OBJECTIVE: To observe the effect and mechanism of avandia and puerarin used in combination for diabetic nephropathy. METHODS: A total of 180 patients with diabetic nephropathy were randomly divided into 3 groups. The control group (58 patients, group A) were treated with routine therapy including controlling the blood glucose and blood pressure, while 60 patients in group B were treated by avandia besides routine treatment of the control group. Anoter 62 cases in group C were administered with puerarin combined with avandia for 12 weeks. The indexes such as urea nitrogen, serum creatinine, triglyceride, cholesterol, low density lipoprotein, high density lipoprotein, mean arterial pressure, fasting blood glucose, 2h plasma glucose, glycosylated hemoglobin, and 24 h urinary albumin excretion rate were tested before and after the treatment . RESULTS: No significant differences were found in the indexes such as triglyceride, serum cholesterol, low density lipoprotein, high density lipoprotein, glycosylated hemoglobin, malonaldehyde, erythrocuprein, blood urea nitrogen, serum creatinine and 24 h urinary albumin excretion rate among the 3 groups (P>0.05). There were no significant differences in all indexes before and after the treatment in group A (P>0.05) . After the treatment, 24 h urinary albumin excretion, urea nitrogen, serum creatinine, mean arterial pressure, fasting blood glucose, 2 h plasma glucose, glycosylated hemoglobin, triglyceride, serum cholesterol, low density lipoprotein decreased significant (P<0 05) while high density lipoprotein increased significant (P<0.05). CONCLUSION Avandia has better effect on adjusting the blood lipid and decreasing the urinary albumin excretion rate. Puerarin combined with avandia is more effective for improving the renal function and remission of islet function than using avandia alone. Puerarin and avandia have significant synergism.
Adult ; Aged ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Nephropathies ; drug therapy ; etiology ; Drug Therapy, Combination ; Female ; Humans ; Isoflavones ; therapeutic use ; Male ; Middle Aged ; Rosiglitazone ; Thiazolidinediones ; therapeutic use

Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H₂O₂)-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H₂O₂ on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host's antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.
Mice ; Humans ; Rats ; Animals ; Swine ; PPAR gamma/pharmacology* ; Reactive Oxygen Species/pharmacology* ; Heterografts ; Hydrogen Peroxide/pharmacology* ; Rats, Sprague-Dawley ; Rosiglitazone/pharmacology* ; Oxidative Stress

OBJECTIVE: To explore the effect of rosiglitazone (ROS) on proliferation of human laryngeal carcinoma Hep-2 cells and it's mechanism. METHOD: Methabenzthiazuron (MTT) was used to observe the proliferation of human laryngeal carcinoma Hep-2 cells by various concentrations of ROS at different times. Flow cytometry (FCM) used to measure the cell cycle and apoptosis rate. RT-PCR was used to measure the expression of cyclooxygenase-2 (COX-2) mRNA. RESULT: The inhibited growth of ROS to Hep-2 cells in a dose-dependent and time-dependent manner (P < 0.01). The cell cycle was arrested in G0/G1 phase, which with a typical sub G1 peak, and the apoptosis rate increased in a time-dependent manner (P < 0.05). The expression of COX-2 mRNA in Hep-2 cells was significantly down-regulated by ROS (P < 0.01). CONCLUSION The function of growth inhibition and apoptosis induction of ROS on human laryngeal cancer Hep-2 cells was obvious, and its mechanism was related to block cell cycle at the G0/G1 phase and decrease the expression of COX-2.
Apoptosis ; drug effects ; Carcinoma, Squamous Cell ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 ; metabolism ; Humans ; Hypoglycemic Agents ; pharmacology ; Laryngeal Neoplasms ; metabolism ; Rosiglitazone ; Thiazolidinediones ; pharmacology

OBJECTIVE: To investigate the effects of rosiglitazone on endothelium-dependent vasodilation in patients with Type 2 diabetes. METHODS: Eighty-three newly diagnosed patients with Type 2 diabetes were divided into metformin group (metformin 750 mg/d), therapeutic alliance group (rosiglitazone 4 mg/d and metformin 750 mg/d), and rosiglitazone group (rosiglitazone 4 mg/d), and 25 normal subjects were as the control group. All patients were treated for 12 weeks. The height, weight, blood pressure, fasting plasma glucose (FPG), fasting serum insulin (FINS), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and serum nitric oxide (NO) were measured before and after the therapy. The body mass index (BMI) and homeostasis model assessment-insulin resistant index (HOMA-IR) were calculated. The flow-mediated dilatation (FMD) and endothelium independent dilatation (EID) were measured by high-resolution ultrasound. RESULTS: The BMI, TG, TC, LDL-C, FPG, HBA1c, HOMA-IR were higher (P<0.01), but HDL-C, NO, FMD were lower (P<0.01) in all diabetic groups than those in the control group before the treatment. After the 12-week treatment, TG, FPG, HBA1c, HOMA-IR decreased significantly in all the diabetic groups (P<0.01); FINS decreased, but HDL-C, NO, FMD and EID increased (P<0.01) in therapeutic alliance group and rosiglitazone groups, while HDL-C, FINS, NO, FMD had no change in metformin group compared with those before the treatment. CONCLUSION Endothelium-dependent vasodilation function is impaired in patients with Type 2 diabetes. The therapy with rosiglitazone can increase the serum NO level, and improve endothelium-dependent vasodilation,but metformin has no influence on the above-mentioned indexes.
Adult ; Diabetes Mellitus, Type 2 ; drug therapy ; physiopathology ; Female ; Humans ; Hypoglycemic Agents ; therapeutic use ; Male ; Middle Aged ; Prospective Studies ; Rosiglitazone ; Thiazolidinediones ; therapeutic use ; Vasodilation ; drug effects ; Vasodilator Agents ; therapeutic use

