Anti-diabetic Activity Evaluation Of Two Oxindole Derivatives In Vivo

Oxindole,named indolin-2-one or 1,3-dihydroindol-2-one,is an important pharmacophore in many molecules.These compounds are a kind of high-profile alkaloids that consist of a multifunctional oxindoles which possess broad and significant biological properties,such as antitumor,antibacterial,antinociceptive,antiviral,antitubercular and antihypertensive activity,et al.Rencently,the biological evaluation of oxindole alkaloids have attracted an increasing amount of attention.Our previous study have identified tetracyclic oxindole derivative I and indirubin derivative II exhibiting potent inhibitory activity of a-glucosidase with ICSo= 4.8 μM and 2.8 μM,respectively.Both of two compounds are better than that of acarbose(IC50 ＝51.3 μM),which is a clinic a-glucosidase inhibitor for treatment of diabetes.Therefore,the aim of this study was to investigate whether these two compounds improve hyperglycemia and hyperlipemia in high-fat-fed,STZ-induced type 2 diabetic mice in vivo.Male Kunming mice weighing 18-22 g were induced by intraperitoneal injection of STZ,after 3 weeks of diets high in fat and fructose.The experimental mice of type 2 diabetes models was established by selectively destructed part of the pancreatic cells and induced insulin resistance or relative lack.The anti-hyperglycemia and anti-hyperlipemia of compounds I and II studied with evaluating indicators including food intake,water intake,body weight,blood glucose,serum total cholesterol and triglycerides,and histological changes of organs and tissues.Acarbose was a positive control.The results suggested that two compounds slight differently change in evaluating indicators of food intake,water intake and body weight compared with negative control.However,it can significantly reduce postprandial blood glucose and ameliorate oral glucose tolerance in vivo,and hypoglycemic effect is more obvious than acarbose.In addition,it reduced serum total cholesterol and triglycerides levels,and improved severity STZ-induced fatty liver in diabetic mice.