ABSTRACT
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.
Subject(s)
Biological Transport , Dose-Response Relationship, Drug , Fruit , Gene Expression , Glucose , Metabolism , Glucose Transporter Type 4 , Metabolism , Hypoglycemic Agents , Pharmacology , In Vitro Techniques , Insulin , Metabolism , Momordica , Muscle Fibers, Skeletal , PPAR gamma , Metabolism , Plant Extracts , Pharmacology , Protein Biosynthesis , Protein Synthesis Inhibitors , Pharmacology , Rosiglitazone , Thiazolidinediones , Pharmacology , Up-RegulationABSTRACT
The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 [3-[methyl]-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one], CP-2 [3-[ethyl]- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one] and CP-6 [3-[2-chloro phenyl]-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one] against dexamethasone and Triton WR-1339-induced hyper- lipidemia in rats. Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone [10 mg/kg, subcutaneous [s.c.]] and Triton WR-1339 [200 mg/kg, intraperitoneal [i.p]] induced hyperlipidemia in rats. Administration of single dose of Triton WR-1339 [200 mg/kg i.p] and dexamethasone [10 mg/kg s.c.] for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compare to normal control. Pretreatment with Atorvastatin [10 mg/kg, p.o.], CP-1 [25 and 50 mg/kg], CP-2 [25 and 50 mg/kg] and CP-6 [25 and 50 mg/kg] showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2. These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia