Effect of Glycosin alkaloid from Rhizophora apiculata in non-insulin dependent diabetic rats and its mechanism of action: In vivo and in silico studies

Abstract

Background and aim: Diabetes mellitus is a complex multifactorial disorder that remains a great challenging task in the clinical practice. Rhizophora apiculata from Indian medicinal mangrove is widely used to treat inflammation, wound healing and diabetes. Bioassay guided fractionation was followed to isolate Glycosin from the ethanolic extract of R. apiculata. The antidiabetic effect of Glycosin in diabetic rats was investigated and determined their possible mechanism of action.

Methods: Diabetes was induced in adult Wistar rats by a single intraperitoneal injection of streptozotocin and nicotinamide. Based on the oral glucose tolerance test, Glycosin (50mg/kg b.wt.) was orally administrated to diabetic rats for a period of 45 days. In different intervals, blood glucose and body weight were recorded. After 45 days, blood samples were collected to determine serum lipid profile, level of plasma insulin, hemoglobin, liver, and kidney functions using the appropriate tests. In addition the levels of carbohydrate metabolic enzymes in the liver homogenate were also measured. To determine the molecular mechanism of action, we followed the molecular docking of Glycosin in its possible targets, dipeptidyl peptidase-IV (DPP-IV), Peroxisome proliferator-activated receptor gamma (PPARγ), phosphorylated insulin receptor, and protein tyrosine phosphatase 1B (PTP-1B).

Results: Glycosin treatment significantly (p<0.01) reduced the blood-glucose level, increased the body weight, increase hemoglobin, high-density lipoprotein and insulin level, protein, in addition the activity of hexokinase when compared to untreated rats. Decreased activities of liver function enzymes as well as level of urea, and creatinine were observed in Glycosin treated rats. Docking simulation confirmed that Glycosin interacted with DPP-IV, Insulin receptor and PTP-1B and PPARγ with more affinity and binding energy.

Conclusion: Glycosin acts as antihyperglycemic agent, associated with antihyperlipidemic and possibility function as a ligand for proteins that are targets for antidiabetes drugs.

Keywords: Diabetes mellitus; Docking; Glycosin; Mangrove; NMR; PPARγ.