7-O-galloyl-D-sedoheptulose ameliorates renal damage triggered by reactive oxygen species-sensitive pathway of inflammation and apoptosis

J Pharm Pharmacol. 2012 Dec;64(12):1730-40. doi: 10.1111/j.2042-7158.2012.01559.x. Epub 2012 Aug 5.

Abstract

Objectives: This study was carried out to verify the preventive effects of 7-O-galloyl-d-sedoheptulose (GS), a phenolic compound isolated from Corni Fructus, underlying diabetic renal damage in type 2 diabetes.

Methods: GS was orally administered to db/db mice at doses of 20 and 100 mg/kg body weight per day for six weeks, and its effects were compared with those of the vehicle in db/db and m/m mice.

Key findings: In the serum and kidney, biochemical factors and expression of protein related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, apoptosis and inflammation were examined. GS treatment attenuated serum and renal oxidative stress through reduction of reactive oxygen species and lipid peroxidation and increase in the ratio of glutathione and its oxidised form. Importantly, GS reduced renal protein expression of Nox-4 and p22(phox) (one of the subunits of NADPH oxidase), pro-apoptotic factors (such as Bax and cytochrome c) and nuclear factor-kappa B-targeting pro-inflammatory inducible nitric oxide synthase and cyclooxygenase-2.

Conclusions: These renoprotective effects of GS were achieved through attenuation of diabetes-induced oxidative stress and its sensitive protein expression associated with inflammation and apoptosis in db/db mice.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cornus / chemistry*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / prevention & control*
  • Glutathione / metabolism
  • Heptoses / isolation & purification
  • Heptoses / pharmacology
  • Heptoses / therapeutic use*
  • Inflammation / blood
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Inflammation Mediators / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NADPH Oxidase 4
  • NADPH Oxidases / blood
  • NADPH Oxidases / metabolism
  • Oxidative Stress / drug effects
  • Phenols / isolation & purification
  • Phenols / pharmacology
  • Phenols / therapeutic use
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Reactive Oxygen Species / metabolism*

Substances

  • 7-O-galloyl-D-sedoheptulose
  • Anti-Inflammatory Agents
  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Heptoses
  • Inflammation Mediators
  • Phenols
  • Plant Extracts
  • Reactive Oxygen Species
  • NADPH Oxidase 4
  • NADPH Oxidases
  • Nox4 protein, mouse
  • Glutathione