title: Effects of Catechol O-Methyl Transferase Inhibition on Anti-Inflammatory Activity of Luteolin Metabolites.
abstract: Although luteolin is known to have potent anti-inflammatory activities, much less information has been provided on such activities of its hepatic metabolites. Luteolin was subjected to hepatic metabolism in HepG2 cells either without or with catechol O-methyl transferase (COMT) inhibitor. To identify hepatic metabolites of luteolin without (luteolin metabolites, LMs) or with COMT inhibitor (LMs+CI), metabolites were treated by β-glucuronidase and sulfatase, and found that they were composed of glucuronide and sulfate conjugates of diosmetin in LMs or these conjugates of luteolin in LMs+CI. LMs and LMs+CI were examined for their anti-inflammatory activities on LPS stimulated Raw 264.7 cells. Expression of iNOS and production of nitric oxide and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were suppressed more effectively by the treatment with LMs+CI than LMs. Our data provide a new insight on possible improvement in functional properties of luteolin on target cells by modifying their metabolic pathway in hepatocytes.
authors.affiliation: Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Inst., Gyeonggi, 463-746, Republic of Korea.
authors.forename: Sang Keun
authors.initials: SK
authors.lastname: Ha
authors.affiliation: Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Inst., Gyeonggi, 463-746, Republic of Korea.
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Inst., Gyeonggi, 463-746, Republic of Korea.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Inst., Gyeonggi, 463-746, Republic of Korea.
authors.forename: Inwook
authors.initials: I
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D065098:Catechol O-Methyltransferase Inhibitors / Q000737:chemistry*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D047311:Luteolin / Q000737:chemistry*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D065098:Catechol O-Methyltransferase Inhibitors; D016207:Cytokines; D005419:Flavonoids; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D002394:Catechol O-Methyltransferase; D047311:Luteolin; C039602:diosmetin
keywords: catechol O-methyl transferase; inflammation; luteolin; metabolites