Seong-Gon Kim

Brazilin protects cultured rat hepatocytes from BrCCl3-induced toxicity.

Brazilin, the main constituent of Caesalpinia sappan, is an antioxidative substance that has catechol moiety in its chemical structure. Considering the antioxidant-activity of brazilin, it was expected to have protective effects on the toxicities of radical generating chemicals. The incubation of rat hepatocytes with BrCCl3 resulted in significant increase in lipid peroxidation, leakage of cytoplasmic enzymes and cytoplasmic glutathione depletion. The BrCCl3-induced toxicities on hepatocytes were reduced by the treatment of brazilin. Brazilin has been also proved to have a protective effect on the BrCCl3-induced depression of microsomal calcium sequestration activity. These results indicate that brazilin plays a protective role in BrCCl3-induced hepatocyte injury of the rat.

Effects of Brazilin on glucose oxidation, lipogenesis and therein involved enzymes in adipose tissues from diabetic KK-mice.

In order to address the hypoglycemic mechanism of brazilin, effects on glucose metabolism in epididymal adipose tissue from diabetic KK-mice were investigated. Brazilin remarkably lowered non fasting plasma glucose level without any changes in plasma insulin level. Brazilin significantly increased the rate of glucose oxidation and lipogenesis only in the presence of insulin. Activities of glucose-6 phosphate dehydrogenase and fatty acid synthetase, involved in glucose oxidation and lipogenesis respectively, were significantly increased. These results suggest that brazilin might exert hypoglycemic action in insulin resistance state by, at least in part, regulating the enzymatic reaction process involved in glucose metabolism.

Brazilin inhibits activities of protein kinase C and insulin receptor serine kinase in rat liver

Hypoglycemic action of brazilin was found to be based on the improvement of peripheral glucose utility, and this action might be correlated with the insulin action pathway. In the present study we investigated the effect of brazilin on the insulin receptor autophosphorylation, protein kinase C (PKC), protein phosphatase and insulin receptor serine kinase in order to confirm whether the hypoglycemic mechanism is concerned with insulin action pathway. Brazilin was found to inhibit PKC and insulin receptor serine kinase, which are involved in the regulation of insulin signal pathway. But any significant effect was not shown on insulin receptor tyrosine kinase activity, autophosphorylation and phosphatase activity. These findings suggest that brazilin might enhance insulin receptor function by decreasing serine phosphorylation, which might mediate hypoglycemic effect of brazilin

Effects of brazilin on GLUT4 recruitment in isolated rat epididymal adipocytes.

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.

Effects of brazilin on erythrocyte deformability and its related biochemical factors in streptozotocin induced diabetic rats

Impaired erythrocyte deformability was considered to play an important role in microcirculatory disturbances. We recently confirmed that brazilin, the main active principle ofCaesalpinia sappan, enhanced activity of erythrocyte deformability and reduced blood viscosity. In this study, we examined the effects of brazilin on three biochemical parameters (ATP, 2,3-diphosphoglycerate, and calcium) which influenced erythrocyte deformability. Treatment with brazilin increased erythrocyte deformability and ATP concentrations in streptozotocin-induced diabetic rats. Concentrations of 2,3-diphosphoglycerate and calcium in diabetic rats following brazilin administration were decreased significantly compared to those of diabetic control rats. The results suggest that brazilin have a potential effect to improve rheological abnormalities in diabetes.

Effects of brazilin on glucose metabolism in primary cultured rat hepatocytes

In order to investigate the cellular mechanisms of hypoglycemic action of brazilin, hepatocyte monolayer culture was introduced and, glycogen synthesis rate and insulin binding were measured as parameters. Glycogen synthesis and insulin sensitivity were remarkably augmented by the treatment of brazilin. Brazilin slightly increased insulin binding. Scatchard analysis revealed that this increase in insulin binding was not due to increase in the binding capacity but in binding affinity. These results suggest that the augmentation of hepatic glycogenesis and insulin sensitivity by brazilin may play an important role in the improvement of hyperglycemia.

Effects of brazilin on blood viscosity and erythrocyte deformability in alloxan induced diabetic rats

Effects of brazilin on the blood viscosity and erythrocyte deformability were investigated in alloxan induced diabetic rats. By the treatment of brazilin to alloxan induced diabetic rats, enhancement of erythrocyte deformability was observed. In thein vitro study on the erythrocyte deformability, brazilin showed statistically significant improving effects on the erythrocyte deformability. At the concentrations of 10−3M of brazilin, erythrocyte deformability was compared with those of hematoxylin, pentoxifylline and prednisolone.