title: Antidiabetic activity of benzopyrone analogues in nicotinamide-streptozotocin induced type 2 diabetes in rats.
abstract: Benzopyrones are proven antidiabetic drug candidate in diabetic drug discovery. In this view novel synthetic benzopyrone analogues were selected for testing in experimental diabetes. Type 2 diabetes (T2D) was induced in Wistar rats by streptozotocin (60 mg/kg, i.p.) followed by nicotinamide (120 mg/kg i.p.). Rats having fasting blood glucose (FBG)>200 mg/dL, 7 days after T2D-induction, are selected for the study. Test compounds and standard treatment were continued for 15 days. FBG, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were determined on 21st day after induction of T2D. Plasma lipids and serum insulin were estimated. Homeostatic model assessment (HOMA-IR) was then calculated from serum insulin. Rats were sacrificed and pancreas was isolated for histopathological observations. Oxidative stress markers were estimated in liver homogenate. Quercetin, a natural product with benzopyrone ring, showed significant hypoglycemic activity comparable to glibenclamide. Treatment with test compounds lowered the FBG and insulin resistance was significant alleviated as determined by OGTT, HOMA-IR, and ITT. There was significant normalisation of liver antioxidant enzymes compared to diabetic rats indicating that all the synthesised benzopyrone analogues are beneficial in reducing oxidative stress and are on par with the standard quercetin and glibenclamide in experimental T2D.
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Yogendra
authors.identifier: 0000-0002-0508-1394
authors.initials: Y
authors.lastname: Nayak
authors.affiliation: Department of Chemistry, Kasturba Medical College International Centre, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: Venkatachalam
authors.identifier: 0000-0002-4506-7343
authors.initials: V
authors.lastname: Hillemane
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India ; College of Pharmacy, Anjarakandy Integrated Campus, Kannur, Kerala 670612, India.
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Daroji
authors.affiliation: Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Jayashree
authors.affiliation: Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
authors.forename: M K
authors.initials: MK
authors.lastname: Unnikrishnan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005215:Fasting / Q000097:blood; D005951:Glucose Tolerance Test; D017127:Glycation End Products, Advanced / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009536:Niacinamide; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D003374:Coumarins; D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D009536:Niacinamide; D013311:Streptozocin; D006003:Glycogen; C030123:coumarin; D003404:Creatinine