Total Flavonoids of Mulberry Leaves Improves Liver Lipid Metabolism in Type 2 Diabetic Rats by Regulating PPAR-α/CPT-1 Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the medicinal effect of total flavonoids of mulberry leaves on regulating liver lipid metabolism disorder in diabetes mellitus type 2 （T2DM） rats， and the mechanism based on liver peroxidase proliferators activate receptors-α （PPAR-α） and carnitine palmityl transferase-1 （CPT-1） proteins. MethodTotal flavonoids of mulberry leaves were extracted and purified by ethanol extraction + macroporous resin purification and then identified. T2DM rat model was induced by high fat diet （HFD） + streptozocin（STZ）method. Rats with blood glucose ≥ 11.1 mmol·L-1 were divided into three administration groups with the high dose （300 mg·kg-1）， medium dose （150 mg·kg-1）， and low dose （75 mg·kg-1） of total flavonoids of mulberry leaves for 8 weeks， respectively， to observe the weight and blood glucose of the rats. The pathological changes of rat livers were observed by hematoxylin-eosin （HE） staining. Biochemical method was used to detect the levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein-cholesterol （LDL-C）， and high density lipoprotein-cholesterol （HDL-C） of blood lipid metabolism in rats. The messenger ribonucleic acid （mRNA） and protein expressions of PPAR-α and CPT-1 were determined by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultAfter 8 weeks of intervention of total flavonoids of mulberry leaves， compared with the control group， the food intake， liver index， and fasting blood glucose of rats in the model group increased significantly （P<0.01）. Compared with the model group， the food intake， fasting blood glucose， and liver index of rats in the administration groups decreased significantly （P<0.01）. The results of HE staining showed that the liver tissue structure of rats in the control group was complete and there was no obvious abnormality. The model group showed vacuolar degeneration and inflammatory infiltration of hepatocytes of rats. There was no obvious abnormality in the liver structure of rats in the administration groups. The results of blood lipid showed that compared with the control group， the levels of TC， TG， and LDL-C increased significantly （P<0.01）， but the level of HDL-C decreased significantly （P<0.01） in the model group. Compared with the model group， the levels of TC， TG， and LDL-C decreased significantly （P<0.05， P<0.01）， whereas the level of HDL-C increased significantly （P<0.01） in the administration groups. The results of Real-time PCR showed that compared with the control group， the mRNA expression of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the mRNA expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.01）. The results of Western blot showed that compared with the control group， the protein expressions of PPAR-α and CPT-1 of rats in the model group decreased significantly （P<0.01）. Compared with the model group， the protein expressions of PPAR-α and CPT-1 of rats in the high-dose group increased significantly （P<0.05， P<0.01）. ConclusionTotal flavonoids of mulberry leaves can effectively reduce blood glucose and improve liver lipid metabolism disorder in T2DM rats. The total flavonoids of mulberry leaves could regulate lipid metabolism and play a hypoglycemic role by activating and regulating PPAR-α and CPT-1 proteins and promoting oxidative decomposition of fatty acids.

Study on in vitro hypoglycemic effect and mechanism of Polygonum capitatum / 中草药

Objective: To investigate the hypoglycemic targets of Polygonum capitatum. Methods: Human liver cancer HepG2 cells were adopted to detect the supernatant culture medium glucose content, and the effect on PPAR-α and GLUT4 gene expression was investigated by qRT-PCR after treatment of P. capitatum extracts (PCB). INS-1 cells similar to islet β cells, divided into drug protection group and repair group, were adopted to determine the cell proliferation activity by MTT; The intracellular SOD and MDA levels were measured by biochemical method; The Cyt C and Caspase-3 protein expression levels were detected by Western blotting. Adopting maltose as substrate of α-glycosidase enzyme inhibition model, the inhibitory efficiency of PCB on glycosidic enzyme was determined. Results: PCB group significantly promoted the absorption of HepG2 cells to supernatant glucose and increased the expression of PPAR-α and GLUT4 genes significantly. Aim at protection and repair of INS-1 cells, PCB group significantly increased cell vitality and SOD level, reduced MDA level compared with model group, and at the same time significantly reduced Cyt C and Caspase-3 protein expression levels. PCB had inhibitory activity to α-glycosidase enzymes, with IC50 of 11.53 mg/mL. Conclusion: PCB could significantly increase the PPAR-α and GLUT4 genes expression to promote the absorption of HepG2 cells to supernatant glucose by blocking the Cyt C-Caspase-3 pathways to reduce apoptosis of islet cells which were damaged by STZ and by raising SOD and declining MDA to improve INS-1 cell oxidative stress; What’s more it has inhibitory activity to α-glycosidase enzymes.

