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Intestinal transport and oral bioavailability of the cancer preventive flavonoid 5,7‐dimethoxyflavone is greatly increased compared to its unmethylated analog chrysin
Author(s) -
Walle Thomas,
Wen Xia,
Kawamori Toshihiko,
Walle U. Kristina
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a731
Subject(s) - chrysin , bioavailability , glucuronidation , chemistry , flavones , cmax , pharmacology , pharmacokinetics , in vivo , oral administration , sulfation , caco 2 , flavonoid , biochemistry , in vitro , chromatography , medicine , biology , microsome , antioxidant , microbiology and biotechnology
A recent study in human hepatic preparations demonstrated that a methylated flavone, 5,7‐dimethoxyflavone (DMF), abundant in certain plants, such as the leaves of Piper caninum, has high metabolic stability compared to unmethylated flavones (Xenobiotica 36 :, 2006). This was tested further in human intestinal Caco‐2 cells and in vivo in rats. In Caco‐2 cells the apical to basolateral transport of DMF was dramatically greater than of its unmethylated analog chrysin (P app 23.3 versus 2.2 cm/s × 10 −6 ). There were no DMF metabolites, whereas chrysin showed extensive sulfation and glucuronidation. In the rat DMF and chrysin were given simultaneously by gavage (5 mg/kg of each). Plasma and tissue levels were measured by HPLC. Only DMF could be detected in plasma with a C max of 2.5 μM at 1 h after the dose. Also, only DMF could be reliably detected in liver, kidney and lung tissue. The liver showed the highest DMF accumulation, 16.5 μM at 1 h after the dose. The colon tissue had small amounts of DMF, whereas the fecal material within the colon contained high concentrations of chrysin, but only at 2–3 h after the dose. This study in Caco‐2 cells and in the rat demonstrates high intestinal transport and oral bioavailability for DMF. Such flavonoids may have great utility as cancer chemopreventive agents. Supported by NIH grant GM55561.