title: Permeability and conjugative metabolism of flaxseed lignans by Caco-2 human intestinal cells.
abstract: Reports in the literature associate the dietary intake of flaxseed lignans with a number of health benefits. The major lignan found in flaxseed, secoisolariciresinol diglucoside (1), undergoes metabolism principally to secoisolariciresinol (2), enterodiol (3), and enterolactone (4) in the human gastrointestinal tract. Systemically, lignans are present largely as phase II enzyme conjugates. To improve understanding of the oral absorption characteristics, a systematic evaluation of the intestinal permeation was conducted and the conjugative metabolism potential of these lignans using the polarized Caco-2 cell system was analyzed. For permeation studies, lignans (100 μM) were added to acceptor or donor compartments and samples were taken at 2 h. For metabolism studies, lignans (100 μM) were incubated in Caco-2 for a maximum of 48 h. Cell lysates and media were treated with β-glucuronidase/sulfatase, and lignan concentrations were determined using HPLC. Apical-to-basal permeability coefficients for 2-4 were 8.0 ± 0.4, 7.7 ± 0.2, and 13.7 ± 0.2 (×10(-6)) cm/s, respectively, whereas efflux ratios were 0.8-1.2, consistent with passive diffusion. The permeation of compound 1 was not detected. The extent of conjugation after 48 h was <3%, ∼95%, ∼90%, and >99% for 1-4, respectively. These data suggest 2-4, but not 1 undergo passive permeation and conjugative metabolism by Caco-2 cells.
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon, Saskatchewan S7N 5C9, Canada.
authors.forename: Jatinder Kaur
authors.initials: JK
authors.lastname: Mukker
authors.forename: Deborah
authors.initials: D
authors.lastname: Michel
authors.forename: Alister D
authors.initials: AD
authors.lastname: Muir
authors.forename: Ed S
authors.initials: ES
authors.lastname: Krol
authors.forename: Jane
authors.initials: J
authors.lastname: Alcorn
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives; D000465:Algorithms; D002072:Butylene Glycols / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D002851:Chromatography, High Pressure Liquid; D019597:Flax / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D015394:Molecular Structure; D010539:Permeability
chemical_list: D002072:Butylene Glycols; D005960:Glucosides; D017705:Lignans; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; C060283:secoisolariciresinol; D015107:4-Butyrolactone; C090142:secoisolariciresinol diglucoside; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone