Participation of antioxidant and cholinergic system in protective effect of naringenin against type-2 diabetes-induced memory dysfunction in rats

Neuroscience. 2012 Dec 13:226:62-72. doi: 10.1016/j.neuroscience.2012.09.026. Epub 2012 Sep 19.

Abstract

Naringenin is a flavone flavonoid possessing antidiabetic, antioxidant and memory improving effects. Therefore, we studied the influence of naringenin against type-2 diabetes-induced memory dysfunction in rats. Type-2 diabetes was induced by high-fat diet and high-fat emulsion for two weeks and a low dose of streptozotocin (35 mg/kg). The memory deficit was assessed by using a novel object recognition paradigm. The changes in oxidative markers and cholinesterase (ChE) levels were evaluated in the hippocampal region. After confirmation of diabetes, naringenin (50mg/kg) treatment was given to animals as a preventive and in another set of experiments naringenin (25 and 50mg/kg) or pioglitazone (5mg/kg) or donepezil (3mg/kg) treatments were started after long-standing diabetes (4 weeks after confirmation). Both the treatment schedules show significant protection and improvement in cognitive behavior against diabetes-induced memory dysfunction and biochemical changes. Also, treatment with pioglitazone and donepezil improved memory performance in rats. Naringenin was found to decrease oxidative stress by depleting elevated lipid peroxide and nitric oxide and elevating reduced glutathione levels. Cholinergic function was improved by naringenin through the inhibition of elevated ChE activity. In conclusion, the present study suggests that naringenin acts as an antioxidant and ChE inhibitor against type-2 diabetes-induced memory dysfunction.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Cholinesterase Inhibitors / pharmacology
  • Cholinesterases / metabolism
  • Diabetes Mellitus, Experimental / psychology
  • Diabetes Mellitus, Type 2 / psychology*
  • Dietary Fats / pharmacology
  • Donepezil
  • Estrogen Antagonists / pharmacology*
  • Fat Emulsions, Intravenous / pharmacology
  • Flavanones / pharmacology*
  • Glutathione / metabolism
  • Hypoglycemic Agents / pharmacology
  • Indans / pharmacology
  • Lipid Peroxidation / drug effects
  • Male
  • Memory Disorders / etiology*
  • Memory Disorders / prevention & control*
  • Nitric Oxide / metabolism
  • Parasympathetic Nervous System / physiology*
  • Pioglitazone
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Recognition, Psychology / drug effects
  • Thiazolidinediones / pharmacology

Substances

  • Antioxidants
  • Blood Glucose
  • Cholinesterase Inhibitors
  • Dietary Fats
  • Estrogen Antagonists
  • Fat Emulsions, Intravenous
  • Flavanones
  • Hypoglycemic Agents
  • Indans
  • Piperidines
  • Thiazolidinediones
  • Nitric Oxide
  • Donepezil
  • Cholinesterases
  • Glutathione
  • naringenin
  • Pioglitazone