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.

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.

Background: A high prevalence of atherosclerotic vascular lesions has been associated with renal disease and diabetes and is a major cause for increasing deaths from cardiovascular disease. The present study aimed to determine the beneficial effects of gymnemic acids on the kidney microvasculature and to establish their anti-angiogenic properties that are related to the expression of vascular endothelial growth factor (VEGF) protein of segmental and interlobar arteries in induced diabetic rats. Methods: Rats were divided into five groups including the control group (C), control treated with gymnemic acid (CGM), diabetic animals (DM group) that were rendered diabetic by a single dose [60 mg/kg body weight (BW)] of a streptozotocin (STZ) injection, diabetic rats treated with gymnemic acid (400 mg/kg BW) (GM), and diabetic rats treated with glibenclamide (4 mg/kg BW) (GR). After 8 weeks, kidney tissues were collected for histological analysis. In rats with DM, the segmental arteries exhibited increased wall thickness. The kidney microvasculature was examined using the vascular corrosion casting method. Results: Rats with DM presented a decreasing diameter of segmental and interlobar arteries. They were evidently redeveloped and restored in the GM and GR groups. As determined by immunofluorescence, the expression of VEGF was significantly reduced in both the GM and GR groups. Conclusions: The present study demonstrated that gymnemic acid from Gymnemasylvestre may be a promising medical herb for use in the treatment of diabetes and kidney disease.Keywords: diabetes mellitus, segmental artery, interlobar artery, gymnemic acid, vascular architecture

Calloselasma rhodostoma (Malayan pit viper) is a medically important snake species that is widely distributed across Southeast Asia. Systemic coagulopathy causing severe haemorrhage and local tissue injury is commonly observed following C. rhodostoma envenoming. However, nephrotoxicity and congestive heart failure were previously reported in a patient who had a long length of hospital stay. In this study, we determined the effect of C. rhodostoma envenoming on cardiovascular disturbances and the associated morphological changes in the liver, heart and kidneys using animal models. We also evaluated the efficacy of Hemato polyvalent antivenom (HPAV; Queen Saovabha Memorial Institute (QSMI) of the Thai Red Cross Society, Thailand) in neutralising the histopathological effects of C. rhodostoma venom. The intravenous (i.v.) administration of C. rhodostoma venom (1000 µg/kg) caused a rapid decrease in mean arterial pressure (MAP) followed by complete cardiac collapse in anaesthetized rats. Moreover, the intraperitoneal (i.p.) administration of C. rhodostoma venom (11.1 mg/kg; 3×LD50) for 24 h caused cellular lesions in the liver and heart tissues. C. rhodostoma venom also induced nephrotoxicity, as indicated by the presence of tubular injury, interstitial vascular congestion and inflammatory infiltration in the whole area of the kidney. The administration of HPAV, at manufacturer-recommended doses, 15 min prior to or after the addition of C. rhodostoma venom reduced the extent of the morphological changes in the liver, heart and kidneys. This study found that experimental C. rhodostoma envenoming induced cardiovascular disturbances, hepatotoxicity and nephrotoxicity. We also highlighted the potential broad utility of HPAV to neutralise the histopathological effects of C. rhodostoma venom. The early delivery of antivenom appears capable of preventing envenoming outcomes.

IntroductionThe aim of this study was to investigate the effects of glabridin, on vascular inflammation and vascular remodeling of the left anterior descending artery in diabetic rat heartMaterial and methodsRats were divided into five groups. (1) control rats (C); (2) glabridin control rats (CGB); (3) diabetic rats (STZ); (4) diabetic rats received glabridin (STZ+GB) 40 mg/kg BW and (5) diabetic rats were treated with glyburide (STZ+GR) 4 mg/kg BW. After 8 weeks, the oxidative stress markers were carried out. LAD was examined by vascular corrosion casting. Enzyme-linked immunosorbent assay was applied to determine the expression of VEGF and TGF-β secretions, as well as tumor necrotic factor (TNF-α) and interleukin-1 (IL-1β) proteins.ResultsThe lumen diameter of LAD was notably smaller and presented stenosis. LAD revealed arterial notch and evolved irregular caliber. Moreover, neovascularization emerged and was presented extensively. The Trolox equivalent antioxidant capacities, TEAC levels, of heart tissue were significantly decreased and levels of MDA were found to be elevated in STZ rats whereas they were improved in the STZ+GB group. Increased expressions of VEGF, TGF-β1, TNF-α, and IL-1β proteins in heart tissues were demonstrated in the STZ group. The inflammation cytokines were decreased in the STZ+GB group.ConclusionsThese results revealed that glabridin was able to reduce LAD damage. Glabridin can be an antioxidant and can reduce the pathology of the LAD in terms of reducing inflammation. It would be beneficial in examining the role of glabridin as a therapeutic aim in diabetes treatment research in coronary artery disease (CAD).