Absorption and metabolism of flavonoids in the caco-2 cell culture model and a perused rat intestinal model.

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  • Author(s): Liu Y;Liu Y; Hu M
  • Source:
    Drug metabolism and disposition: the biological fate of chemicals [Drug Metab Dispos] 2002 Apr; Vol. 30 (4), pp. 370-7.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Society for Pharmacology and Experimental Therapeutics, etc.] Country of Publication: United States NLM ID: 9421550 Publication Model: Print Cited Medium: Print ISSN: 0090-9556 (Print) Linking ISSN: 00909556 NLM ISO Abbreviation: Drug Metab Dispos Subsets: MEDLINE
    • Publication Information:
      Original Publication: [Bethesda, Md., etc., American Society for Pharmacology and Experimental Therapeutics, etc.]
    • Subject Terms:
      Anticarcinogenic Agents/*metabolism ; Caco-2 Cells/*metabolism ; Flavonoids/*metabolism ; Intestinal Absorption/*physiology ; Intestinal Mucosa/*metabolism; Animals ; Apigenin ; Biological Transport/physiology ; Caco-2 Cells/cytology ; Catheterization ; Cell Line ; Genistein/analogs & derivatives ; Genistein/metabolism ; Humans ; Hydrolysis ; Isoflavones/metabolism ; Male ; Models, Biological ; Perfusion ; Rats ; Rats, Sprague-Dawley ; beta-Glucosidase/metabolism
    • Abstract:
      The purpose of present study was to determine the intestinal absorption and metabolism of genistein and its analogs to better understand the mechanisms responsible for their low oral bioavailability. The Caco-2 cell culture model and a perfused rat intestinal model were used for the study. In both models, permeabilities of aglycones (e.g., genistein) were comparable to well absorbed compounds, such as testosterone and propranolol. In the Caco-2 model, permeabilities of aglycones were at least 5 times higher (p < 0.05) than their corresponding glycosides (e.g., genistin), and the vectorial transport of aglycones was similar (p > 0.05). In contrast, vectorial transport of glucosides favored excretion (p < 0.05). Limited hydrolysis of glycosides was observed in the Caco-2 model, which was completely inhibited (p < 0.05) by 20 mM gluconolactone, a broad specificity glycosidase inhibitor. In the perfused rat intestinal model, genistin was rapidly hydrolyzed (about 40% in 15 min) in the upper intestine but was not hydrolyzed at all in the colon. Aglycones were rapidly absorbed (P*(eff) > 1.5), and absorbed aglycones underwent extensive (40% maximum) phase II metabolism via glucuronidation and sulfation in the upper small intestine. Similar to the hydrolysis, recovery of conjugated genistein was also region-dependent, with jejunum having the highest and colon the lowest (p < 0.05). This difference in conjugate recovery could be due to the difference in the activities of enzymes or efflux transporters, and the results of studies tend to suggest that both of these factors were involved. In conclusion, genistein and its analogs are well absorbed in both intestinal models, and therefore, poor absorption is not the reason for its low bioavailability. On the other hand, extensive phase II metabolism in the intestine significantly contributes to its low bioavailability.
    • Grant Information:
      AT00182 United States AT NCCIH NIH HHS; GM52270 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (Anticarcinogenic Agents)
      0 (Flavonoids)
      0 (Isoflavones)
      1POG3SCN5T (genistin)
      7OF2S66PCH (apigetrin)
      7V515PI7F6 (Apigenin)
      DH2M523P0H (Genistein)
      EC 3.2.1.21 (beta-Glucosidase)
    • Publication Date:
      Date Created: 20020320 Date Completed: 20020517 Latest Revision: 20190607
    • Publication Date:
      20240829
    • Accession Number:
      10.1124/dmd.30.4.370
    • Accession Number:
      11901089