OBJECTIVE: To investigate the change of carotid intima-media thickness (IMTc) and serum matrix metalloproteinases-9 (MMP-9) levels in newly diagnosed Type 2 diabetic patients, and to analyze the relationship between MMP-9 and IMTc; at the same time, to assess the effect of rosiglitazone on IMTc and MMP-9 levels. METHODS: Fifty-eight patients with Type 2 diabetes mellitus were selected in our study, and 25 healthy adults served as normal controls. Diabetic patients were divided into 2 groups: Group A (31 subjects) were treated with rosiglitazone (4 mg/d), and Group B (27 subjects) were treated with metformin alone (500 approximately 1,500 mg/d). They all received the treatment for 3 months. The IMTc was measured by high resolution ultrasonography, and the serum MMP-9 was determined by enzyme linked immunosorbent assay (ELISA) to assess the relationship between IMTc and MMP-9. RESULTS: The mean level of serum IMTc and MMP-9 in Type 2 diabetic patients was significantly higher than that in healthy adults (P < 0.05). After treatment with rosiglitazone and metformin, IMTc and serum MMP-9 levels decreased significantly (P < 0.05). There was no obvious change in IMTc and serum MMP-9 levels in group B before and after the treatment (P = 0. 071, P = 0.065). Using multiple linear stepwise regression analysis, the significant correlation between IMTc and HbA1C, BMI, WHR, HDL-C, MMP-9 were discovered. CONCLUSION IMTc and MMP-9 levels increase in newly diagnosed Type 2 diabetic patients, suggesting that there is closely relationship between serume MMP-9 levels and early diabetic macrovascular disease. IMTc and MMP-9 can be reduced significantly in the newly diagnosed diabetic patients after being treated with rosiglitazone, which may be one of the protective mechanisms of vascular vessels.
Adult ; Carotid Arteries ; pathology ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; pathology ; Female ; Humans ; Hypoglycemic Agents ; therapeutic use ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Rosiglitazone ; Thiazolidinediones ; therapeutic use ; Tunica Intima ; pathology ; Tunica Media ; pathology

OBJECTIVE: To observe the effect of rosiglitazone on the production of nitric oxide (NO) and the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) /the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells(HUVECs), and to investigate the mechanism of signal transduction of rosiglitazone in improving the endothelial function. METHODS: HUVECs were treated with various concentrations of rosiglitazone. The NO level was measured using Griess Reaction in cell culture supernatants; the expressions of PI3K-, PKB- and eNOS mRNA were measured using RT-PCR; and the expressions of PKB, eNOS, and phosphorylation of PKB-Ser473, eNOS-Ser1177 were measured using Western Blot. RESULTS: Rosiglitazone increased the endothelial NO production in a dose- and time-dependent manner in cultured HUVECs, and also increased the expression of PI3K mRNA and the phosphorylation of PKB-Ser473 and eNOS-Ser1177 in a concentration-dependent manner, with no alteration in the expression of PKB and eNOS in cultured HUVECs. N(w)-nitro-L- arginine methyl ester (L-NAME, eNOS synthase inhibitor) blocked the rosiglitazone-induced NO formation; LY294002 (a PI3K inhibitor) prevented the NO production; and the phosphorylation of eNOS and PKB was induced by rosiglitazone. CONCLUSION Treatment with rosiglitazone can increase the NO production and improve the endothelial function through up-regulating the PI3K/PKB/eNOS signal pathways in cultured HUVECs.
Cells, Cultured ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rosiglitazone ; Signal Transduction ; drug effects ; Thiazolidinediones ; pharmacology

