title: Luteolin suppresses the JAK/STAT pathway in a cellular model of intestinal inflammation.
abstract: Current treatment strategies for inflammatory bowel diseases (IBDs) are associated with a lower efficacy and with several side effects that strongly affect the quality of life of IBD patients. Consequently, the development of new therapies, combining efficacy and safety is an important goal in the field of intestinal inflammation. In this context, evidence supports that polyphenols can be promising candidates due to their ability to modulate intracellular inflammatory signalling cascades. Luteolin, a naturally occurring flavonoid, exhibits anti-inflammatory properties in several models of inflammation. However, its action against intestinal inflammation has been poorly explored. Therefore, there is a lack of scientific knowledge about the potential impact of luteolin in the intestinal inflammation, particularly regarding the underlying molecular mechanisms by which luteolin can exert its anti-inflammatory action. We assessed the potential anti-inflammatory effect of luteolin in a cellular model of intestinal inflammation using cytokine-stimulated HT-29 colon epithelial cells, and the underlying key molecular mechanisms were identified. Luteolin significantly inhibited interleukine-8 (IL-8) production, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression and nitric oxide (˙NO) overproduction induced by cytokines, indicating that luteolin negatively modulates key inflammatory signalling cascades underlying intestinal inflammation. Mechanistically, the inhibition of the JAK/STAT pathway was identified as a critical mechanism by which luteolin exerts its intestinal anti-inflammatory action. This study uncovers novel molecular mechanisms by which luteolin may act against intestinal inflammation, which might support the use of luteolin as a future therapeutic strategy in IBD.
authors.affiliation: Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal. carlapumky@gmail.com.
authors.forename: Carla
authors.identifier: http://orcid.org/0000-0002-7452-1592
authors.initials: C
authors.lastname: Nunes
authors.affiliation: Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal. carlapumky@gmail.com.
authors.forename: Leonor
authors.initials: L
authors.lastname: Almeida
authors.affiliation: Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal. carlapumky@gmail.com.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Barbosa
authors.affiliation: Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal. carlapumky@gmail.com.
authors.forename: João
authors.initials: J
authors.lastname: Laranjinha
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000187:drug effects* / Q000276:immunology*; D053613:Janus Kinase 1 / Q000235:genetics / Q000276:immunology*; D047311:Luteolin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D050791:STAT Transcription Factors; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D053613:Janus Kinase 1; D047311:Luteolin