Nayak Yogendra, Hillemane Venkatachalam, Daroji Vijay Kumar, Jayashree B S, Unnikrishnan M K
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India.
Department of Chemistry, Kasturba Medical College International Centre, Manipal University, Manipal, Karnataka 576104, India.
ScientificWorldJournal. 2014;2014:854267. doi: 10.1155/2014/854267. Epub 2014 Dec 4.
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.
苯并吡喃酮是糖尿病药物研发中经证实的抗糖尿病药物候选物。基于此观点，选择了新型合成苯并吡喃酮类似物用于实验性糖尿病测试。通过腹腔注射链脲佐菌素（60mg/kg），随后腹腔注射烟酰胺（120mg/kg），在Wistar大鼠中诱导2型糖尿病（T2D）。在T2D诱导7天后，选择空腹血糖（FBG）>200mg/dL的大鼠进行研究。测试化合物和标准治疗持续15天。在T2D诱导后第21天测定FBG、口服葡萄糖耐量试验（OGTT）和胰岛素耐量试验（ITT）。评估血浆脂质和血清胰岛素。然后根据血清胰岛素计算稳态模型评估（HOMA-IR）。处死大鼠并分离胰腺进行组织病理学观察。在肝脏匀浆中评估氧化应激标志物。具有苯并吡喃酮环的天然产物槲皮素显示出与格列本脲相当的显著降血糖活性。与格列本脲相比，测试化合物治疗可降低FBG，并且通过OGTT、HOMA-IR和ITT确定胰岛素抵抗得到显著缓解。与糖尿病大鼠相比，肝脏抗氧化酶有显著恢复正常，表明所有合成的苯并吡喃酮类似物在减轻氧化应激方面有益，并且在实验性T2D中与标准槲皮素和格列本脲相当。
