In vivo antidiabetic activity and in silico studies on adenosine monophosphate-activated protein kinase (AMPK) of (2 E ,
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Med Chem Res (2013) 22:2430–2436 DOI 10.1007/s00044-012-0237-1
ORIGINAL RESEARCH
In vivo antidiabetic activity and in silico studies on adenosine monophosphate-activated protein kinase (AMPK) of (2E,5E)-2,5bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone Chenna Govindaraju Darshan Raj • Balladka Kunhanna Sarojini Mahmud Tareq Hassan Khan • Ramappa Raghavendra
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Received: 22 March 2012 / Accepted: 13 September 2012 / Published online: 6 October 2012 Ó Springer Science+Business Media New York 2012
Abstract Effect of bischalcone derivative (2E,5E)-2,5bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone (CA) on blood glucose level and lipid profile was investigated in normoglycemic and streptozotocin (STZ)-induced diabetic rats. In oral glucose and sucrose tolerance test, treatment with CA (25 mg/kg) and glidenclamide (10 mg/kg) significantly improved the glucose and sucrose tolerance in normal animals. In addition, respective treatment for 7-day resulted in significant percentage reduction in serum glucose (SG). In standardized STZ-induced diabetic rats, a single dose of CA treatment exhibited reduction in SG levels at different time intervals compared to basal levels. The lipid profile levels are restored to near-normal value of all tested parameters. The compound CA was docked into the active site of 50 -AMP (adenosine monophosphate)activated protein kinase (PDB ID: 2OOX). The binding and docking energy were found to be -6.9 and -45.1 kcal/mol, respectively. Keywords Bischalcone derivative AMPK Antidiabetes Antihyperglycemic
C. G. D. Raj B. K. Sarojini (&) Department of Chemistry, P.A. College of Engineering, Nadupadavu, Mangalore 574153, Karnataka, India e-mail: [email protected]; [email protected] M. T. H. Khan Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL, USA e-mail: [email protected]; [email protected] R. Raghavendra Department of P.G. Studies and Research in Biochemistry, Kuvempu University, Jnana Sahyadri, Shankaraghatta 577451, Karnataka, India
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Introduction Diabetes is a disorder in which homeostasis of carbohydrate and lipid metabolism is improperly regulated by insulin. This results primarily in elevated fasting and postprandial blood glucose levels. If this imbalanced homeostasis does not return to normalcy and continues for a protracted period of time, it leads to hyperglycemia that in due to course turns into a syndrome called diabetes mellitus (Lernmark and Ott, 1998). The global prevalence of diabetes is estimated to be 2.8 % in 2000 and 4.4 % in 2030. The total number of diabetes is projected to rising from 171 million in 2000 to 366 million in 2030. Medication often has an important role to play particularly for the control of blood glucose and lipids profiles (Wild et al., 2004). External insulin preparations can be used to treat type 1 diabetes mellitus as well as in controlled type 2 diabetes mellitus (T2DM) conditions. The oral hypoglycemic agents such as sulfonylureas (tolbutamide and glibenclamide), Biguanides (phenformin
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