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	John A Manthey, Philip Bendele
Journal	Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 56 Issue 20 Pg. 9399-403 (Oct 22 2008) ISSN: 1520-5118 [Electronic] United States
PMID	18816060 (Publication Type: Journal Article)
Chemical References	Anti-Inflammatory Agents Flavonoids Lipopolysaccharides Plant Extracts Tumor Necrosis Factor-alpha 3,3',4',5,6,7,8-heptamethoxyflavone Carrageenan
Topics	Animals Anti-Inflammatory Agents (administration & dosage, metabolism) Carrageenan (immunology) Citrus (chemistry) Disease Models, Animal Dose-Response Relationship, Drug Drug Administration Routes Edema (chemically induced, drug therapy, metabolism) Flavonoids (administration & dosage, metabolism) Humans Inflammation (chemically induced, drug therapy, metabolism) Lipopolysaccharides (immunology) Male Mice Plant Extracts (administration & dosage, metabolism) Rats Rats, Sprague-Dawley Tumor Necrosis Factor-alpha (blood)

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