title: Apigenin supplementation protects the development of dextran sulfate sodium-induced murine experimental colitis by inhibiting canonical and non-canonical inflammasome signaling pathways.
abstract: The present study was designed to elucidate the protective effects of dietary apigenin (API) enrichment in a chronic colitis model induced by DSS in mice. Inflammatory mediators and the possible role of canonical and non-canonical NLRP3 inflammasome signaling pathways in the beneficial effects of API under chronic inflammatory conditions were also explored. Six-week-old mice were randomized in four dietary groups: sham and control groups received standard diet (SD), and other two groups were fed with API at 0.1%. After 30days, all groups except sham received 3% DSS in drinking water for 5days followed by a regime of 21days of water. Our results revealed that dietary API supplementation decreased the macroscopic and microscopic damage signs of colitis; also, it was capable to down-regulate mPGES, COX-2 and iNOS enzyme colonic expressions and to decrease serum matrix metalloproteinase (MMP-3) levels. Similarly, API diet reduced IL-1β and TNF-α proinflammatory cytokine secretions in primary LPS-stimulated splenocytes. Furthermore, we demonstrated that API anti-inflammatory activity was related with an inhibition of both canonical and non-canonical NLRP3 inflammasome pathways by decreasing proinflammatory IL-1β and IL-18 cytokine levels as a consequence of regulation of cleaved caspase-1 and caspase-11 enzymes. We conclude that API supplement might provide a basis for developing a new dietary strategy for the prevention of chronic ulcerative colitis.
authors.affiliation: Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Campus Zacatenco, Instituto Politécnico Nacional, Av. Wilfrido Massieu s/n Col. Zacatenco, CP 07730, Mexico, DF, Mexico; Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, 41012, Seville, Spain. Electronic address: ymarquez@ipn.mx.
authors.forename: Yazmín K
authors.initials: YK
authors.lastname: Márquez-Flores
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, 41012, Seville, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Villegas
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, 41012, Seville, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cárdeno
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, 41012, Seville, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Rosillo
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, 41012, Seville, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Alarcón-de-la-Lastra
mesh_terms: D000818:Animals; D047310:Apigenin / Q000008:administration & dosage*; D003092:Colitis / Q000139:chemically induced*; D016264:Dextran Sulfate / Q000009:adverse effects*; D005260:Female; D058847:Inflammasomes / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction
chemical_list: D058847:Inflammasomes; D047310:Apigenin; D016264:Dextran Sulfate
keywords: Apigenin; DSS; caspases; chronic colitis; inflammasome