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Tissue distribution in mice and metabolism in murine and human liver of apigenin and tricin, flavones with putative cancer chemopreventive properties

By Hong Cai, David J. Boocock, William P. Steward and Andreas J. Gescher


This is the author's own draft. 'The original publication is available at' \ud The flavones apigenin and tricin, which occur in leafy vegetables and rice bran, respectively, possess cancer chemopreventive properties in preclinical rodent models. Their pharmacology is only poorly understood. We compared their tissue levels in mice in vivo and their metabolism in liver fractions in vitro. Methods: Mice received apigenin or tricin (0.2%) with their diet for 5-7 days, and flavone levels were compared in the plasma, liver and gastrointestinal mucosa using HPLC-UV. Flavone metabolism was investigated in murine and human liver microsomes or cytosol in vitro co-incubated with uridine 5’-diphosphoglucuronic acid or 3’-phosphoadenosine-5’ phosphosulfate. Flavone metabolites were characterized by on-line HPLC-mass spectrometry. Results: After dietary administration of flavones for 7 days, levels of tricin in plasma, liver and mucosa exceeded those of apigenin by 350, 33 and 100 %, respectively. Apigenin was more rapidly glucuronidated than tricin in liver microsomes, whilst tricin underwent swifter sulfonation than apigenin in liver cytosol. For either flavone the rate of glucuronidation was much faster than that of sulfonation. Flavone monoglucuronides and monosulfates were identified as metabolites in microsomal and cytosolic incubations, respectively. Conclusions: When consumed with the diet in mice tricin seems to be more available than apigenin in blood and tissues. Differences in their glucuronidation may account for their differential availability. Thus tricin may have a pharmacokinetic advantage over apigenin. This type of information may help decide which flavonoids to select for clinical development

Publisher: Springer
Year: 2007
OAI identifier:

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  1. (2001). (eds) Introduction to Drug Metabolism. 3rd Edition,
  2. (1970). (eds). The Systematic Identificantion of Flavonoids.
  3. (2006). A simple HPLC method for the determination of apigenin in mouse tissue. J Biomed Chromatog, doi
  4. (2000). Characterization of potentially chemopreventive phenols in extracts of brown rice which inhibit the growth of human breast and colon cancer cells.
  5. (1998). Column-switching high-performance liquid chromatographic assay for determination of apigenin and acacetin in human urine with ultraviolet absorbance detection. doi
  6. (2003). Determination of the flavone tricin in human plasma by high performance liquid chromatography. doi
  7. (2005). Determination of the putative cancer chemopreventive flavone tricin in plasma and tissue of mice by HPLC with UV-visible detection. doi
  8. (2002). Dietary flavonoids: bioavailability, metabolic effects and safety.
  9. (2006). Differential modulation of cyclooxygenase-mediated prostaglandin production by the putative cancer chemopreventive flavonoids tricin, apigenin and quercetin. Cancer Chemother Pharmacol, doi
  10. (1997). Evaluation of properties of apigenin and [G-3H] apigenin and analytic method development. doi
  11. (2001). Herle AJ
  12. (2002). Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements. doi
  13. (1990). Isolation and studies of the mutagenic activity in the Ames test of flavonoids naturally occurring in medical herbs. doi
  14. (2004). Metabolism of apigenin by rat liver phase I and phase II enzymes and by isolated perfused rat liver. doi
  15. (2004). Pharmacokinetics and metabolism of dietary flavonoids in humans.
  16. (2005). Preliminary safety evaluation of the putative cancer chemopreventive agent tricin, a naturally occurring flavone. doi
  17. (2002). Quercetin glucuronide prevents VSMC hypertrophy by angiotensin H via the inhibition of JNK and AP-1 signaling pathways. doi
  18. (2005). The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMin mice. doi
  19. (1998). United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) Guidelines for the welfare of animals in experimental neoplasia (2nd edition).

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