Neuroprotective effects of quercetin on memory and anxiogenic-like behavior in diabetic rats: Role of ectonucleotidases and acetylcholinesterase activities

Biomed Pharmacother. 2016 Dec;84:559-568. doi: 10.1016/j.biopha.2016.09.069. Epub 2016 Sep 29.


The present study investigated the protective effect of quercetin (Querc) on memory, anxiety-like behavior and impairment of ectonucleotidases and acetylcholinesterase (AChE) activities in brain of streptozotocin-induced diabetic rats (STZ-diabetes). The type 1 diabetes mellitus was induced by an intraperitoneal injection of 70mg/kg of streptozotocin (STZ), diluted in 0.1M sodium-citrate buffer (pH 4.5). Querc was dissolved in 25% ethanol and administered by gavage at the doses of 5, 25 and 50mg/kg once a day during 40days. The animals were distributed in eight groups of ten animals as follows: vehicle, Querc 5mg/kg, Querc 25mg/kg, Querc 50mg/kg, diabetes, diabetes plus Querc 5mg/kg, diabetes plus Querc 25mg/kg and diabetes plus Querc 50mg/kg. Querc was able to prevent the impairment of memory and the anxiogenic-like behavior induced by STZ-diabetes. In addition, Querc prevents the decrease in the NTPDase and increase in the adenosine deaminase (ADA) activities in SN from cerebral cortex of STZ-diabetes. STZ-diabetes increased the AChE activity in SN from cerebral cortex and hippocampus. Querc 50mg/kg was more effective to prevent the increase in AChE activity in the brain of STZ-diabetes. Querc also prevented an increase in the malondialdehyde levels in all the brain structures. In conclusion, the present findings showed that Querc could prevent the impairment of the enzymes that regulate the purinergic and cholinergic extracellular signaling and improve the memory and anxiety-like behavior induced by STZ-diabetes.

Keywords: Acetylcholinesterase; Anxiety; Diabetes; Ectonucleotidases; Memory; Quercetin.

MeSH terms

  • 5'-Nucleotidase / metabolism*
  • Acetylcholinesterase / metabolism*
  • Adenosine Deaminase / metabolism*
  • Animals
  • Anxiety / chemically induced
  • Anxiety / enzymology
  • Anxiety / prevention & control*
  • Anxiety / psychology
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / physiopathology
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / psychology
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / enzymology
  • Diabetes Mellitus, Type 1 / psychology
  • Dose-Response Relationship, Drug
  • GPI-Linked Proteins / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Memory Disorders / chemically induced
  • Memory Disorders / enzymology
  • Memory Disorders / prevention & control*
  • Memory Disorders / psychology
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Quercetin / pharmacology*
  • Rats, Wistar
  • Streptozocin


  • GPI-Linked Proteins
  • Neuroprotective Agents
  • Malondialdehyde
  • Streptozocin
  • Quercetin
  • Acetylcholinesterase
  • Ache protein, rat
  • 5'-Nucleotidase
  • Nt5e protein, rat
  • Adenosine Deaminase