Hypoglycemic activity of 6-bromoembelin and vilangin in high-fat diet fed-streptozotocin-induced type 2 diabetic rats and molecular docking studies.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Bioinformatics, Entomology Research Institute, Loyola College, Chennai 600034, India.
Antony
A
Stalin
Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
Santiagu Stephen
SS
Irudayaraj
Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
Gopalsamy Rajiv
GR
Gandhi
Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India.
Kedike
K
Balakrishna
Division of Bioinformatics, Entomology Research Institute, Loyola College, Chennai 600034, India; Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600034, India; Visiting professor program, Deanship of Scientific Research, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. Electronic address: eriloyola@hotmail.com.
Savarimuthu
S
Ignacimuthu
Department of Botany and Microbiology, Addiriyah Chair for Environmental Studies, College of Science, King Saud University, Post box 2455, Riyadh 11451, Saudi Arabia.
Naif Abdullah
NA
Al-Dhabi
D000818:Animals; D016227:Benzoquinones / Q000627:therapeutic use*; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D059305:Diet, High-Fat; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D062105:Molecular Docking Simulation; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
C000614453:6-bromoembelin; D016227:Benzoquinones; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; C000614454:vilangin; D013311:Streptozocin
6-Bromoembelin; Biochemical analysis; Molecular-docking; PPARγ; Type 2 diabetes mellitus; Vilangin