title: Food Polyphenols Fail to Cause a Biologically Relevant Reduction of COX-2 Activity.
abstract: Epidemiologic studies show a correlation between the dietary intake of food polyphenols and beneficial health effects. Several in vitro studies indicate that the anti-inflammatory potential of polyphenols is, at least in part, mediated by a modulation of the enzymes of the arachidonic acid cascade, such as the prostaglandin forming cyclooxygenases (COXs). Evidence that this mode of action can be transferred to the situation in vivo is scarce. This study characterized effects of a subset of polyphenols on COX-2 expression and activity in vitro and compared the potency with known drugs. Next, the in vivo relevance of the observed in vitro effects was tested. Enzyme assays and incubations of polyphenols with the cancer cell line HCA-7 and lipopolysaccharide (LPS) stimulated primary monocytes support the hypothesis that polyphenols can effect COX-2 expression and activity in vitro. The effects were most pronounced in the monocyte assay for wogonin, apigenin, resveratrol and genistein with IC50 values of 1.5 μM, 2.6 μM, 2.8 μM and 7.4 μM. However, these values are 100- to 1000-fold higher in comparison to those of the known pharmaceuticals celecoxib, indomethacin and dexamethasone. In an animal model of LPS induced sepsis, pretreatment with polyphenols (i. p. 100 mg/kg bw) did not result in decreased plasma or tissue prostaglandin levels, whereas the positive control celecoxib effectively attenuated LPS induced prostaglandin formation. These data suggest that despite the moderate potency in vitro, an effect of polyphenols on COX-2 during acute inflammation is unlikely, even if a high dose of polyphenols is ingested.
authors.affiliation: University of Veterinary Medicine Hannover, Institute for Food Toxicology and Analytical Chemistry, Bischofsholer Damm 15, 30173 Hannover, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Willenberg
authors.affiliation: University of Veterinary Medicine Hannover, Institute for Food Toxicology and Analytical Chemistry, Bischofsholer Damm 15, 30173 Hannover, Germany.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Meschede
authors.affiliation: Department of Nephrology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Faikah
authors.initials: F
authors.lastname: Gueler
authors.affiliation: Department of Nephrology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Jang
authors.affiliation: Department of Nephrology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; Phenos GmbH, Feodor-Lynen-Straße 5, 30625 Hannover, Germany.
authors.forename: Nelli
authors.initials: N
authors.lastname: Shushakova
authors.affiliation: University of Veterinary Medicine Hannover, Institute for Food Toxicology and Analytical Chemistry, Bischofsholer Damm 15, 30173 Hannover, Germany; University of Wuppertal, Institute of Food Chemistry, Gaußstraße 20, 42119 Wuppertal, Germany.
authors.forename: Nils Helge
authors.initials: NH
authors.lastname: Schebb
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology; D000068579:Celecoxib / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D059808:Polyphenols; D013267:Stilbenes; D047310:Apigenin; D019833:Genistein; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D000077185:Resveratrol; D007213:Indomethacin