title: Intestinal anti-inflammatory activity of hydroalcoholic extracts of Phlomis purpurea L. and Phlomis lychnitis L. in the trinitrobenzenesulphonic acid model of rat colitis.
abstract: BACKGROUND
  Different species from genus Phlomis, frequently native from the the eastern Mediterranean zone, have been used in traditional medicine as an anti-inflammatory remedy. Among other constituents, they contain polyphenols that show antioxidant properties, which are interesting for the treatment of inflammatory pathologies associated with oxidative stress in humans, such as inflammatory bowel disease (IBD). The aim of this study was to evaluate the intestinal anti-inflammatoy effect of hydroalcoholic extracts of Phlomis lychnitis and P. purpurea in the trinitrobenzenesulphonic acid (TNBS) model of rat colitis, a well characterized experimental model with some resemblance to human IBD.
  
  
  METHODS
  Hydroalcoholic extracts of both plants were characterized by determining their polyphenolic content and then assayed in the TNBS model of rat colitis. For this purpose, female Wistar rats were assigned to seven groups (n=10): healthy control, untreated TNBS-colitis and five TNBS- colitis groups treated with Phlomis lychnitis (10 and 20mg/kg), P. purpurea (10 and 25mg/kg) and sulphasalazine (200mg/kg), as a positive control. Treatments started the same day of TNBS colitis induction, and rats were sacrificed one week later. Colonic inflammation was evaluated both histologically and biochemically.
  
  
  RESULTS
  The histological (macroscopic and microscopic) analysis of colonic samples revealed that both extracts showed an anti-inflammatory effect, which was confirmed biochemically by a decreased colonic MPO activity, a maker of neutrophil infiltration, an increased colonic glutathione content, which counteracts the oxidative status associated with the inflammatory process, and a down-regulated iNOS expression. However, only the extract of P. purpurea reduced the expression of the proinflammatory cytokines IL-1β and IL-17, the chemokines CINC-1 and MCP-1, as well as the adhesion molecule ICAM-1, ameliorating the altered immune response associated with the colonic inflammation. Furthermore, both P. lychnitis and P. purpurea extracts were able to significantly increase the expression of markers of epithelial integrity such as MUC-2, MUC-3 and villin, thus revealing an improvement in the altered colonic permeability that characterizes colonic inflammation.
  
  
  CONCLUSIONS
  Both extracts showed intestinal anti-inflammatory activity in the TNBS model of rat colitis, thus confirming their traditional use in digestive inflammatory complaints. In addition to their antioxidant properties, other mechanisms can contribute to this beneficial effect, like an improvement in the intestine epithelial barrier and a downregulation of the immune response.
authors: CIBER-EHD, Department of Pharmacology, Center for Biomedical Research, University of Granada, Granada, Spain.
authors: Francesca
authors: F
authors: Algieri
authors: Pedro
authors: P
authors: Zorrilla
authors: Alba
authors: A
authors: Rodriguez-Nogales
authors: Natividad
authors: N
authors: Garrido-Mesa
authors: Oscar
authors: O
authors: Bañuelos
authors: M Reyes
authors: MR
authors: González-Tejero
authors: Manuel
authors: M
authors: Casares-Porcel
authors: Joaquín
authors: J
authors: Molero-Mesa
authors: Antonio
authors: A
authors: Zarzuelo
authors: M Pilar
authors: MP
authors: Utrilla
authors: M Elena
authors: ME
authors: Rodriguez-Cabezas
authors: Julio
authors: J
authors: Galvez
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009077:Mucins / Q000378:metabolism; D009336:Necrosis; D009195:Peroxidase / Q000378:metabolism; D031345:Phlomis / Q000737:chemistry*; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D009077:Mucins; D010936:Plant Extracts; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D005978:Glutathione