title: Among plant lignans, pinoresinol has the strongest antiinflammatory properties in human intestinal Caco-2 cells.
abstract: Dietary lignans show some promising health benefits, but little is known about their fate and activities in the small intestine. The purpose of this study was thus to investigate whether plant lignans are taken up by intestinal cells and modulate the intestinal inflammatory response using the Caco-2 cell model. Six lignan standards [secoisolariciresinol diglucoside (SDG), secoisolariciresinol (SECO), pinoresinol (PINO), lariciresinol, matairesinol (MAT), and hydroxymatairesinol] and their colonic metabolites [enterolactone (ENL) and enterodiol] were studied. First, differentiated cells were exposed to SDG, SECO, PINO, or ENL at increasing concentrations for 4 h, and their cellular contents (before and after deconjugation) were determined by HPLC. Second, in IL-1β-stimulated confluent and/or differentiated cells, lignan effects were tested on different soluble proinflammatory mediators quantified by enzyme immunoassays and on the NF-κB activation pathway by using cells transiently transfected. SECO, PINO, and ENL, but not SDG, were taken up and partly conjugated by cells, which is a saturable conjugation process. PINO was the most efficiently conjugated (75% of total in cells). In inflamed cells, PINO significantly reduced IL-6 by 65% and 30% in confluent and differentiated cells, respectively, and cyclooxygenase (COX)-2-derived prostaglandin E(2) by 62% in confluent cells. In contrast, MAT increased significantly COX-2-derived prostaglandin E(2) in confluent cells. Moreover, PINO dose-dependently decreased IL-6 and macrophage chemoattractant protein-1 secretions and NF-κB activity. Our findings suggest that plant lignans can be absorbed and metabolized in the small intestine and, among the plant lignans tested, PINO exhibited the strongest antiinflammatory properties by acting on the NF-κB signaling pathway, possibly in relation to its furofuran structure and/or its intestinal metabolism.
authors.affiliation: Institut des Sciences de la Vie, Université Catholique de Louvain, Louvain-la-Neuve, Belgium. alexandrine.during@univ-lille2.fr
authors.forename: Alexandrine
authors.initials: A
authors.lastname: During
authors.forename: Céline
authors.initials: C
authors.lastname: Debouche
authors.forename: Thomas
authors.initials: T
authors.lastname: Raas
authors.forename: Yvan
authors.initials: Y
authors.lastname: Larondelle
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002072:Butylene Glycols / Q000494:pharmacology; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005663:Furans / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000187:drug effects* / Q000473:pathology; D017705:Lignans / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D002072:Butylene Glycols; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D005663:Furans; D005960:Glucosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D017705:Lignans; D016328:NF-kappa B; D010936:Plant Extracts; C419306:hydroxymatairesinol; C068935:matairesinol; C060282:lariciresinol; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C060283:secoisolariciresinol; D015107:4-Butyrolactone; C090142:secoisolariciresinol diglucoside; C103298:pinoresinol; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone