title: Curine inhibits eosinophil activation and airway hyper-responsiveness in a mouse model of allergic asthma.
abstract: Allergic asthma is a chronic inflammatory airway disease with increasing prevalence around the world. Current asthma therapy includes drugs that usually cause significant side effects, justifying the search for new anti-asthmatic drugs. Curine is a bisbenzylisoquinoline alkaloid that modulates calcium influx in many cell types; however, its anti-allergic and putative toxic effects remain to be elucidated. Our aim was to investigate the effects of curine on eosinophil activation and airway hyper-responsiveness (AHR) and to characterize its potential toxic effects. We used a mouse model of allergic asthma induced by sensitization and challenge with ovalbumin (OVA) to evaluate the anti-allergic effects of oral treatment with curine. The oral administration of curine significantly inhibited eosinophilic inflammation, eosinophil lipid body formation and AHR in animals challenged with OVA compared with animals in the untreated group. The curine treatment also reduced eotaxin and IL-13 production triggered by OVA. Verapamil, a calcium channel antagonist, had similar anti-allergic properties, and curine pre-treatment inhibited the calcium-induced tracheal contractile response ex-vivo, suggesting that the mechanism by which curine exerts its effects is through the inhibition of a calcium-dependent response. A toxicological evaluation showed that orally administered curine did not significantly alter the biochemical, hematological, behavioral and physical parameters measured in the experimental animals compared with saline-treated animals. In conclusion, curine showed anti-allergic activity through mechanisms that involve inhibition of IL-13 and eotaxin and of Ca(++) influx, without inducing evident toxicity and as such, has the potential for the development of anti-asthmatic drugs.
authors.affiliation: Laboratório de Imunofarmacologia, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil; Laboratório de Imunofarmacologia, Departamento de Fisiologia e Patologia, UFPB, João Pessoa, Paraíba, Brazil.
authors.forename: Jaime
authors.initials: J
authors.lastname: Ribeiro-Filho
authors.forename: Andrea Surrage
authors.initials: AS
authors.lastname: Calheiros
authors.forename: Adriana
authors.initials: A
authors.lastname: Vieira-de-Abreu
authors.forename: Katharinne Ingrid Moraes
authors.initials: KI
authors.lastname: de Carvalho
authors.forename: Diego
authors.initials: D
authors.lastname: da Silva Mendes
authors.forename: Christianne Bandeira
authors.initials: CB
authors.lastname: Melo
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Martins
authors.forename: Celidarque
authors.initials: C
authors.lastname: da Silva Dias
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: Piuvezam
authors.forename: Patrícia T
authors.initials: PT
authors.lastname: Bozza
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000633:toxicity*; D001249:Asthma / Q000188:drug therapy*; D016535:Bronchial Hyperreactivity / Q000188:drug therapy; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D018793:Interleukin-13 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007546:Isoquinolines / Q000633:toxicity*; D008297:Male; D029583:Menispermaceae / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D019055:No-Observed-Adverse-Effect Level; D010047:Ovalbumin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018927:Anti-Asthmatic Agents; D018793:Interleukin-13; D007546:Isoquinolines; C470478:curine; D010047:Ovalbumin; D014700:Verapamil; D002118:Calcium
keywords: Airway hyper-responsiveness; Allergy; Calcium; Curine; Eosinophil activation; Toxicity