title: Intestinal anti-inflammatory effects of total alkaloid extract from Fumaria capreolata in the DNBS model of mice colitis and intestinal epithelial CMT93 cells.
abstract: BACKGROUND
  Fumaria capreolata L. (Papaveraceae) is a botanical drug used in North Africa for its gastro-intestinal and anti-inflammatory properties. It is characterized for the presence of several alkaloids that could be responsible for some of its effects, including an immunomodulatory activity.
  
  
  OBJECTIVE
  To test in vivo the intestinal anti-inflammatory properties of the total alkaloid fraction extracted from the aerial parts of F. capreolata (AFC), and to evaluate its effects on an intestinal epithelial cell line.
  
  
  METHODS
  AFC was chemically characterized by liquid chromatography coupled to diode array detection and high resolution mass spectrometry. Different doses of AFC (25, 50 and 100mg/kg) were assayed in the DNBS model of experimental colitis in mice, and the colonic damage was evaluated both histologically and biochemically. In addition, in vitro experiments were performed with this alkaloid fraction on the mouse intestinal epithelial cell line CMT93 stimulated with LPS.
  
  
  RESULTS
  The chemical analysis of AFC revealed the presence of 23 alkaloids, being the most abundants stylopine, protopine and coptisine. Oral administration of AFC produced a significant inhibition of the release and the expression of IL-6 and TNF-α in the colonic tissue. It also suppressed in vivo the transcription of other pro-inflammatory mediators such as IL-1β, iNOS, IL-12 and IL-17. Furthermore, AFC showed an immunomodulatory effect in vitro since it was able to inhibit the mRNA expression of IL-6, TNF-α and ICAM-1. Moreover, the beneficial effect of AFC in the colitic mice could also be associated with the normalization of the expression of MUC-2 and ZO-1, which are important for the intestinal epithelial integrity.
  
  
  CONCLUSIONS
  The present study suggests that AFC, containing 1.3% of stylopine and 0.9% of protopine, significantly exerted intestinal anti-inflammatory effects in an experimental model of mouse colitis. This fact could be related to a modulation of the intestinal immune response and a restoration of the intestinal epithelial function.
authors.affiliation: Laboratoire de Biotechnologies Végétales et Ethnobotanique, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000 Bejaia, Algeria; CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain.
authors.forename: Noureddine
authors.initials: N
authors.lastname: Bribi
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain.
authors.forename: Francesca
authors.initials: F
authors.lastname: Algieri
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Rodriguez-Nogales
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Vezza
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Garrido-Mesa
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain.
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Utrilla
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avenida Fuentenueva s/n, 18071-Granada, Spain; Research and Development Centre for Functional Food (CIDAF), Health-Science Technological Park, Avenida del Conocimiento 37, 18016-Granada, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Del Mar Contreras
authors.affiliation: Laboratoire de Biotechnologies Végétales et Ethnobotanique, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000 Bejaia, Algeria.
authors.forename: Fadila
authors.initials: F
authors.lastname: Maiza
authors.affiliation: Department of Analytical Chemistry, Faculty of Sciences, University of Granada, Avenida Fuentenueva s/n, 18071-Granada, Spain; Research and Development Centre for Functional Food (CIDAF), Health-Science Technological Park, Avenida del Conocimiento 37, 18016-Granada, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Segura-Carretero
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Rodriguez-Cabezas
authors.affiliation: CIBER-EHD, Department of Pharmacology, ibs.GRANADA, Center for Biomedical Research (CIBM), University of Granada, Avenida del Conocimiento s/n 18016-Armilla, Granada, Spain. Electronic address: jgalvez@ugr.es.
authors.forename: Julio
authors.initials: J
authors.lastname: Gálvez
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D016207:Cytokines / Q000037:antagonists & inhibitors; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives; D004847:Epithelial Cells / Q000187:drug effects; D031312:Fumaria / Q000737:chemistry*; D007155:Immunologic Factors / Q000494:pharmacology; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004139:Dinitrofluorobenzene; D007155:Immunologic Factors; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C045305:2,4-dinitrofluorobenzene sulfonic acid
keywords: Cytokine, Stylopine; DNBS mouse colitis; Fumaria capreolata; Intestinal inflammation; protopine