title: 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: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Glycosin acts as antihyperglycemic agent, associated with antihyperlipidemic and possibility function as a ligand for proteins that are targets for antidiabetes drugs.
authors.affiliation: Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai 608502, Tamil Nadu, India. Electronic address: gurudeeb99@gmail.com.
authors.forename: Gurudeeban
authors.initials: G
authors.lastname: Selvaraj
authors.affiliation: Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai 608502, Tamil Nadu, India.
authors.forename: Satyavani
authors.initials: S
authors.lastname: Kaliamurthi
authors.affiliation: Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai 608502, Tamil Nadu, India.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Thirugnasambandan
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007194:India; D008099:Liver / Q000187:drug effects*; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D052999:Quinazolinones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043982:Rhizophoraceae / Q000737:chemistry; D013311:Streptozocin / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D010936:Plant Extracts; D052999:Quinazolinones; D013311:Streptozocin
keywords: Diabetes mellitus; Docking; Glycosin; Mangrove; NMR; PPARγ