Studies On Protective Effects And Mechanisms Of Salidroside On ?-cells

With the prevalence of obesity and unhealthy lifestyle,diabetes has become one of the three fatal non-communicable diseases.It is noteworthy that oxidative stress is one of the important factors which contribute to the progression of type 2 diabetes mellitus,insulin resistance even ? cell failure.Traditional Chinese medicine has a long history in treating "XIAO KE" which we called it diabetes for a long time.People living in Tibet has used Rhodiola to keep out the impact of the hypoxic environment in Plateau since two thousand years ago.Oxidative stress plays an important role in inducing ?-cell failure.Reactive oxygen species?ROS?is one of the most important factors that result in defective metabolism and secretion of insulin in ?-cells.Salidroside is the major active ingredient of Crassulaceae rhodiola.Modern pharmacological studies also showed that Salidroside was effective in ameliorating diabetes.While its role in protecting pancreatic ? cells is still not clear.In this paper,animal and cell models were used to explore the protective effect of Salidroside on pancreatic ? cells.On the other hand,through the study,we hoped to establish a new way to search the mechanism of hypoglycemic effects of traditional Chinese Medicine.The results were as follows: 1.Hypoglycemic effect and mechanism of salidroside on HFD or db/db diabetic miceThe OGTT test after the administration of Salidroside for 35 days showed that Salidroside could depress the level of fasting blood glucose,improve the function of ? cell.Further study revealed that Salidroside could also significantly decrease the levels of TG and CHO in HFD induced diabetic mice,which suggested the improvement of lipid metabolism and insulin resistance in diabetic mice.In addition,a inecreasing in activity of SOD?Superoxide dismutase?or CAT?Catalase?was also observed in adipose tissues of Salidroside treatment group mice.Immunofluorescence of pancreatic tissue also confirmed the protective effect of Salidroside on pancreatic ? cells.At the same time,db/db diabetic mice also showed the similar results that Salidroside could depress the level of fasting blood glucose,improved the function of ? cell.In addition,an increase in activity of SOD?Superoxide dismutase?or CAT?Catalase?was also observed in mice adipose tissue of Salidroside treatment group.Immunofluorescence of pancreatic tissue also confirmed the protective effect of Salidroside on pancreatic ? cells.Thus,we believed that salidroside could ameliorate the fasting blood glucose,improve lipid metabolism disorder and normalize the function of ? cells through the study of HFD induced diabetic mouse model.Through the two classic animal models above,it suggested that hat salidroside could improve the symptoms of type 2 diabetes mellitus,promote?cell proliferation and improved?cell mass.2.Effects of salidroside on pancreatic beta cellsIn order to investigate the molecular mechanism of Salidroside,mouse islets were isolated from C57BL/6J mice by common bile duct perfusion..Under high glucose or H₂O₂ conditions,we assume that salidroside may inactivate FOXO1 via stimulating AMPK/AKT pathway to enhance PDX1 functions and improve ?-cell survival.We used mouse primary ? cells and simulated diabetic environments by high glucose,high concentrations of free fatty acids,inflammatory factor stimulation or oxidative stress.Salidroside could improve the symptoms of type 2 diabetes by inhibiting the apoptosis of ? cells and promoting the regeneration of ? cells.3.Protective effects of Salidroside on ? cells injury and its mechanism.On the other hand,we also choosed the pancreatic ? cell line?MIN6?to study the protective effects of Salidroside on ?cells injury and its mechanism.It suggested that Salidroside improved ?-cell survival under diabetic condition.As a natural antioxidant,salidroside effectively suppressed ROS production and recovered ??m in Min6 cells compared to DMSO-treated.In addition,Salidroside down-regulated the NOX2 expression and inhibited subsequent activations of JNK and caspase 3 to prevent ?-cell death.Also,with salidroside treatment,PDX1 translocated into the nucleus,and nuclear exclusion of FOXO1 was observed.The nuclear/cytosolic ratio of PDX1 was significantly elevated by salidroside compared to DMSO-treated cells to improve the ?-cell function and survival.In this study,the main active component of Rhodiola rosea Salidroside was selected as the research object and we tried to establish a new way to study the mechanism of hypoglycemic effect of traditional Chinese medicine.It would be helpful to understand the reason of ? cell failure in type 2 diabetes,and elucidated the role of ROS in ? cell function.Also,we explored the new mechanism of traditional Chinese medicine in depressing blood glucose to develop new hypoglycemic agents of Chinese herbs.