title: Curine inhibits mast cell-dependent responses in mice.
abstract: BACKGROUND
  Curine is a bisbenzylisoquinoline alkaloid and the major constituent isolated from Chondrodendron platyphyllum, a plant that is used to treat inflammatory diseases in Brazilian folk medicine. This study investigates the effectiveness of curine on mast cell-dependent responses in mice.
  
  
  METHODS
  To induce mast cell-dependent responses, Swiss mice were subcutaneously sensitized with ovalbumin (OVA-12 μg/mouse) and Al(OH)3 in a 0.9% NaCl solution. Fifteen days later, the animals were challenged with OVA through different pathways. Alternatively, the animals were injected with compound 48/80 or histamine, and several parameters, including anaphylaxis, itching, edema and inflammatory mediator production, were analyzed. Promethazine, cromoglycate, and verapamil were used as control drugs, and all of the treatments were performed 1h before the challenges.
  
  
  RESULTS
  Curine pre-treatment significantly inhibited the scratching behavior and the paw edema induced by either compound 48/80 or OVA, and this protective effect was comparable in magnitude with those associated with treatment with either cromoglycate or verapamil. In contrast, curine was a weak inhibitor of histamine-induced paw edema, which was completely inhibited by promethazine. Curine and verapamil significantly inhibited pleural protein extravasations and prostaglandin D2 (PGD2) and cysteinyl leukotrienes (CysLTs) production following allergen-induced pleurisy. Furthermore, like verapamil, curine inhibited the anaphylactic shock caused by either compound 48/80 or an allergen. In in vitro settings, these treatments also inhibited degranulation as well as PGD2 and CysLT production through IgE-dependent activation of the mast cell lineage RBL-2H3.
  
  
  CONCLUSIONS
  Curine significantly inhibited immediate allergic reactions through mechanisms more related to mast cell stabilization and activation inhibition than interference with the pro-inflammatory effects of mast cell products. These findings are in line with the hypothesis that the alkaloid curine may be beneficial for the treatment of allergic disorders.
authors: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, RJ, Brazil.
authors: Jaime
authors: J
authors: Ribeiro-Filho
authors: Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba, Brazil.
authors: Fagner Carvalho
authors: FC
authors: Leite
authors: Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba, Brazil.
authors: Hermann Ferreira
authors: HF
authors: Costa
authors: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, RJ, Brazil.
authors: Andrea Surrage
authors: AS
authors: Calheiros
authors: Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors: Rafael Carvalho
authors: RC
authors: Torres
authors: Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors: Carolina Trindade
authors: CT
authors: de Azevedo
authors: Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
authors: Marco Aurélio
authors: MA
authors: Martins
authors: Laboratório de Fitoquímica, Departamento de Ciências Farmacêuticas, UFPB, João Pessoa, Paraíba, Brazil.
authors: Celidarque da Silva
authors: Cda S
authors: Dias
authors: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, 21040-360 Rio de Janeiro, RJ, Brazil. Electronic address: pbozza@ioc.fiocruz.br.
authors: Patrícia T
authors: PT
authors: Bozza
authors: Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba, Brazil.
authors: Márcia Regina
authors: MR
authors: Piuvezam
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000302:isolation & purification / Q000494:pharmacology; D001938:Brazil; D004195:Disease Models, Animal; D006632:Histamine / Q000276:immunology; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D006969:Hypersensitivity, Immediate / Q000188:drug therapy / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007546:Isoquinolines / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D008519:Medicine, Traditional; D029583:Menispermaceae / Q000737:chemistry*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000485:Allergens; D018926:Anti-Allergic Agents; D007546:Isoquinolines; D007073:Immunoglobulin E; C470478:curine; D006632:Histamine; D010047:Ovalbumin
keywords: Anti-allergic; Chondrodentron platyphyllum; Curine; Lipid mediators; Mast cell