Protective effect of PPAR-αagonist on PAN-induced podocyte injury / 中国药理学通报

Aim To investigate the function of fenofi-brate on PAN ( puromycin aminonucleoside )-induced podocyte injury. Methods SD female rats of 18-week-old were randomly assigned into 3 groups ( n =6 ) . Mice in PAN group and fenofibrate treated group received a single intravenous injection of PAN ( 65 mg ·kg-1 ) , while those in control group received equal volume of saline. Mice in fenofibrate treated group re-ceived 40 mg · kg-1 · d-1 of fenofibrate ( intragastric administration ) on day 1 after PAN injection , while those in PAN group and control group received equal volume of vehicle. 24 hours urine samples from all group were collected on day 0(1 day before PAN injec-tion), day 6, day 10. The 24 hours urine protein was detected by Bradford assay. All the rats were sacrificed 10 days after the induction of podocyte injury, and glo-merulus sample were collected. The expression of podocyte injury marker and transcription level in apop-tosis, podocyte cytoskeleton protein, slit diaphragm protein were evaluated by Western blot and real-time PCR. Results Compared with the control group, 10 days after injection of PAN, 24 hours urine protein was obviously increased, and the expression and transcrip-tion level of podocyte injury marker desmin, apoptosis, podocyte cytoskeleton protein, slit diaphragm protein were upregulated greatly, however, those were signifi-cantly lower in fenofibrate treated group as compared with those in PAN group. Conclusions PPAR-α ago-nist fenofibrate can ameliorate PAN-induced glomerulus podocyte injury, and the mechanism involved may be associated with inhibition of the mitochondria apopto-sis, TGF-β/Smad pathway and p38 pathway.

Astragalus polysaccharides improves glycolipid metabolism in myocardium of diabetic hamsters / 中华内分泌代谢杂志

e tissue and myocardium, as well as myocardial uhrastructure were well-improved; the gene expressions of PPAR-α and GLUT4 were raised in APSgroup. APS may be partially effective in treating diabetic cardiomyopathy.

Effects of fenofibrate and pioglitazone on expressions of intracellular signaling molecules in pancreatic islet of high-fat diet-fed rats / 中华内分泌代谢杂志

Objective To observe the effects of fenofibrate and pioglitazone on the expressions of PPAR- α, PPAR-γ, and intracellular signaling molecules in pancreatic islets of obese rats induced by high-fat diets. Methods SD obese rat models were established with high-fat diet, and 40 male rats were assigned to 4 groups including high-fat diet (HF group), high-fat diet with fenofibrate (FF group), pioglitazone (FP group) treatment, and control rats with normal diet (NC group). After 8 weeks intervention, immunohistochemistry was performed to evaluate the expressions of various proteins in islets; At the same time, islets mass were scored in tissue slides. Results Islets mass enlarged in HF group. The compositions of islet cells were the same as the control. The expression of insulin was lower in HF group than the control, but after using pioglitazone, less islets mass and more insulin expression were found in FP group. Compared with the control group, expressions of PPAR-α, PPAR-γ protein were reduced in HF group, and the expression of PPAR-α protein increased in FF group, and the expression of PPAR-γ protein was increased in FP group. The levels of NF-кB, p38 mitogen-activated protein kinase (MAPK), ERK1 proteins increased significantly in HF group, the expressions of NF-кB, p38 MAPK decreased in FF and FP groups, and the level of ERK1 decreased only in FP group, the protein level of I-кB showed no difference among control, HF group, and FF groups. Conclusion Fenofibrate and pioglitazone may partially protect islet cells function and improve survival by correcting the disturbance of intracellular signaling molecules.