COMPUTATIONAL SCREENING OF ANTI-DIABETIC MOLECULES FROM MICROALGAE METABOLITES BY MOLECULAR DOCKING

Abstract

Thiazolidinediones constitute a family of antidiabetic drugs, and rosiglitasone (RSG) has an extensive usage in treating the complications of type 2 diabetes mellitus. Carvacrol (CVL), a monoterpenic phenol that occurs in many essential oils of the family Labiatae including Origanum, Satureja, Thymbra, Thymus, and Corydothymus species, possess a wide variety of pharmacological properties including antioxidant potential. We hypothesized that carvacrol in combination with RSG would prove beneficial to ameliorate the dysregulated carbohydrate metabolism in high-fat diet (HFD)-induced type 2 diabetic C57BL/6J mice. Mice were divided into six groups and fed HFD, for 10 weeks. CVL (20 mg/kg BW) and RSG (4 mg/kg BW) were administered post-orally, daily for 35 days. HFD mice showed an elevation in plasma glucose, insulin, glycosylated hemoglobin and a decrease in hemoglobin. The activities of carbohydrate metabolic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase increased whereas glucokinase and glucose-6-phosphate dehydrogenase activities decreased in the liver of HFD mice. The activities of hepatic marker enzymes such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase increased in HFD mice. Combination of CVL and RSG prevented the above changes toward normalcy. Histopathological analysis of H&E stained pancreas was also in agreement with the biochemical findings. These major findings provide evidence that combination of CVL with RSG has better antidiabetic properties.