Rosuvastatin alleviates high-salt and cholesterol diet-induced cognitive impairment in rats via Nrf2-ARE pathway

Redox Rep. 2018 Dec;23(1):168-179. doi: 10.1080/13510002.2018.1492774.


Objective: The objectives of our study were to investigate the possible effect of rosuvastatin in ameliorating high salt and cholesterol diet (HSCD)-induced cognitive impairment and to also investigate its possible action via the Nrf2-ARE pathway.

Methods: In silico studies were performed to check the theoretical binding of rosuvastatin to the Nrf2 target. HSCD was used to induce cognitive impairment in rats and neurobehavioral studies were performed to evaluate the efficacy of rosuvastatin in enhancing cognition. Biochemical analyses were used to estimate changes in oxidative markers. Western blot and immunohistochemical analyses were done to check Nrf2 translocation. TUNEL and caspase 3 tests were performed to evaluate reversal of apoptosis by rosuvastatin.

Results: Rosuvastatin showed good theoretical affinity to Nrf2, significantly reversed changes in oxidative biomarkers which were induced by HSCD, and also improved the performance of rats in the neurobehavioral test. A rise in nuclear translocation of Nrf2 was revealed through immunohistochemical analysis and western blot. TUNEL staining and caspase 3 activity showed attenuation of apoptosis.

Discussion: We have investigated a novel mechanism of action for rosuvastatin (via the Nrf2-ARE pathway) and demonstrated that it has the potential to be used in the treatment of cognitive impairment.

Keywords: Cognitive impairment; Nrf2; high-salt and cholesterol diet; nuclear factor (erythroid-derived 2)-like 2; oxidative stress; rosuvastatin.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects
  • Cholesterol / adverse effects*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Female
  • Glutathione / metabolism
  • Glutathione Disulfide / metabolism
  • Glutathione Peroxidase / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Rosuvastatin Calcium / therapeutic use*
  • Sodium Chloride / toxicity*


  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Sodium Chloride
  • Rosuvastatin Calcium
  • Adenosine Triphosphate
  • Cholesterol
  • Glutathione Peroxidase
  • Glutathione
  • Glutathione Disulfide

Grant support

This work was supported by the Department of Science and Technology Ministry of Science and Technology [Grant number IF130014], Government of India; Science and Engineering Research Board.