Novel Triterpenoids from Cassia fistula Stem Bark Depreciates STZ-Induced Detrimental Changes in IRS-1/Akt-Mediated Insulin Signaling Mechanisms in Type-1 Diabetic Rats.

Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p < 0.05). Plasma insulin (p < 0.0001)/C-peptide (p < 0.0006), tissue glycogen (p < 0.0034), glycogen phosphorylase (p < 0.005), glucose 6-phosphatase (p < 0.0001) and lipid markers were significantly increased (p < 0.0001) in diabetic rats, whereas glucokinase (p < 0.0047), glycogen synthase (p < 0.003), glucose oxidation (p < 0.001), GLUT4 mRNA (p < 0.0463), GLUT4 protein (p < 0.0475) and the insulin-signaling molecules IR mRNA (p < 0.0195), IR protein (p < 0.0001), IRS-1 mRNA (p < 0.0478), p-IRS-1Tyr612 (p < 0.0185), Akt mRNA (p < 0.0394), p-AktSer473 (p < 0.0162), GLUT4 mRNA (p < 0.0463) and GLUT4 (p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1-C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1-C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.

ß-cell regenerative efficacy of a polysaccharide isolated from methanolic extract of Tinospora cordifolia stem on streptozotocin -induced diabetic Wistar rats.

The use of herbal supplements either as extracts or plant-derived individual molecules has significantly increased in the process of drug discovery and development for their potential efficacy or reduced risk in treating human disorders. Tinospora cordifolia (T. cordifolia) is a widely used herbal source to treat various human ailments, including diabetes mellitus. The present study was aimed on evaluating the antidiabetic property of a novel polysaccharide isolated from the methanolic extract of T. cordifolia stem. Bioassay guided fractionation was followed to isolate a compound from the methanol extract. The compound was administered orally at a dose of 20 mg/kg.b.wt for 60 days to control and STZ-induced diabetic male Wistar rats. It was found that plasma glucose was significantly (p < 0.05) reduced compared to normal. Oral administration of the compound significantly decreased HBA1c, triglycerides and total cholesterol and at the same time markedly increased hemoglobin, tissue glycogen and HDL cholesterol. Also the compounds restored the altered carbohydrate metabolizing enzymes, insulin, C-peptide, (14)C-glucose oxidation levels to near normal. In addition, the histological studies revealed that there was regeneration of ß-cells in the pancreatic sections. The expression of Glut-4 mRNA and protein in the gasrtocnemius muscle were significantly enhanced after the compound treatment. These results confirm that the novel polysaccharide possesses hypoglycemic, glucose oxidizing, hypolipidemic and ß-cell regenerative properties and hence it could be developed into potential oral hypoglycemic drug with lesser side effects.

Virtual screening of potential inhibitor against FtsZ protein from Staphylococcus aureus.

The gram-positive bacterium Staphylococcus aureus, responsible for a wide variety of diseases in human involve all organ systems ranging from localized skin infections to life-threatening systemic infections. FtsZ, the key protein of bacterial cell division was selected as a potent anti bacterial target. In order to identify the new compounds structure based screening process was carried out. An enrichment study was performed to select a suitable scoring function and to retrieve potential candidates against FtsZ from a large chemical database. The docking score and docking energy values were compared and their atomic interaction was also evaluated. Furthermore molecular dynamics simulation were also been performed to check the stability and the amino acids interacted towards the FtsZ. Finally we selected C ID 16284, 25916, 15894, 13403 as better lead compounds. From these results, we conclude that our insilico results will provide a framework for the detailed in vitro and in vivo studies about the FtsZ protein activity in drug development process.