Exceptionally fast uptake and metabolism of cyanidin 3-glucoside by rat kidneys and liver.

To asses the hypothesis that anthocyanins are rapidly taken up from the blood into tissues, where they accumulate up to their bioactivity threshold, an intravenous dose of cyanidin 3-glucoside (1) was administered to anaesthetized rats. Cyanidin 3-glucoside (1) and its metabolites were analyzed in the plasma, kidneys, liver, urine, and bile, using last-generation mass spectrometry. Compound 1 was found to rapidly disappear from plasma (t/2=0.36 min). As soon as 15 s after its administration, both 1 and its methylation product, peonidin 3-glucoside (2), were detected in the plasma, kidneys, and liver. At 1 min, both 1 and 2 had almost disappeared from the plasma, but attained their peak concentrations in the kidneys and in the liver. Compound 2 was rapidly excreted both in the bile and in the urine. Three additional methylated metabolites were detected in traces, namely, delphinidin 3-glucoside (3), petunidin 3-glucoside (4), and malvidin 3-glucoside (5). These data contribute to solving the paradox of the high bioactivity of anthocyanins in spite of their apparent low bioavailability.

[1]  G. Forni,et al.  Studies on Vaccinium myrtillus anthocyanosides. II. Aspects of anthocyanins pharmacokinetics in the rat. , 1976, Arzneimittel-Forschung.

[2]  P. Morazzoni,et al.  Vaccinium myrtillus anthocyanosides pharmacokinetics in rats. , 1991, Arzneimittel-Forschung.

[3]  M. Saier.  A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters , 2000, Microbiology and Molecular Biology Reviews.

[4]  F. Lombardo,et al.  Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. , 2001, Advanced drug delivery reviews.

[5]  F. Mattivi,et al.  The interaction of anthocyanins with bilitranslocase. , 2002, Biochemical and biophysical research communications.

[6]  B. Zhu.  Catechol-O-Methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: importance in pathophysiology and pathogenesis. , 2002, Current drug metabolism.

[7]  F. Mattivi,et al.  The stomach as a site for anthocyanins absorption from food 1 , 2003, FEBS letters.

[8]  F. Mattivi,et al.  Fast access of some grape pigments to the brain. , 2005, Journal of agricultural and food chemistry.

[9]  M. Hirayama,et al.  Metabolic Pathway of Cyanidin 3-O-β-d-Glucopyranoside in Rats , 2005 .

[10]  J. Haywood,et al.  Harmonization of Animal Care and Use Guidance , 2006, Science.

[11]  G. Beecher,et al.  Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. , 2006, Journal of agricultural and food chemistry.

[12]  M. Hirayama,et al.  Ingested delphinidin-3-rutinoside is primarily excreted to urine as the intact form and to bile as the methylated form in rats. , 2006, Journal of agricultural and food chemistry.

[13]  H. Ohguro,et al.  Comparative assessment of distribution of blackcurrant anthocyanins in rabbit and rat ocular tissues. , 2006, Experimental eye research.

[14]  C. Akoh,et al.  Absorption of anthocyanins from blueberry extracts by caco-2 human intestinal cell monolayers. , 2006, Journal of agricultural and food chemistry.

[15]  R. Prior,et al.  Anthocyanins: Structural characteristics that result in unique metabolic patterns and biological activities , 2006, Free radical research.

[16]  D. Bagchi,et al.  Berry anthocyanins as novel antioxidants in human health and disease prevention. , 2007, Molecular nutrition & food research.

[17]  H. Ashida,et al.  Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. , 2007, Biochemical pharmacology.

[18]  T. McGhie,et al.  The bioavailability and absorption of anthocyanins: towards a better understanding. , 2007, Molecular nutrition & food research.

[19]  R. Steinert,et al.  Absorption of black currant anthocyanins by monolayers of human intestinal epithelial Caco-2 cells mounted in ussing type chambers. , 2008, Journal of agricultural and food chemistry.

[20]  G. Stoner,et al.  Anthocyanins and their role in cancer prevention. , 2008, Cancer letters.

[21]  S. Passamonti,et al.  Bioavailability of flavonoids: a review of their membrane transport and the function of bilitranslocase in animal and plant organisms. , 2009, Current drug metabolism.

[22]  B. Shukitt-Hale,et al.  Recent advances in berry supplementation and age-related cognitive decline , 2009, Current opinion in clinical nutrition and metabolic care.

[23]  K. Brown,et al.  Pharmacokinetics and metabolism of the putative cancer chemopreventive agent cyanidin-3-glucoside in mice , 2009, Cancer Chemotherapy and Pharmacology.

[24]  Y. Hao,et al.  Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects. , 2009, The American journal of clinical nutrition.

[25]  S. Passamonti,et al.  Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter. , 2010, Cardiovascular research.