Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, attenuates diabetes-induced renal damage through the advanced glycation end product-related pathway in db/db mice

J Nutr. 2014 Aug;144(8):1150-7. doi: 10.3945/jn.114.193961. Epub 2014 Jun 11.

Abstract

This study was conducted to examine whether oligonol, a low-molecular-weight polyphenol derived from lychee fruit, has an ameliorative effect on diabetes-induced alterations, such as advanced glycation end product (AGE) formation or apoptosis in the kidneys of db/db mice with type 2 diabetes. Oligonol [10 or 20 mg/(kg body weight · d), orally] was administered every day for 8 wk to prediabetic db/db mice, and its effect was compared with vehicle-treated db/db and normal control mice (m/m). The administration of oligonol decreased the elevated renal glucose concentrations and reactive oxygen species in db/db mice (P < 0.05). The increased serum urea nitrogen and creatinine concentrations, which reflect renal dysfunction in db/db mice, were substantially lowered by oligonol. Oligonol reduced renal protein expression of NAD(P)H oxidase subunits (p22 phagocytic oxidase and NAD(P)H oxidase-4), AGEs (except for pentosidine), and c-Jun N-terminal kinase B-targeting proinflammatory tumor necrosis factor-α (P < 0.05). Oligonol improved the expressions of antiapoptotic [B-cell lymphoma protein 2 (Bcl-2) and survivin] and proapoptotic [Bcl-2-associated X protein, cytochrome c, and caspase-3] proteins in the kidneys of db/db mice (P < 0.05). In conclusion, these results provide important evidence that oligonol exhibits a pleiotropic effect on AGE formation and apoptosis-related variables, representing renoprotective effects against the development of diabetic complications in db/db mice with type 2 diabetes.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Urea Nitrogen
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Creatinine / blood
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / drug therapy
  • Fruit / chemistry
  • Glycation End Products, Advanced / metabolism*
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / physiopathology*
  • Litchi / chemistry*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NADPH Oxidase 4
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism
  • Organ Size / drug effects
  • Oxidative Stress / drug effects
  • Phenols / pharmacology*
  • Plant Extracts / pharmacology*
  • Polyphenols / pharmacology
  • Reactive Oxygen Species / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Survivin
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, mouse
  • Birc5 protein, mouse
  • Glycation End Products, Advanced
  • Inhibitor of Apoptosis Proteins
  • Phenols
  • Plant Extracts
  • Polyphenols
  • Reactive Oxygen Species
  • Repressor Proteins
  • Survivin
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • oligonol
  • Catechin
  • Creatinine
  • NADPH Oxidase 4
  • NADPH Oxidases
  • Nox4 protein, mouse
  • JNK Mitogen-Activated Protein Kinases
  • Casp3 protein, mouse
  • Caspase 3