Isorhamnetin improves cognitive impairment of Alzheimer’s disease through Sirt1/AKT/ERK/CREB signaling pathway

Abstract Isorhamnetin (IH) is one of a flavonoid with extensive pharmacological activities, including anti-inflammation and antioxidation. Although IH has a protective effect in neurological diseases, its role in Alzheimer's disease (AD) is not very clear. In order to explore the effect and mechanism of IH in AD, 4-month-old APP/PS1mice treated with IH in 50 mg/kg/d for 3 months and Morris water maze and immunofluorescence staining were used to detect whether IH could improve AD pathology. The mechanisms of IH improving AD pathology were detected by Western blot. The results showed that after IH treatment, the time of escape latency was significantly reduced and the number of crossing the platform was significantly increased, suggesting that IH can improve the cognitive impairment of mice. Moreover, IH significantly decreased senile plaques deposition in the brain and increased the expression of ADAM10 in APP/PS1 mice through activating Sirt1/AKT/ERK/CREB pathway. Furthermore, IH reduced ROS formation, GP91 expression, upregulated the expression of SOD1 and Nrf2. Moreover, IH inhibited astrocytes activation and pro-inflammatory cytokine IL-1β and TNF-α release. In conclusion, IH improved cognitive function, inhibited oxidative stress and inflammation response in AD. Therefore, we suggest that IH may be considered as a potential drug for AD treatment.