RESUMO
Some polyacetylenes from the plant Bidens pilosa have been reported to treat diabetes. In this study, we report that the cytopiloyne from B. pilosa, which is structurally different from the above-mentioned polyacetylenes and inhibits CD4(+) T cell proliferation, effectively prevents the development of diabetes in nonobese diabetic mice as evidenced by a normal level of blood glucose and insulin and normal pancreatic islet architecture. Cytopiloyne also suppresses the differentiation of type 1 Th cells but promotes that of type 2 Th cells, which is consistent with it enhancing GATA-3 transcription. Also, long-term application of cytopiloyne significantly decreases the level of CD4(+) T cells inside pancreatic lymph nodes and spleens but does not compromise total Ab responses mediated by T cells. Coculture assays imply that this decrease in CD4(+) T cells involves the Fas ligand/Fas pathway. Overall, our results suggest that cytopiloyne prevents type 1 diabetes mainly via T cell regulation.
Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Glucosídeos/uso terapêutico , Poli-Inos/uso terapêutico , Animais , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Feminino , Fator de Transcrição GATA3/biossíntese , Fator de Transcrição GATA3/genética , Glucosídeos/administração & dosagem , Inibidores do Crescimento/administração & dosagem , Inibidores do Crescimento/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Poli-Inos/administração & dosagem , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Timidina/metabolismo , Transcrição Gênica/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologiaRESUMO
Bidens pilosa has been used as a folk medicine in various medications and as a popular ingredient in herb teas. Chemopreventive activities of crude and fractionated plant extracts of Bidens pilosa were evaluated in this study. Ethyl acetate and butanolic fractions, partitioned from the total crude extract of Bidens pilosa, exhibited significant scavenging free radical activity (IC(50) values approximately = with 14-17 microg/mL) comparable to that of alpha-tocopherol. Strong effects on the inhibition of LPS-mediated nitric oxide production in RAW 264.7 cells were also observed for the EA and BuOH fractions. Detectable cytotoxicity on RAW 264.7 cells, however, was observed for the EA fraction at a dose >100 microg/ml. The metabolite profile and major constituents of the BuOH fraction were studied and characterized using various spectroscopic analyses. A new compound, heptanyl 2-O-beta-xylofuranosyl-(1-->6)-beta-glucopyranoside (1), and eight phenolic compounds, namely quercetin 3-O-rabinobioside (2), quercetin 3-O-rutinoside (3), chlorogenic acid (4), 3,4-di-O-caffeoylquinic acid (5), 3,5-di-O-caffeoylquinic acid (6), 4,5-di-O-caffeoylquinic acid (7), jacein (8), centaurein (9) were for the first time isolated from Bidens pilosa. Compounds 2-7 are the major antioxidative constituents in the Bidens pilosa extract.