Use of the pig caecum model to mimic the human intestinal metabolism of hispidulin and related compounds.
Up to now, the metabolism of hispidulin (5,7,4'-trihydroxy-6-methoxyflavone), a potent ligand of the central human benzodiazepine receptor, has not been investigated. To elucidate the metabolism of hispidulin in the large intestine, its biotransformation by the pig caecal microflora was studied. In addition, the efficiency of the pig caecal microflora to degrade galangin (3,5,7-trihydroxyflavone), kaempferol (3,5,7,4'-tetrahydroxyflavone), apigenin (5,7,4'-trihydroxyflavone), and luteolin (5,7,3',4'-tetrahydroxyflavone) was investigated. Identification of the formed metabolites was performed by high-performance liquid chromatography (HPLC)-diode array detection, HPLC-electrospray ionization-tandem mass spectrometry, and high-resolution gas chromatography-mass spectrometry. The caecal microflora transformed hispidulin to scutellarein (5,6,7,4'-tetrahydroxyflavone), an effective alpha-glucosidase inhibitor, and 3-(4-hydroxyphenyl)-propionic acid; galangin to phenylacetic acid and phloroglucinol; kaempferol to 4-hydroxyphenylacetic acid, phloroglucinol, and 4-methylphenol; apigenin to 3-(4-hydroxyphenyl)-propionic acid and 3-phenylpropionic acid, and luteolin to 3-(3-hydroxyphenyl)-propionic acid, respectively. To elucidate to what extent different hydroxylation patterns on the B-ring influence the degradation degree of flavonoids, the conversions of galangin and kaempferol as well as that of apigenin and luteolin were compared with those of quercetin (3,5,7,3',4'-pentahydroxyflavone) and chrysin (5,7-dihydroxyflavone), respectively. Regardless of the flavonoid subclass, the presence of a hydroxy group at the 4'-position seems to be a prerequisite for fast breakdown. An additional hydroxy group at the B-ring did not affect the degradation degree.
Labib
Samira
S
Food Chemistry, University of Würzburg, Würzburg, Germany.
Hummel
Sylvia
S
Richling
Elke
E
Humpf
Hans-Ulrich
HU
Schreier
Peter
P
D000818:Animals; D047310:Apigenin / Q000378:metabolism; D001419:Bacteria / Q000378:metabolism*; D002432:Cecum / Q000382:microbiology*; D002851:Chromatography, High Pressure Liquid; D047309:Flavones / Q000378:metabolism* / Q000493:pharmacokinetics; D005419:Flavonoids / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D044949:Kaempferols / Q000378:metabolism; D007700:Kinetics; D047311:Luteolin / Q000378:metabolism; D023421:Models, Animal; D011794:Quercetin / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013552:Swine / Q000378:metabolism*
D047309:Flavones; D005419:Flavonoids; D044949:Kaempferols; C037032:galangin; C043561:chrysin; C006552:kaempferol; D047310:Apigenin; D011794:Quercetin; D047311:Luteolin; C055957:hispidulin; C458179:scutellarein