Oligonol was orally administered
at 10 or 20 mg/kg
body weight per d for 8 weeks to db/db mice with
type 2 diabetes, and its effects were compared with those of the vehicle in db/db and m/m (misty, non-diabetic) mice. Serum and renal biochemical factors,
protein expressions related to lipid metabolism and
inflammation, and
advanced glycation endproducts were measured. There were significant reductions in the serum
lipid concentration,
reactive oxygen species (ROS) and lipid peroxidation, as well as improvements in renal function parameters. In addition,
oligonol treatment significantly decreased ROS levels and lipid peroxidation in the kidney. In particular, the renal
lipid contents such as TAG and total
cholesterol were significantly reduced in the
oligonol-administered groups through the up-regulation of PPARα and down-regulation of
sterol regulatory
element-binding protein-1 in db/db mice. Moreover,
oligonol inhibited non-fluorescent AGE formation and their receptor expression, suggesting that it could effectively inhibit AGE development caused by oxidative stress and/or dyslipidaemia in the kidney of db/db mice. Furthermore, augmented expressions of NF-κBp65, cyclo-oxygenase-2 and inducible
NO synthase were down-regulated to the levels of m/m mice in the group given
oligonol at 20 mg/kg. This means that
oligonol would act as a regulator in the inflammatory response of
type 2 diabetes. The present results suggest that
oligonol could have renoprotective effects against abnormal lipid metabolism and ROS-related AGE formation in
type 2 diabetes.