title: Metabolic Fate of Luteolin in Rats: Its Relationship to Anti-inflammatory Effect.
abstract: Luteolin is a naturally occurring flavone that reportedly has anti-inflammatory effects. Because most luteolin is conjugated following intestinal absorption, free luteolin is likely present at low levels in the body. Therefore, luteolin metabolites are presumably responsible for luteolin bioactivity. Here we confirmed that luteolin glucuronides, especially luteolin-3'-O-glucuronide, are the major metabolites found in plasma after oral administration of luteolin (aglycone) or luteolin glucoside (luteolin-7-O-glucoside) to rats. Luteolin-4'-O-glucuronide and luteolin-7-O-glucuronide were also detectable together with luteolin-3'-O-glucuronide in the liver, kidney, and small intestine. Next, we prepared these luteolin glucuronides and compared the anti-inflammatory effects of luteolin and luteolin glucuronides on gene expression in lipopolysaccharide-treated RAW264.7 cells. Luteolin glucuronides, especially luteolin-7-O-glucuronide, reduced expression of inflammatory genes in the cells, although their effects were weaker than those of luteolin. These results indicate that the active compound responsible for the anti-inflammatory effect of luteolin in vivo would be luteolin glucuronide and/or residual luteolin.
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University , Sendai, Miyagi 981-8555, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kure
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University , Sendai, Miyagi 981-8555, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University , Sendai, Miyagi 981-8555, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University , Sendai, Miyagi 981-8555, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Kato
authors.affiliation: Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University , Sendai, Miyagi 981-8555, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Kimura
authors.affiliation: Food Function Research Team, Saito Laboratory, Japan Food Research Laboratories , Ibaraki, Osaka 567-0085, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Miyagi Prefecture Watari Agricultural Promotion Center , Watari, Miyagi 989-2301, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Shoji
authors.affiliation: Industrial Technology Institute, Miyagi Prefectural Government , Sendai, Miyagi 981-3206, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Hatanaka
authors.affiliation: Department of Food Management, School of Food, Agricultural and Environmental Sciences, Miyagi University , Sendai, Miyagi 982-0215, Japan.
authors.forename: Tojiro
authors.initials: T
authors.lastname: Tsushida
authors.affiliation: Food and Biotechnology Innovation Project, New Industry Creation Hatchery Center (NICHe), Tohoku University , Sendai, Miyagi 980-8579, Japan.|Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University , Sendai, Miyagi 981-8555, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D047311:Luteolin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D015394:Molecular Structure; D000067996:RAW 264.7 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D047311:Luteolin
keywords: anti-inflammatory; luteolin; luteolin glucoside; luteolin glucuronide; metabolic fate