title: In vivo anti-diabetic, antioxidant and molecular docking studies of 1, 2, 8-trihydroxy-6-methoxy xanthone and 1, 2-dihydroxy-6-methoxyxanthone-8-O-β-D-xylopyranosyl isolated from Swertia corymbosa.
abstract: 1, 2, 8-trihydroxy-6-methoxy xanthone (1) and 1, 2- dihydroxy-6-methoxyxanthone-8-O-β-d-xylopyranosyl (2) are the main constituents of petroleum ether and ethyl acetate extracts from Swertia corymbosa (Gentinaceae), a medicinal plant used in Indian traditional system for the treatment of diabetes. The present study was designed to examine the antihypoglycemic, antihyperlipidemic and antioxidant effect of compounds 1 and 2 in streptozotocin (STZ) induced diabetic rats. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (60 mg/kg b.w.). The isolated compounds 1 and 2 at a dose of 50 mg/kg b.w., produced the maximum fall of 83% in the blood glucose level in the diabetic rats after 3h of the treatment. The administration of 1 and 2 (50 mg/kgb.w.) daily for 28 days in STZ induced diabetic rats, resulted in a significant decrease in blood glucose, glycosylated hemoglobin, SGOT, SGPT, ALP serum urea and creatinine with significant rise in plasma insulin level. Test compounds 1 and 2 showed antihyperlipidemic activities as evidenced by significant decrease in serum TC, TG, LDL-C, VLDL-C levels coupled together with elevation of HDL-C level in diabetic treated rats when compared to diabetic untreated rats, indicate the protective role against liver and kidney damage. The results of histopathology also showed 1 and 2 protected tissues (pancreas, liver and kidney) against peroxidation damage and maintained tissue integrity. Further, the molecular interaction study of the ligands 1, 2 and glibenclamide with various diabetes mellitus related protein targets like glucokinase (PDB ID: 1V4S), fructose-1, 6-bisphosphatase 1 (PDB ID: 2JJK) 11-β-hydroxysteroid dehydrogenase (PDB ID: 2BEL) and modeled protein sulfonylurea receptor 1 (SUR1) showed that ligand 1 and 2 possess binding affinity with all protein targets except for 2BEL target protein for which ligand 1 has no interaction. The ligand pose with 2BEL and SUR1 protein target of ligand 2 gave the best binding conformation. Hence 1 and 2 can be considered for developing into a potent antidiabetic drug.
authors.affiliation: Plant Tissue Culture Laboratory, Department of Botany, School of Life Sciences, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India. Electronic address: mahendran0007@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Mahendran
authors.affiliation: Department of Chemistry, School of Chemical Sciences, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: M
authors.initials: M
authors.lastname: Manoj
authors.affiliation: Computational Biology Lab, Bioinformatics Department, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: E
authors.initials: E
authors.lastname: Murugesh
authors.affiliation: Computational Biology Lab, Bioinformatics Department, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: R
authors.initials: R
authors.lastname: Sathish Kumar
authors.affiliation: Computational Biology Lab, Bioinformatics Department, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: P
authors.initials: P
authors.lastname: Shanmughavel
authors.affiliation: Department of Chemistry, School of Chemical Sciences, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: K J
authors.initials: KJ
authors.lastname: Rajendra Prasad
authors.affiliation: Plant Tissue Culture Laboratory, Department of Botany, School of Life Sciences, Bharathiar University, Coimbatore 641 046, Tamil Nadu, India.
authors.forename: V
authors.initials: V
authors.lastname: Narmatha Bai
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D008517:Phytotherapy; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D017208:Rats, Wistar; D029967:Swertia / Q000737:chemistry*; D023382:Toxicity Tests, Acute; D044004:Xanthones / Q000494:pharmacology
chemical_list: C000596090:1,2,8-trihydroxy-6-methoxyxanthone; C000596091:1,2-dihydroxy-6-methoxy-8-O-xylopyranosylxanthone; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D010936:Plant Extracts; D044004:Xanthones
keywords: 2BEL; Antidiabetic activity; Antioxidant; SUR1; Swertia corymbosa; Xanthones