RESUMO
This study aimed to determine whether brazilin exhibits anti-inflammatory effects that inhibit T helper cell type II (T(H)2) responses and whether it suppresses allergic inflammation reactions in a murine model of asthma. We found that brazilin inhibited the mRNA and protein expression of interleukin (IL)-4 and IL-5 induced by phorbol myristate acetate (PMA) and cAMP in EL-4 T cells in a dose-dependent manner. Following the intratracheal instillation of brazilin in ovalbumin (OVA)-immunized mice, we found that brazilin-treated mice exhibited decreases in the release of IL-4, IL-5, IL-13, eotaxin-1, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF); inhibited T(H)2 functioning via a decrease in IL-4 production; and exhibited attenuation of OVA-induced lung eosinophilia, airway hyperresponsiveness, and airway remodeling. These results suggest that brazilin exhibits anti-T(H)2 effects both in vitro and in vivo and may possess therapeutic potential for allergic diseases.
Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Benzopiranos/uso terapêutico , Células Th2/imunologia , Animais , Antiasmáticos/farmacologia , Benzopiranos/farmacologia , Líquido da Lavagem Broncoalveolar/imunologia , Quimiocina CCL11/análise , Modelos Animais de Doenças , Feminino , Interleucina-13/análise , Interleucina-4/análise , Interleucina-4/antagonistas & inibidores , Interleucina-4/genética , Interleucina-5/análise , Interleucina-5/antagonistas & inibidores , Interleucina-5/genética , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Células Th2/efeitos dos fármacos , Fator de Necrose Tumoral alfa/análiseRESUMO
The vasorelaxant activity of Caesalpinia sappan L., a traditional Chinese medicine, and its major component brazilin were investigated in isolated rat aorta and human umbilical vein endothelial cells. In isolated rat aorta, C. sappan L. extract and brazilin relaxed phenylephrine-induced vasocontraction and increased cyclic guanosine 3',5'-monophosphate (cGMP) content. Induction of vasorelaxation of brazilin was endothelium-dependent and could be markedly blocked by pretreatment with nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME); N(G)-monomethyl-L-arginine acetate (L-NMMA) and guanylyl cyclase inhibitor, methylene blue; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and nitric oxide (NO) scavenger, hemoglobin. The increasing cGMP content induced by brazilin was also blocked by pretreatment with L-NAME, methylene blue, and the removal of extracellular Ca(2+). In human umbilical vein endothelial cells, brazilin dose-dependently induced an increase in NO formation and NOS activity, which were greatly attenuated by either the removal of extracellular Ca(2+) or the chelating of intracellular Ca(2+) chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM). Moreover, brazilin dose-dependently induced the influx of extracellular Ca(2+) in human umbilical vein endothelial cells. Collectively, these results suggest that brazilin induces vasorelaxation by the increasing intracellular Ca(2+) concentration in endothelial cells of blood vessels and hence activating Ca(2+)/calmodulin-dependent NO synthesis. The NO is released and then transferred into smooth muscle cells to activate guanylyl cyclase and increase cGMP content, resulting in vasorelaxation.