The Effect of Kaempferol on Autophagy and Nrf-۲ Signaling in a Rat Model of Aβ۱-۴۲-induced Alzheimer’s Disease

Background: Numerous pieces of evidence support that oxidative stress is a key factor in the pathogenesis of neurodegenerative diseases, like Alzheimer’s Disease (AD). Suppression of oxidative stress is an attractive strategy and flavonoids as potent natural antioxidants are extremely noticeable.  Objectives: In this study, the effects of Kaempferol (KMP) were evaluated on passive avoidance memory, hippocampal Nrf-۲, and beclin-۱ expression in a rat model of Aβ۱-۴۲ –induced AD. Materials & Methods: Forty male Wistar rats weighing ۲۰۰-۲۵۰ g were divided into five groups (n=۸); sham-operated, AD model, and KMP treatment (۵, ۷.۵, ۱۰ mg/kg, i.p. for three weeks). Animals received an intracerebroventricular injection of amyloid-beta (۱-۴۲) to establish an AD model. Passive avoidance memory of rats was evaluated using a shuttle box on day ۲۱; Step-Through Latency (STL) and time spent in The Dark Compartment (TDC) were recorded. Then, hippocampus homogenates were used for biochemical and molecular analysis by real-time PCR, western blot, and ELISA. Results: It was found that KMP improved memory evidenced by increased STL (P≤۰.۰۵) and decreased TDC (p≤۰.۰۱). KMP also increased the levels of Total Antioxidant Capacity (TAC) in the hippocampus of rats (P≤۰.۰۵). In addition, KMP enhanced the expression of Nrf-۲ mRNA (P≤۰.۰۰۱) and beclin-۱ protein in the hippocampus tissues (P≤۰.۰۰۱). Conclusion: Overall, it is suggested that the memory-improving effect of KMP is mediated, at least in part, by enhancing Nrf-۲ and TAC. KMP is also able to induce autophagy through the expression of beclin-۱.

Keywords:

Alzheimer’s disease , autophagy , Nrf-۲ and , Kaempferol