RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Xinqin, a polyherbal medicine, is an important traditional Chinese herbal formula used in traditional oriental medicine for treatment of allergic rhinitis (AR). The formula is based on the Chinese Pharmacopoeia AIM OF THE STUDY: Previously, Xinqin exhibited potent anti-allergic effect in a guinea pig model of AR. In this study, we explored the molecular mechanism of the anti-allergic effect mediated by Xinqin. MATERIALS AND METHODS: AR was induced in guinea pigs (Hartley) with toluene-2, 4-diisocyanate (TDI) in vivo and in HMC-1 mast cells with A23187/phorbol 12-myristate-13-acetate (PMA) in vitro. The releases of allergic inflammatory mediators such as histamine, leukotriene (LT) D4, immunoglobulin (Ig) E, TNF-α, and IL-6 were analyzed for allergy. The mast cell degranulation was displayed in HMC-1 mast cells. The activities of janus protein kinase 2 (JAK2), signal transduction and activator of transcription 5 (STAT5) and suppressor of cytokine signaling 3 (SOCS3) were evaluated by Western blot. RESULTS: Treatment with Xinqin resulted in AR symptoms and decreases in levels of histamine, LTD4, IgE, TNF-α, and IL-6 in serum of guinea pig model of AR and in A23187/PMA-stimulated HMC-1 mast cells. Treatment with Xinqin also inhibited cell degranulation in A23187/PMA-stimulated HMC-1 mast cells. The JAK2/STAT5 signaling pathway could play an important role in the anti-allergic activity mediated by Xinqin. CONCLUSIONS: Xinqin exerts the anti-allergic effect by modulating mast cell-mediated allergic responses by down-regulating JAK2/STAT5 signaling pathway. Results from this study provide a mechanistic basis for the application of Xinqin in the treatment of AR.
Assuntos
Antialérgicos/farmacologia , Degranulação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Janus Quinase 2/metabolismo , Mastócitos/efeitos dos fármacos , Rinite Alérgica/tratamento farmacológico , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Calcimicina/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Cobaias , Histamina/sangue , Humanos , Imunoglobulina E/sangue , Interleucina-6/sangue , Leucotrieno D4/sangue , Masculino , Mastócitos/enzimologia , Fosforilação , Rinite Alérgica/sangue , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/enzimologia , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Tolueno 2,4-Di-Isocianato , Fator de Necrose Tumoral alfa/sangueRESUMO
Three inhalation formulations of ICI 204,219 were compared for antagonism of antigen-induced bronchoconstriction in 16 subjects with asthma who demonstrated reproducible hypersensitivity to allergen during screening challenges. Each subject received a single 0.2-mg dose of each formulation and was challenged with ragweed 30 min after administration of ICI 204,219 until the forced expiratory volume in 1 s (FEV1) decreased by 20 percent or the maximum allergen concentration (100 micrograms/ml) was reached. The majority of subjects tolerated 100 micrograms/ml of allergen without a 20 percent decrease in FEV1. Inhalation formulations of ICI 204,219 successfully inhibited bronchoconstriction in subjects with reproducible sensitivity to ragweed challenges.