Citrus limonoids and flavonoids: Enhancement of Phase II detoxification enzymes and their potential in chemoprevention
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Enhancement of the detoxification pathway for the elimination of toxic electrophiles by the Phase-II enzymes (Glutathione S-transferase, GST; and NAD(P)H:quinine reductase, QR) is one means of cellular protection that may be anticarcinogenic. Effects of citrus limonoids (nomilin, limonin, aglycone mixtures) and flavonoids (hesperidin, naringin, and crude flavonoids mixture) were investigated in various tissues of mice. Three doses of 20 mg of citrus limonoids and flavonoids were given to 10-week-old female A/JOlaHsd mice over a period of one week. Limonoid aglycones were more effective inducers of GST activity than their respective glucosides. Nomilin and an aglycone mixture were the most potent inducers of GST. Citrus flavonoids showed the most significant induction of GST and QR in the stomach. The GST and QR induction by the limonoids and flavonoids appeared to be tissue-specific and related to the structures of the compounds. The enhanced level of phase-II enzymes by citrus flavonoids suggests their importance in chemoprevention. 2006 American Chemical Society.