Stalin Antony, Irudayaraj Santiagu Stephen, Gandhi Gopalsamy Rajiv, Balakrishna Kedike, Ignacimuthu Savarimuthu, Al-Dhabi Naif Abdullah
Division of Bioinformatics, Entomology Research Institute, Loyola College, Chennai 600034, India.
Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
Life Sci. 2016 May 15;153:100-17. doi: 10.1016/j.lfs.2016.04.016. Epub 2016 Apr 26.
This paper investigates the hypoglycemic activity of two derivatives of embelin (1) viz. 6-bromoembelin (2) and vilangin (3), in high-fat diet - STZ induced diabetic rats.
The effects of 6-bromoembelin (2) and vilangin (3) on insulin resistance, β-cell dysfunction and glucose transport in high-fat diet (HFD) fed-streptozotocin (STZ) (40mg/kg) induced type 2 diabetic rats were evaluated. The binding modes of 6-bromoembelin (2) and vilangin (3) into PPARγ, PI3K, Akt, and GLUT4 were also studied using Autodock 4.2 and ADT 1.5.6 programs.
At the dose of 30mg/kg, the plasma glucose, plasma insulin and body weight were reduced by both embelin derivatives in diabetic rats. Additionally the altered lipid profiles and hexokinase, glucose-6-phosphatase and fructose-1,6-bisphosphatase levels were brought to normal. Compared to diabetic control group, there was a significant increase in the expression of PPARγ in epididymal adipose tissue. Inhibition of adipogenic activity and mild activation of PPARγ levels in the skeletal muscle and liver were observed. In epididymal adipose tissue, the compounds increased the insulin-mediated glucose uptake through the activation and translocation of GLUT4 in PI3K/p-Akt signaling cascade.
The derivatives of embelin such as 6-bromoembelin (2) and vilangin (3) may be useful in the prevention and treatment of obesity-linked type 2 diabetes mellitus.
本文研究了紫铆因（1）的两种衍生物，即6-溴紫铆因（2）和维朗京（3）对高脂饮食 - 链脲佐菌素诱导的糖尿病大鼠的降血糖活性。
评估了6-溴紫铆因（2）和维朗京（3）对高脂饮食（HFD）喂养的链脲佐菌素（STZ）（40mg/kg）诱导的2型糖尿病大鼠胰岛素抵抗、β细胞功能障碍和葡萄糖转运的影响。还使用Autodock 4.2和ADT 1.5.6程序研究了6-溴紫铆因（2）和维朗京（3）与过氧化物酶体增殖物激活受体γ（PPARγ）、磷脂酰肌醇-3激酶（PI3K）、蛋白激酶B（Akt）和葡萄糖转运蛋白4（GLUT4）的结合模式。
在30mg/kg剂量下，两种紫铆因衍生物均可降低糖尿病大鼠的血糖、血浆胰岛素水平和体重。此外，还使改变的血脂谱以及己糖激酶、葡萄糖-6-磷酸酶和果糖-1,6-二磷酸酶水平恢复正常。与糖尿病对照组相比，附睾脂肪组织中PPARγ的表达显著增加。观察到骨骼肌和肝脏中脂肪生成活性受到抑制，PPARγ水平轻度激活。在附睾脂肪组织中，这些化合物通过PI3K/p-Akt信号级联中GLUT4的激活和转位增加了胰岛素介导的葡萄糖摄取。
6-溴紫铆因（2）和维朗京（3）等紫铆因衍生物可能对预防和治疗肥胖相关的2型糖尿病有用。
