The Hypoglycemic Mechanisms Of A Functional Component Named DMC In Cleistocalyx Operculatus (Roxb.)

2',4'-Dihydroxy-6'-methoxy-3',5'-dimethylchalcone (DMC), isolated from Cleistocalyx flower buds, possess various of pharmacological activities, such as anti-tumor, anti-bacterial, anti-inflammatory, hepatoprotective, hypoglycemic, neruoprotective activities, etc. Our previous work proved that DMC palys a key role in decreasing blood glucose and oral glucese tolerance in the alloxan-induced diabetic mice, indicating that DMC posses potential application value in diabetes prevention. In the present study, we investigated the hypoglycemic mechanism of DMC on H2O2induced MIN6cells failure. The study was conducted from the perspective of both insulin secretion and ?-cell apoptosis.In the insulin secretion research, exposition to250?M H2O2for1h was used as impaired insulin secretion model. The results showed that basal insulin secretion (BIS) and glucose-stimulated insulin secretion (GSIS) were significantly (p<0.01) decreased in the model group. However, the pretreatment with DMC at6.25-25?M piror H2O2damage has significantly increased the BIS and GSIS (p<0.01). Furthermore, the BIS and GSIS were increased by0.23ng/mL and0.69ng/mL, respectively, by25?M DMC. The results demonstrate that DMC significantly improved MIN6cells BIS and GSIS function.In the perspective of inhibiting?-cell apoptosis, the MIN6cells were exposed to250?M H2O2for3h to investigate the anti-apoptosis effects of DMC. The viability of MIN6cells were significantly decreased and the apoptosis were apparently occurred. The results showed that addition of H2O2with a pre-treatment of DMC, at the concentration of12.5-25?M, reduced nucleus fragmentation, decreased endogenous reactive oxygen species (ROS) production and improved mitochondrial potential (MMP), and consequently, inhibited apoptosis. Moreover, decreased activities of caspase-3and caspase-9were also observed. These results clearly demonstrate that DMC inhibited cell apoptosis by improving mitochondrial funtion and reducing ROS prodution.In summary, DMC ameliorates H2O2induce MIN6cells failure and inhibits cell apoptosis, which was due to its protection of mitochondrion and decrease of ROS production. The results suggest that DMC posses potential application value in diabetes prevention and treatment.