ABSTRACT
The brain is a vital organ that requires a constant blood supply. Stroke occurs when the blood supply to specific parts of the brain is reduced; diabetes is an autonomous risk factor for stroke. The present study aimed to investigate the potential vascular protective effect of gymnemic acid (GM) by assessing the morphological changes of microvasculature, along with VEGFA and angiopoietin-1 (Ang-1) protein expression in the brains of diabetic rats. Rats were divided into five groups, including control, gymnemic control rats (CGM), rats that were rendered diabetic by single injection of 60 mg/kg streptozotocin (STZ), diabetic rats treated with 400 mg/kg GM (STZ + GM) and diabetic rats treated with 4 mg/kg glibenclamide (GL; STZ + GL). After 8 weeks, brain tissues were collected to examine the three-dimensional morphology of the anterior cerebral arteries by vascular corrosion casting. Western blotting was performed to determine VEGFA and Ang-1 expression. Cerebral arteries, arterioles and capillaries were depicted the diameter, thickness and collagen accumulation of the wall, and the results demonstrated narrow diameters, thickened walls and collagen accumulation in the STZ group. After receiving GM, the histopathological changes were similar to that of the control group. Through vascular corrosion casting and microscopy, signs of vessel restoration and improvement were exhibited by increased diameters, and healthy and nourished arterioles and capillaries following treatment with GM. Furthermore, VEGF expression and Ang-1 secretion decreased in the STZ + GM group compared with STZ rats. The results of the present study revealed that GM treatment decreased blood vessel damage in the brain, suggesting that it may be used as a therapeutic target for the treatment of diabetes.
ABSTRACT
Abnormalities in insulin hormone levels leads to a hyperglycemic condition of diabetic mellitus. Hyperglycemia seriously induces organ and system destructions. The excessive accumulation of collagen fiber deposits occurs in inflammatory and reorganization processes of chronic liver diseases in type I insulin-dependent diabetes. Regarding the research objective, glabridin (GLB), an active compound of licorice, was used as a daily supplement (40 mg/kg) in order to decrease hepatocyte destruction and collagen deposition in liver tissue of diabetic animals induced by streptozotocin. A total of 40 were randomly allocated to five groups (each, n=10), control, control treated with GLB (GLB), diabetic rats (DM) injected with single dose of streptozotocin (60 mg/kg) to induce a diabetic condition, diabetic rats receiving GLB (DM+GLB; 40 mg/kg) and diabetic rats treated with glibenclamide (DM+GL; 4 mg/kg). Characteristic histopathological changes in liver cells and tissues of rats were determined by Masson's trichrome staining and transmission electron microscopy (TEM). Western blotting was used to detect the expression of the key markers, collagen type I and fibronectin proteins. The histological investigation of liver tissue of the DM group revealed that the collagen fiber deposition was increased in the periportal, pericentral and perisinusoidal spaces compared with controls. Hepatocytes appeared as small and fragmented cells in TEM examination. Collagenization of the perisinusoidal space was recently demonstrated to represent a new aspect of the microvascular abnormalities and liver fibrosis. Healthy hepatocytes with round nucleus were observed following supplementation of glabridin. In addition, collagen fiber deposition was reduced in the area adjacent to the perisinusoidal space. The expression of collagen type I and fibronectin decreased strongly following glabridin supplementation in DM+GLB rats compared with DM rats, indicating that the hepatic tissue reorganization regained its normal morphology. These findings suggest that it may be beneficial to examine the role of glabridin as a therapeutic agent in diabetes treatment in future research.
