title: Anti-inflammatory activity of an orange peel polymethoxylated flavone, 3',4',3,5,6,7,8-heptamethoxyflavone, in the rat carrageenan/paw edema and mouse lipopolysaccharide-challenge assays.
abstract: The anti-inflammatory properties of 3',4',3,5,6,7,8-heptamethoxyflavone (HMF), a citrus polymethoxylated flavone, were studied in the bacterial lipopolysaccharide (LPS)-challenge/tumor necrosis factor-alpha (TNFalpha) response in mice and in the carrageenan/paw edema assay in rats. In each of these trials, HMF administered by intraperitoneal (ip) injection exhibited anti-inflammatory activity, whereas HMF administered orally (po) produced no effects. The inhibition observed in the LPS-challenge/TNFalpha assay correlated with the HMF levels in the blood sera of mice dosed (ip) with either 33 or 100 mg/kg body weight. Low levels of HMF (0.035 +/- 0.024 ppm) were detected in the blood sera of mice dosed orally [100 mg of HMF (suspended in vegetable oil)/kg], whereas ip injection led to higher levels (0.517 +/- 0.051 ppm). This may account for the different levels of anti-inflammatory effects observed in mice following ip vs oral HMF administration. HMF metabolites, including a number of mono- and di-demethylated HMF metabolites and their glucuronic acid conjugates, were also detected, but results of these studies suggest that the glucuronidated metabolites of HMF are inactive in these inflammation models.
authors.affiliation: U.S. Citrus and Subtropical Products Laboratory, Agricultural Research Service, U.S. Department of Agriculture, 600 Avenue S, Northwest, Winter Haven, Florida 33881, USA. John.Manthey@ars.usda.gov
authors.forename: John A
authors.initials: JA
authors.lastname: Manthey
authors.forename: Philip
authors.initials: P
authors.lastname: Bendele
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000378:metabolism; D002351:Carrageenan / Q000276:immunology; D002957:Citrus / Q000737:chemistry*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D005419:Flavonoids / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D010936:Plant Extracts / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D008070:Lipopolysaccharides; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C059294:3,3',4',5,6,7,8-heptamethoxyflavone; D002351:Carrageenan