Glucurono- and Sulfo-Conjugation of Kaempferol in Rat Liver Subcellular Preparations and Cultured Hepatocytes(Pharmacology)

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Glucurono- and sulfo-conjugation of kaempferol in rat liver preparations and cultured hepatocytes were studied using high-performance liquid chromatography (HPLC) with two distinctly different elution solvents. Kaempferol glucuronides and sulfates were produced by treating kaempferol with microsomes plus UDPGA or with cytosol plus PAPS, respectively. HPLC analysis of the conjugates revealed one major and three minor glucuronides with solvent A and one sulfate with solvent B. Kaempferol metabolites produced by cultured hepatocytes also consisted of four glucuronides and one minor sulfate, all of which corresponded to their respective in vitro-produced conjugates in the liver subcellular preparations. The relative proportion of kaempferol sulfate accounted for about 9% of the total conjugates in the cultured hepatocytes. The kinetic data on glucurono- and sulfo-conjugation of kaempferol by the liver subcellular preparations correlated well with the preferential production of kaempferol glucuronides in the cultured hepatocytes. Glucurono- and sulfo-conjugation of 3-, 5- and 7-OH flavones in the liver subcellular preparations were also kinetically characterized. 7-OH flavone was predominantly conjugated to form a glucuronide compared to 3- and 5-OH flavones. These data suggest that glucuronidation at the 7-OH position on the A-ring is a major metabolic pathway of kaempferol in hepatic cells.
公益社団法人日本薬学会の論文
2003-08-01