ABSTRACT
Glimepiride sulfonamide (GS) is a drug intermediate to synthesize glimepiride (antidiabetic drug). We hypothesized that GS exerts gluco-regulatory effect because GS is comprised of the structural components of dipeptidyl peptidase-IV (DPP-IV) inhibitors sitagliptin and DPP-728and glimepiride (sulfonylurea based antidiabetic drug).We analyzed the drug-likeness and docking efficiency of GS with DPP-IV using in silico tools. Also DPP-IV inhibition assays were conducted in vitro. Gluco-regulatory potential and parameters of drug safety were evaluated on normal euglycemic and streptozotocin (STZ) induced diabetic rats. We observed strong drug-likeness and DPP-IV binding efficiency of GS. Similarly, profound DPP-IV inhibition was also observed in vitro. Studies on euglycemic and STZ induced diabetic rats revealed antidiabetic potential for GS without significant change in the studied toxicological parameters. Glimepiride sulfonamide has antidiabetic potential mainly through DPP-IV inhibition, but also through insulin stimulation and alpha-amylase inhibition.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Sulfonamides/pharmacology , Sulfonylurea Compounds/pharmacology , Animals , Computer Simulation , Diabetes Mellitus, Experimental/physiopathology , Dipeptidyl Peptidase 4/drug effects , Dipeptidyl Peptidase 4/metabolism , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Female , Hypoglycemic Agents/chemistry , Insulin/metabolism , Molecular Docking Simulation , Rats , Rats, Wistar , Streptozocin , Sulfonamides/chemistry , Sulfonylurea Compounds/chemistryABSTRACT
The incretin based therapies are an emerging class of antidiabetic drugs, with two categories: one is glucagone like peptide-1 (GLP-1) agonists and the other one is dipeptidyl peptidase (CD26; DPP-IV) inhibitors. However, in the DPP-IV inhibitors category only few compounds are commercially available and also have some undesirable effects. Therefore, in the present work we tried to explore a naturally occurring compound naringin for its potential DPP-IV inhibition and antidiabetic potential. It is noteworthy that this compound is abundantly present in orange peel and thus may provide cost effective treatment for diabetes, especially type 2 diabetes mellitus. In the present study, we have conducted virtual docking study and observed tight binding of naringin, as shown by higher negative values of H bond lengths, while in vitro DPP-IV inhibition assay has also shown better inhibition by naringin. In vivo study, in response to 10 days administration of 40 mg/kg of naringin twice daily to Wistar albino rats, inhibited the serum levels of DPP-IV activity, random glucose concentration with concomitant increase in insulin levels. All the comparisons were made with the standard commercially available drug sitagliptin.
