Effects of proanthocyanidin preparations on hyperlipidemia and other biomarkers in mouse model of type 2 diabetes

J Agric Food Chem. 2008 Sep 10;56(17):7781-9. doi: 10.1021/jf800639m. Epub 2008 Aug 9.

Abstract

The protective effect of proanthocyanidins from persimmon peel, using both oligomers and polymers, was investigated in a db/db type 2 diabetes model. Male db/db mice were divided into three groups: control (vehicle), polymer-, or oligomer- (10 mg/(kg body weight x day x p.o.)) administered mice. Age-matched nondiabetic m/m mice were used as a normal group. The administration of proanthocyanidins reduced hyperglycemia in db/db mice through a decline in the serum level of glucose and glycosylated protein. In addition, it had a strong effect on hyperlipidemia through lowering levels of triglyceride, total cholesterol, and nonesterified fatty acids. The protective effect against hyperglycemia and hyperlipidemia was greater in the groups administered the oligomeric rather than polymeric form. The increased oxidative stress in db/db mice was attenuated by the administration of oligomers through inhibiting the generation of reactive oxygen species and lipid peroxidation and elevating the reduced glutathione/oxidized glutathione ratio. On the other hand, polymers did not show such an effect. Moreover, expressions in the liver of sterol regulatory element binding protein (SREBP)-1 and SREBP-2 were downregulated by the administration of proanthocyanidins, especially the oligomeric form. Oligomers caused a slight elevation in the expression of peroxisome proliferator-activated receptors alpha. Furthermore, oligomeric proanthocyanidin regulated the expression of nuclear factor kappaB in db/db type 2 diabetes via the activation of inhibitor protein kappaB-alpha. It also attenuated the protein expressions of cyclooxygenase-2 and inducible nitric oxide synthase. This suggests that oligomers would act as a regulator in inflammatory reactions associated with oxidative stress in type 2 diabetes. The present study results suggest that proanthocyanidin administration, especially the oligomeric form, may improve oxidative stress via the regulation of hyperlipidemia than hyperglycemia in type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholesterol / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Hyperglycemia / drug therapy
  • Hyperlipidemias / drug therapy*
  • Lipids / analysis
  • Liver / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR alpha / analysis
  • Proanthocyanidins / administration & dosage*
  • Sterol Regulatory Element Binding Protein 1 / analysis
  • Sterol Regulatory Element Binding Protein 2 / analysis
  • Triglycerides / blood

Substances

  • Lipids
  • PPAR alpha
  • Proanthocyanidins
  • Srebf1 protein, mouse
  • Srebf2 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2
  • Triglycerides
  • proanthocyanidin
  • Cholesterol