a Department of Pharmacology, School of Pharmaceutical Education and Research , Jamia Hamdard (Hamdard University) , New Delhi , India.
b Department of Biotechnology, School of Chemical and Life Sciences , Jamia Hamdard (Hamdard University) , New Delhi , India.
Redox Rep. 2018 Dec;23(1):168-179. doi: 10.1080/13510002.2018.1492774.
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.
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.
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.
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.
本研究旨在探讨瑞舒伐他汀对高盐和胆固醇饮食（HSCD）诱导的认知障碍的可能改善作用，并通过 Nrf2-ARE 通路探讨其可能的作用机制。
通过计算机模拟研究来检查瑞舒伐他汀与 Nrf2 靶标的理论结合情况。使用 HSCD 诱导大鼠认知障碍，并进行神经行为学研究以评估瑞舒伐他汀增强认知的功效。采用生化分析来评估氧化标志物的变化。进行 Western blot 和免疫组化分析以检查 Nrf2 易位。通过 TUNEL 和 caspase 3 试验评估瑞舒伐他汀对细胞凋亡的逆转作用。
瑞舒伐他汀与 Nrf2 具有良好的理论亲和力，可显著逆转 HSCD 诱导的氧化生物标志物的变化，并改善大鼠在神经行为学测试中的表现。免疫组化分析和 Western blot 显示 Nrf2 的核易位增加。TUNEL 染色和 caspase 3 活性显示细胞凋亡减弱。
我们研究了瑞舒伐他汀的一种新作用机制（通过 Nrf2-ARE 通路），并证明它有可能用于治疗认知障碍。
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