Protective Effect of Proanthocyanidin against Diabetic Oxidative Stress.

We investigated the antidiabetic potential of proanthocyanidin and its oligomeric form in STZ-induced diabetic model rats and db/db type 2 diabetic mice. Proanthocyanidin ameliorated the diabetic condition by significant decreases of serum glucose, glycosylated protein, and serum urea nitrogen as well as decreases of urinary protein and renal-AGE in STZ-induced diabetic rats and decrease of serum glucose as well as significant decrease of glycosylated protein in db/db type 2 diabetic mice. The suppression of ROS generation and elevation of the GSH/GSSG ratio were also observed in the groups administered proanthocyanidin. Moreover, proanthocyanidin, especially its oligomeric form, affected the inflammatory process with the regulation of related protein expression, iNOS, COX-2 and upstream regulators, NF-κB, and the IκB-α. In addition, it had a marked effect on hyperlipidemia through lowering significant levels of triglycerides, total cholesterol, and NEFA. Moreover, expressions in the liver of SREBP-1 and SREBP-2 were downregulated by the administration of proanthocyanidins. The protective effect against hyperglycemia and hyperlipidemia in type 1 and 2 diabetic models was significantly strong in the groups administered the oligomeric rather than polymeric form. This suggests that oligomers act as a regulator in inflammatory reactions caused by oxidative stress in diabetes.