RESUMO
The effects of brazilin on glucose transport into isolated rat epididymal adipocytes were investigated. Brazilin increased [3H]2-deoxy-D-glucose uptake, which was characterized by an increase in Vmax with no effect on the Km value. Phenylarsine oxide, which inhibits the translocation of glucose transporters, decreased brazilin-stimulated glucose transport to the basal level. The inhibition of phosphatidylinositol 3-kinase (PI3-kinase) with wortmannin also blocked brazilin-stimulated glucose transport. Western blot analysis with an anti-GLUT4 antibody revealed that brazilin increased the translocation of GLUT4 from intracellular pools to the plasma membrane. Brazilin, in combination with phorbol ester, showed an additive effect on glucose transport. The stimulating effect of phorbol ester on glucose transport was inhibited by staurosporine, but the effect of brazilin remained unchanged. Protein kinase C activity was not influenced by brazilin treatment. The inhibition of protein synthesis showed no effect on brazilin-stimulated glucose transport, and GLUT4 content in the total membrane fraction was not altered as a result of treatment with brazilin for 4 hr. Metabolic labeling of GLUT4 with [35S]methionine showed that de novo synthesis of GLUT4 was not induced by brazilin. These data suggest that brazilin may increase glucose transport by recruitment of GLUT4 from intracellular pools to the plasma membrane of adipocytes via the activation of PI3-kinase. However, the effect of brazilin may not be mediated by GLUT4 synthesis and protein kinase C activation.
Assuntos
Adipócitos/efeitos dos fármacos , Benzopiranos/farmacologia , Hipoglicemiantes/farmacologia , Proteínas de Transporte de Monossacarídeos/metabolismo , Proteínas Musculares , Adipócitos/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Epididimo/citologia , Glucose/metabolismo , Transportador de Glucose Tipo 4 , Técnicas In Vitro , Masculino , Proteínas de Transporte de Monossacarídeos/biossíntese , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Brazilin (7,11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6 H)-tetrol) inhibited thrombin-,collagen- and ADP-induced aggregation of washed rat platelets. Thrombin- and collagen-induced ATP release were also inhibited by brazilin in a concentration-dependent manner. Brazilin inhibited the formation of platelet thromboxane A2 caused by thrombin, whereas it had no effect on the prostaglandin D2 formation. Brazilin inhibited [3H]-arachidonic acid liberation from membrane phospholipids of thrombin-stimulated platelets. Brazilin inhibited the rise of intracellular free calcium caused by thrombin. These results indicate that the inhibition of phospholipase (PLA2) activity and [Ca2+]i elevation might be at least a part of antiplatelet mechanism of brazilin.
Assuntos
Benzopiranos/farmacologia , Plaquetas/efeitos dos fármacos , Cálcio/metabolismo , Fosfolipases A/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Ácido Araquidônico/metabolismo , Plaquetas/metabolismo , Feminino , Técnicas In Vitro , Fosfolipases A2 , Agregação Plaquetária , Prostaglandina D2/metabolismo , Ratos , Ratos Sprague-Dawley , Tromboxano B2/metabolismoRESUMO
Previously we reported that brazilin, the main principle of Caesalpinia sappan, was able to improve the altered immune functions caused by halothane administration in mice. To elucidate the mechanisms of its immunomodulating activities, the effects of brazilin on the functions of T cells and splenic cellularity were investigated. Brazilin decreased splenic cellularity and IL-2 production which had been augmented in mice treated with halothane (21.5% in olive oil, 10 mmol/kg) for 4 consecutive days whereas the reduced expression of IL-2 receptors by ConA or standard IL-2 was increased by brazilin treatment. These data indicate that halothane induced a dysfunction of T cells resulting in abnormal immune responses and these altered immune functions might be improved mainly by affecting the function of T cells.
Assuntos
Benzopiranos/farmacologia , Halotano/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Animais , Células Cultivadas , Concanavalina A/farmacologia , Fabaceae , Feminino , Interleucina-2/biossíntese , Interleucina-2/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Lectinas de Plantas , Plantas Medicinais , Receptores de Interleucina-2/biossíntese , Baço/imunologia , Linfócitos T/imunologiaRESUMO
Brazilin increased [3H]2-deoxyglucose uptake in isolated rat epididymal adipocytes. The fact that calcium may be required for the stimulatory effects of insulin on glucose transport suggests that brazilin might also require calcium for its glucose transport-stimulating action. Changes in the concentration of extracellular calcium had no significant effect on brazilin-induced glucose transport. Nifedipine and verapamil decreased brazilin-induced glucose transport, and quin2-AM abolished the effect of brazilin on glucose transport. A23187, however, showed no effect on brazilin action. 45Ca2+ uptake into adipocytes was not influenced by brazilin treatment, and trifluoperazine significantly inhibited the effect of brazilin on glucose transport. These data suggest that calmodulin and the maintenance of the intracellular calcium concentration, rather than an increase in it, may be essential for the stimulatory action of brazilin on glucose transport.