OBJECTIVE: To investigate the effect of administration of rosiglitazone, an artificial ligand of PPARγ, on the expression and secretion of apolipoprotein (apoM) in fat-fed, streptozotocin-treated rats, an animal model for type 2-like diabetes. METHODS: Healthy male SD rats were divided into 4 groups: a control group (n=7), a high-fat chow group (HF group, n=8), a diabetes mellitus group (DM group, n=7), and a diabetes mellitus group with rosiglitazone intervention group (RSG group, n=7). Fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG) and total cholesterol (TC) were measured at the beginning of the study. The diabetic rats model was established by feeding high fat chow and intraperitoneal injection of streprozotocin. Then the randomly selected treatment group was given rosiglitazone by daily gavage for 8 weeks. All the rats were killed at the fifteenth week, at which time blood and tissues (liver, kidney, adipose) were collected and prepared. The levels of FBG, FINS, TG and TC were assayed. The level of apoM in serum was measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used to determine apoM mRNA expression in liver, kidney, and adipose tissues. RESULTS: Compared with either control group or HF group, serum apoM concentration in the DM group was reduced significantly (P<0.05); compared with the DM group, however, serum apoM concentrations in RSG group were increased (P<0.05). The expression of apoM mRNA in liver was highest, in kidney medium, and in adipose tissue extremely low (P<0.05). ApoM mRNA expression in liver and kidney was decreased in both DM and HF groups compared to control group (P<0.05). But, as with serum apoM concentration, apoM mRNA in the liver, kidney and adipose tissues of the RSG group were all increased markedly (P<0.05). The level of serum apoM in SD rats correlated negatively with TG (r=-0.466, P=0.011), TC (r=-0.568, P= 0.001), FBS (r =-0.371, P<0.001), and FINS(r=-0.768, P= 0.048 ). CONCLUSION These results suggest that apoM may participate in the glucose and lipid metabolism by the regulation of PPARγ.
Animals ; Apolipoproteins ; blood ; genetics ; metabolism ; Apolipoproteins M ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Dietary Fats ; administration & dosage ; Lipocalins ; blood ; genetics ; metabolism ; Male ; PPAR gamma ; agonists ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rosiglitazone ; Thiazolidinediones ; therapeutic use

The present study was undertaken to evaluate the influence of the methanolic fruit extract of Momordica cymbalaria (MFMC) on PPARγ (Peroxisome Proliferator Activated Receptor gamma) and GLUT-4 (Glucose transporter-4) with respect to glucose transport. Various concentrations of MFMC ranging from 62.5 to 500 μg·mL(-1) were evaluated for glucose uptake activity in vitro using L6 myotubes, rosiglitazone was used as a reference standard. The MFMC showed significant and dose-dependent increase in glucose uptake at the tested concentrations, further, the glucose uptake activity of MFMC (500 μg·mL(-1)) was comparable with rosigilitazone. Furthermore, MFMC has shown up-regulation of GLUT-4 and PPARγ gene expressions in L6 myotubes. In addition, the MFMC when incubated along with cycloheximide (CHX), which is a protein synthesis inhibitor, has shown complete blockade of glucose uptake. This indicates that new protein synthesis is required for increased GLUT-4 translocation. In conclusion, these findings suggest that MFMC is enhancing the glucose uptake significantly and dose dependently through the enhanced expression of PPARγ and GLUT-4 in vitro.
Biological Transport ; Dose-Response Relationship, Drug ; Fruit ; Gene Expression ; drug effects ; Glucose ; metabolism ; Glucose Transporter Type 4 ; metabolism ; Hypoglycemic Agents ; pharmacology ; In Vitro Techniques ; Insulin ; metabolism ; Momordica ; Muscle Fibers, Skeletal ; drug effects ; PPAR gamma ; metabolism ; Plant Extracts ; pharmacology ; Protein Biosynthesis ; Protein Synthesis Inhibitors ; pharmacology ; Rosiglitazone ; Thiazolidinediones ; pharmacology ; Up-Regulation

To explore the protective effect of rosiglitazone (RGZ) on hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms.
 Methods: A rat model of ischemia-reperfusion injury was established by clamping the left and middle lobe of liver with noninvasive vascular clamp. A total of 30 Sprague-Dawley rats were randomly divided into a sham group, an HIRI group, and a RGZ group (10 rats in each group). Two hours after reperfusion, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, lactate dehydrogenase (LDH) level, malondialdehyde (MDA) content and catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were examined. HE staining was used to observe liver pathological morphology. The liver peroxisome proliferators-activated receptor γ (PPAR-γ), p-PPAR-γ, nuclear factor related factor 2 (Nrf-2), antioxidant response element (ARE), heme oxygenase 1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were detected by Western blot.
 Results: Compared with the HIRI group, the levels of ALT, AST, LDH and MDA in the RGZ group were significantly decreased (all P<0.05), while the levels of Nrf-2, ARE, HO-1 and NQO-1 in the RGZ group were significantly increased. The hepatic swelling, necrosis and pathological damage were decreased (all P<0.05). In addition, there was no difference in the level of PPAR-γ between the 2 groups (P>0.05).
 Conclusion: PPAR-γ agonist RGZ can attenuate HIRI, which may be related to activating Nrf2/ARE signaling pathway and enhancement of antioxidant ability.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Catalase ; blood ; Disease Models, Animal ; Glutathione Peroxidase ; blood ; L-Lactate Dehydrogenase ; blood ; Ligation ; Liver ; blood supply ; metabolism ; Malondialdehyde ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; blood ; etiology ; prevention & control ; Rosiglitazone ; Superoxide Dismutase ; blood ; Thiazolidinediones ; therapeutic use