of PPARs by the essential oils that suppressed LPS-induced COX-2 promoter activity that thyme, rose, clove, and bergamot oils PPARα agonistic activity and that thyme also PPARγ agonistic In the control of such as and PPARα, β/δ, and γ agonistic thyme activated PPARα and γ with the the for suppression of the LPS-induced COX-2 promoter activity was observed a control suppressed LPS-induced COX-2 promoter activity in in the of the PPARγ In we found that PPARγ expression in U937 cells (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar). the effect of the PPARγ agonist 15d-PGJ2 on COX-2 expression is potent that of an agonist of the which is by (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar). We also the effects of on the expression of PPARs and COX-2 in U937 cells and found that PPARγ mRNA was suppressed in response to activation of PPARα and PPARγ by thyme with with and as an control for the the cells for with thyme and The cells and for both and The results are as which against the and as the compared with cells with by an We for in thyme that involved in the suppression of LPS-induced COX-2 promoter activity and activation of PPARα and γ. was by and major for of the oil, the of the carvacrol and compounds for effects on LPS-induced COX-2 promoter activity a of carvacrol and suppressed promoter activity by and shown in COX-2 promoter activity was suppressed to by thyme oil, which carvacrol and the suppression of COX-2 promoter activity by carvacrol and suppression by and that carvacrol is the major component of thyme involved in the suppression of the LPS-induced COX-2 promoter the other COX-2 promoter activity was only suppressed in the of PPARγ expression suppression was in the of the PPARγ expression in that suppression was PPARγ In the control carvacrol effect on COX-2 promoter activity in the transfection using and effect on COX-2 mRNA in U937 cells we PPAR activated PPARα and γ the which the suppression of COX-2 promoter activity was observed These carvacrol are to which PPARα and γ observed in response to thyme Moreover, carvacrol induced the mRNA expression of the PPARα-dependent gene in U937 cells These results indicate that carvacrol is both a suppressor of COX-2 promoter activity and an activator of PPARα and suppression of COX-2 promoter activity in response to carvacrol. with with the human PPARγ expression the expression and as an control for the the cells for with with carvacrol and The cells and for both and The results are as which against the compared with and by an of PPARα and PPARγ in response to carvacrol and with with and as an control for the the cells for with The cells and for both and The results are as which to the compared with cells with by an In not suppress LPS-induced COX-2 promoter whereas a of Similarly, but not activated PPARα and γ In carvacrol and but not activated These results that the of carvacrol is essential for both the suppression of COX-2 promoter activity and the activation of PPARα and γ. we carvacrol suppressed COX-2 mRNA and protein expression in macrophage-like U937 cells. LPS-induced COX-2 mRNA and protein expression was suppressed by carvacrol to in and in suppression of LPS-induced COX-2 protein expression is with the results of the COX-2 reporter assays The LPS-induced expression of COX-2 mRNA was suppressed to by with carvacrol but was not suppressed in response to carvacrol may be in to the of COX-2 mRNA the and J.M. J.M. J. J.P. is a potent and of protein PubMed Scopus Google Scholar, T. Inoue H. of the of cyclooxygenase-2 gene in its through the Sci. 2004; PubMed Scopus Google Scholar). The of COX-2 mRNA has of the which is involved in the regulated of COX-2 mRNA by T. Inoue H. of the of cyclooxygenase-2 gene in its through the Sci. 2004; PubMed Scopus Google Scholar). we found that carvacrol is involved in the control of COX-2 mRNA on reporter assays using the of COX-2 carvacrol suppressed not only promoter activity in with but also LPS-induced COX-2 mRNA and protein expression in U937 cells of COX-2 protein expression in response to carvacrol in macrophage-like U937 cells. U937 cells for with in the of the of carvacrol. by and a with for COX-2 and The expression of COX-2 was against that of and the of COX-2 protein induced by was as The results the of three compared with cells with by an The of lifestyle-related such as cardiovascular and is of have been studies on the of natural in and In resveratrol in red wine is of the most of the and its has C.A. I. Resveratrol as an and and 2005; PubMed Scopus Google Scholar, of the in Rev. 2005; Scopus Google Scholar). We have on COX-2 (17Subbaramaiah K. Chung W.J. Michaluart P. Telang N. Tanabe T. Inoue H. Jang M. Pezzuto J.M. Dannenberg A.J. Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells.J. Biol. Chem. 1998; 273: 21875-21882Abstract Full Text Full Text PDF PubMed Scopus (749) Google Scholar) and PPARs (18Inoue H. Jiang X. Katayama T. Osada S. Umesono K. Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice.Neurosci. Lett. 2003; 352: 203-206Crossref PubMed Scopus (228) Google Scholar) as possible molecular targets of resveratrol in lifestyle-related have studied and K.J. C. A. G. K. et and of mice on a 2006; PubMed Scopus Google Scholar, M. C. H. C. F. N. J. P. P. et function and against metabolic disease by and 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). that humulon (21Yamamoto K. Wang J. Yamamoto S. Tobe H. Suppression of cyclooxygenase-2 gene transcription by humulon of beer hop extract studied with reference to glucocorticoid.FEBS Lett. 2000; 465: 103-106Crossref PubMed Scopus (61) Google Scholar, 23Yajima H. Ikeshima E. Shiraki M. Kanaya T. Fujiwara D. Odai H. Tsuboyama-Kasaoka N. Ezaki O. Oikawa S. Kondo K. Isohumulones, bitter acids derived from hops, activate both peroxisome proliferator-activated receptor alpha and gamma and reduce insulin resistance.J. Biol. Chem. 2004; 279: 33456-33462Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar) and apigenin (22Liang Y.C. Tsai S.H. Tsai D.C. Lin-Shiau S.Y. Lin J.K. Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-gamma by flavonoids in mouse macrophages.FEBS Lett. 2001; 496: 12-18Crossref PubMed Scopus (206) Google Scholar), as as suppress COX-2 expression and activate we essential for effects on COX-2 and PPARs and found that a major component of thyme oil, was is that carvacrol PPARα and γ and suppresses LPS-induced COX-2 protein expression in the Moreover, PPARγ-dependent suppression of COX-2 promoter activity was observed in response to carvacrol which is with that 15d-PGJ2, a potent natural ligand of PPARγ, suppressed LPS-induced COX-2 expression in macrophage-like U937 cells and that the expression of COX-2 was regulated by a negative feedback loop mediated through PPARγ (12Inoue H. Tanabe T. Umesono K. Feedback control of cyclooxygenase-2 expression through PPARgamma.J. Biol. Chem. 2000; 275: 28028-28032Abstract Full Text Full Text PDF PubMed Scopus (271) Google Scholar). it is that carvacrol regulates COX-2 expression, in its agonistic effect on PPARγ. of the of carvacrol to suppress COX-2 promoter activity and activate we the possible of a associated with carvacrol. we results using of carvacrol both and these that a was to the carvacrol is the of effects on the the of the molecular of carvacrol is that of other PPAR which may be of the for its relatively activation of We also observed activation of with carvacrol and both of which an in activity In carvacrol and and in PPARα and and in PPARγ suggesting that carvacrol and activate these factors in a acids are considered to be for PPARs compared with In the of fatty which and both and of the cells to PPAR A mechanism may be in the activation of PPARs by carvacrol and other chemical components in essential carvacrol was reported to be an agonist of receptor a expressed in the and H. M. J.C. thyme and and activate 2006; PubMed Scopus Google Scholar, K. M.A. G. J. G. H. of J. PubMed Scopus Google Scholar). The of carvacrol for is to the for COX-2 and PPARs in Moreover, but not is also an agonist of suggesting a for a which is also to results on the effects on COX-2 and PPARs of activate and on the and may be We demonstrated that LPS-induced COX-2 promoter activity was suppressed by not only thyme but also clove, rose, eucalyptus, fennel, and bergamot oils is that of PPARs not found with but was a for activation by thyme, clove, rose, eucalyptus, and oils These results may indicate that natural in essential oils as COX-2 but not PPAR that components as of the chemical compounds in these essential oils is In we identified a chemical component of thyme oil, as a suppressor of COX-2 and activator of PPARα and γ. most essential oils such as thyme have a of in and of are not for of the which and properties Biological and of carvacrol and carvacrol essential 2008; PubMed Scopus Google Scholar). results may be important in understanding the antiinflammatory and antilifestyle-related disease properties of studies in be to the of using reporter assays for COX-2 and PPARs may be for the of food-related The and for with bovine arterial endothelial cell cyclooxygenase lipopolysaccharide 15-deoxy-Δ12,14 PGJ2 prostaglandin protein peroxisome proliferator-activated receptor receptor
Hotta et al. (Sat,) studied this question.
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