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Cited by 29Plant-derived Lignans Synthesis and BioactivityLignin and Wood ChemistryDrug Solubulity and Delivery Systems

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Permeability and Conjugative Metabolism of Flaxseed Lignans by Caco-2 Human Intestinal Cells

Mukker, Jatinder Kaur, Michel, Deborah, Muir, Alister D., Krol, Ed S., Alcorn, Jane·2014·Journal of Natural Products
DOI 10.1021/np4004905
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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.

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Cited by

Metadata

Authors
Mukker, J. K., Michel, D., Muir, A. D., Krol, E. S., & Alcorn, J.
Affiliations
  • University of Saskatchewan (CA)
  • Agriculture and Agri-Food Canada (CA)
Corresponding author
Alcorn, Jane
ORCID
Venue
Journal of Natural Products
Publisher
American Chemical Society (ACS)
Published
2014-01-13
Volume
77
Issue
1
Pages
29-34
ISSN
  • 0163-3864 (ISSN-L)
  • 1520-6025
DOI
10.1021/np4004905
OpenAlex
W2332306248
Cited by
29
References
0
Citations by year
2026: 1 · 2024: 2 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 2
FWCI
1.37
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Natural Products (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant-derived Lignans Synthesis and Bioactivity
  • Physical Sciences › Chemical Engineering › Process Chemistry and Technology › Lignin and Wood Chemistry
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
Keywords
flaxseed lignans, secoisolariciresinol diglucoside, secoisolariciresinol, enterodiol, enterolactone, intestinal permeability, passive diffusion, efflux ratio, phase II conjugation, glucuronidation, sulfation, Caco-2 cells, dietary lignans, gastrointestinal metabolism
MeSH terms
Algorithms, Butylene Glycols, Chromatography, High Pressure Liquid, Glucosides, Humans, Intestinal Mucosa, Permeability, 4-Butyrolactone, Molecular Structure, Lignans, Caco-2 Cells, Flax

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