obtusifolin and Hyperglycemia

DM is often accompanied by macrovascular complications. Obtusifolin, which is an anthraquinone‑based compound with antioxidant activity, is obtained from the seeds of Cassia obtusifolia. In this study, the potential effect of obtusifolin was investigated in human umbilical vein endothelial cells. The results from flow cytometry analysis revealed that pretreatment with obtusifolin depressed the production of cellular reactive oxygen species that was induced by high glucose content. Moreover, the results showed that pretreatment with obtusifolin reduced the level of malondialdehyde, as well as recovered the activities of mitochondrial complex I/III, catalase and superoxide dismutase. Furthermore, flow cytometry analysis also revealed that mitochondrial membrane potential and cell apoptosis were recovered, and inhibited by obtusifolin, respectively. The expression of X chromosome‑linked IAP was upregulated, whereas the expressions of poly ADP‑ribose polymerase and cysteinyl aspartate specific proteinase‑3/9 were downregulated by the pretreatment with obtusifolin. Notably, the western blot analyses showed that the release of Omi/HtrA2 into the cytosol was prevented by the pretreatment with obtusifolin. Conclusively, it was suggested that obtusifolin may provide protection against mitochondrial apoptosis largely through inhibition of the release of Omi/HtrA2 from mitochondria into cytosol.

Topics: Anthraquinones; Apoptosis; Cell Survival; Cells, Cultured; Glucose; High-Temperature Requirement A Serine Peptidase 2; Human Umbilical Vein Endothelial Cells; Humans; Hyperglycemia; Membrane Potential, Mitochondrial; Mitochondria; Oxidative Stress; Protective Agents; Reactive Oxygen Species

Oxidative stress is increased in the retina in diabetes, and it is considered to play an important role in the development of retinopathy. Findings indicate that obtusifolin has antioxidant properties. The purpose of this study was to examine the effect of obtusifolin on retinal capillary cell apoptosis and the development of pathology in diabetes. Retina was used from streptozotocin-induced diabetic rats receiving diets supplemented with or without obtusifolin (100, 200, and 400 mg/kg) for 11 months of diabetes. Capillary cell apoptosis (by terminal transferase-mediated dUTP nick-end labeling) and formation of acellular capillaries were investigated in the trypsin-digested retinal microvessels. The effect of obtusifolin administration on retinal 8-hydroxy-2'deoxyguanosine (8-OHdG) and nitrotyrosine levels was determined by enzyme-linked immunosorbent assay. Obtusifolin administration for the entire duration of diabetes inhibited capillary cell apoptosis and the number of acellular capillaries in the retina, despite similar severity of hyperglycemia in the four diabetic groups (with and without obtusifolin). Retinal 8-OHdG and nitrotyrosine levels were significantly increased, respectively, in diabetes, and obtusifolin administration inhibited these increases. Our results demonstrate that the long-term administration of obtusifolin has beneficial effects on the development of diabetic retinopathy via inhibition of accumulation of oxidatively modified DNA and nitrotyrosine in the retina. Obtusifolin represents an achievable adjunct therapy to help prevent vision loss in diabetic patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Administration, Oral; Animals; Anthraquinones; Antioxidants; Apoptosis; Capillaries; Deoxyguanosine; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Hyperglycemia; Male; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar; Retina; Tyrosine