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.

目的：我们的研究目的是研究瑞舒伐他汀在减轻高盐和胆固醇饮食（HSCD）引起的认知障碍中的可能作用，并通过Nrf2-ARE途径研究其可能的作用。

方法： 进行计算机研究以检查罗苏伐他汀与Nrf2靶标的理论结合。用HSCD诱导大鼠认知障碍，并进行了神经行为研究以评估瑞舒伐他汀在增强认知方面的功效。生化分析用于估计氧化标记的变化。进行了蛋白质印迹和免疫组化分析以检查Nrf2易位。进行TUNEL和caspase 3测试以评估瑞舒伐他汀逆转凋亡。

结果：瑞舒伐他汀对Nrf2具有良好的理论亲和力，可显着逆转HSCD诱导的氧化生物标志物的变化，并改善了大鼠在神经行为测试中的性能。通过免疫组化分析和免疫印迹揭示了Nrf2核易位的上升。TUNEL染色和caspase 3活性显示出凋亡的减弱。

讨论：我们研究了瑞舒伐他汀（通过Nrf2–ARE途径）的新作用机制，并证明了其有潜力用于治疗认知障碍。