7-o-galloyl-d-sedoheptulose and Disease-Models--Animal

Compelling evidence indicates that polyphenolic antioxidants show protective effects against diabetic complications. We investigated the effects of a polyphenolic compound, 7-O-galloyl-D-sedoheptulose (GS), from Corni Fructus on a type 2 diabetic db/db mouse model. After 6 weeks of GS treatment, the effects of GS on serum and pancreatic biochemical factors were investigated. To define the underlying mechanism of these effects, we examined several key inflammatory markers, and inflammation-related oxidative stress markers. The results showed that levels of glucose, leptin, insulin, C-peptide, resistin, tumor necrosis factor-α, and interleukin-6 in serum were down-regulated, while adiponectin was augmented by GS treatment. In addition, GS suppressed reactive oxygen species and lipid peroxidation in the pancreas, but increased the pancreatic insulin and pancreatic C-peptide contents. Moreover, GS modulated protein expressions of pro-inflammatory nuclear factor-kappa Bp 65, cyclooxygenase-2, inducible nitric oxide synthase, c-Jun N-terminal kinase (JNK), phospho-JNK, activator protein-1, transforming growth factor-β1, and fibronectin. Based on these results, we conclude that a plausible mechanism of GS's anti-diabetic action may well be its anti-inflammatory property and anti-inflammatory-related anti-oxidative action. Thus, further investigation of GS as an effective anti-diabetic treatment for type 2 diabetes is warranted.

Topics: Animals; Anti-Inflammatory Agents; Blood Glucose; C-Peptide; Cornus; Cytokines; Diabetes Mellitus, Type 2; Disease Models, Animal; Fibronectins; Heptoses; Hypoglycemic Agents; Insulin; JNK Mitogen-Activated Protein Kinases; Male; Mice; Oxidative Stress; Pancreas; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances; Transcription Factor AP-1

The present study was conducted to examine whether 7-O-galloyl-D-sedoheptulose (GS) has an ameliorative effect on diabetic alterations such as oxidative stress, inflammation, and apoptosis in the liver of type 2 diabetic db/db mice. GS was administered at 20 or 100 mg/kg body weight per day for 6 weeks to db/db mice, and its effect was compared with vehicle-treated db/db and m/m mice. In the serum and hepatic tissue, biochemical factors and protein expressions associated with nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, inflammation, and apoptosis were examined. As a result, GS administration to type 2 diabetic mice lowered serum and hepatic oxidative stress through the reduction of reactive oxygen species and lipid peroxidation. These results were derived, at least in part, from attenuating the expression of NADPH oxidase subunit proteins, Nox-4 and p22(phox). In the diabetic condition, augmented nuclear factor (NF)-E2-related factor 2 and heme oxygenase-1 were reduced with a decrease in oxidative stress on GS treatment. Furthermore, in the GS-treated group, NF-kappa B-related pro-inflammatory factors and pro-apoptotic protein expressions were alleviated in the hepatic tissue. Taking these into consideration, our findings support the therapeutic evidence for GS ameliorating the development of diabetic complications via regulating oxidative stress, inflammation, and apoptosis.

Topics: Animals; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Diabetes Mellitus, Type 2; Disease Models, Animal; Heptoses; Liver Diseases; Male; Mice; NF-kappa B; Oxidative Stress; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances