Análise celular e molecular do efeito da instilação nasal do extrato das folhas de Cissampelos sympodialis Eichl (Menispermaceae) e seus alcaloides no processo alérgico experimental

• Ano de defesa: 2014
• Autor(a) principal: Vieira, Giciane Carvalho
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal da Paraí­ba; BR; Farmacologia; Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos; UFPB
• Palavras-chave em Português: Cissampelos sympodialis; Asma; Warifteína; Metilwarifteína; Milonina; Instilação nasal; Asthma; Warifteine; Intranasally; CIENCIAS BIOLOGICAS::FARMACOLOGIA
• Link de acesso: https://repositorio.ufpb.br/jspui/handle/tede/6811

Cissampelos sympodialis Eichl (Menispermaceae) is a plant commonly found in semi-arid regions of Brazil. Its roots and leaves are used in folk medicine to treat arthritis, rheumatism and respiratory disorders. Studies have shown its anti-inflammatory, immunomodulatory and anti-asthmatic effects. The aim of this study was: 1) to evaluate the effect of administration, intranasally (i.n.) of the leave extract (AFL) and its alkaloids warifteine (WAR), methylwarifteine (MWA) and milonine (MIL) in the lungs of BALB/c mice sensitized and challenged with ovalbumin (OVA) and 2) to analyze the effects of alkaloids on inflammatory cells and their molecules related to inflammation. The parameters evaluated in vivo were: the cell migration into bronchoalveolar lavage (BAL), histopathological changes in the lung tissue and analysis of IgE levels on the serum. In vitro assays, were evaluated the phosphorylation of JNK kinase enzyme and expression of COX-2 on cultured macrophage and mast cells. The results showed that the AFL and the alkaloids were able to inhibit the migration of inflammatory cells, mainly eosinophils to the lung. However the AFL and milonine induced neutrophil migration to the lung. Treatment with the extract and the alkaloids inhibited the production of mucus by goblet cells present in the bronchial epithelium and the migration of TCD4+ and TCD8+ into the lung tissue, except warfteine that increased the TCD8+ subpopulation,. Only the AFL treatment was able to decrease serum IgE concentration and, among the alkaloids, MWA was able to inhibit the production of interleukin-13 (IL-13) by cells from the BAL. In vitro tests showed that the alkaloids presented no toxicity for macrophage and mast cells at all concentrations tested 0.1, 1.0 and 10 μM. However, only milonine was able to inhibit degranulation of mast cells via inhibition of histamine release. The inhibition of JNK phosphorylation was observed with MWA and MIL independent of COX-2 activation. These results indicate that the extract, when administered intranasally, has antiasthmatic effect by decreasing the eosinophil migration into the lung and the mucus production and, MWA is one of the important compounds present into the extract due to decreasing the JNK phosphorylation. In addition, these data provide additional information to produce an herbal plant for the treatment of intranasal airway inflammatory disorders and the MWA may be the molecular marker for the quality and effect of the herbal medicine.