環境変異原研究
Online ISSN : 1880-7054
Print ISSN : 0910-0865
ISSN-L : 0910-0865
第15回公開シンポジウム「食べ物によるがん予防戦略を考える-生活環境中の植物成分の抗変異・抗発がん作用とそのメカニズム-」
フラボノイド類の血中代謝物と局所における有効性
下位 香代子
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ジャーナル フリー

2004 年 26 巻 3 号 p. 241-246

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Recent studies on the bioavailability, pharmacokinetics and metabolism of flavonoids which are common dietary components of vegetables, fruits, wine, and tea have largely focused on evaluating their in vivo functional activities and their roles in the chemoprevention of diseases, including cancer, atherosclerosis, and others. A number of studies have reported that the absorbed flavonoids are primarily metabolized to the glucuronide and/or sulfate conjugates in vivo, which then circulate in the blood and are released into the bile and urine for excretion. It remains unknown, however, whether these conjugates still retain biological functions in vivo as their aglycones do. Notably, a glucuronided metabolite of quercetin was earlier reported to possess antioxidant activity and to prevent vascular smooth muscle cell hypertrophy induced by angiotensin II. We thus set out to study the effects of quercetin conjugates on TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) by using an ELISA detection method. We found that quercetin-3-glucuronide and quercetin-3-sulfate failed to show suppressive effects. Moreover, quercetin-3-glucuronide showed no antiproliferative effects in MCF-7 mammary tumor cells. Accordingly, these results suggest that deconjugation is required for a quercetin glucuronide to exert its effects. We found that β-glucuronidase released from neutrophils and certain injured cells can hydrolyze glucuronidated flavonoids to free aglycones when inflammation occurs. In addition, we also found that incubation of endothelial cells with cytokines such as IL-1α resulted in an increased permeability to glucuronides. Therefore, it is suggested that conjugated flavonoids may pass through the vascular monolayers and are then converted to free aglycones by the hydrolyzing enzymes released from inflammatory cells or tissue cells to exert their biological activity at the inflammation site. Hence, it is our belief that the conjugated flavonoids in circulation may still play an important role as chemopreventive agents at the early stage of an inflammatory disease process.

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© 2004 日本環境変異原学会
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