Pterostilbene alleviates Aβ 1-42 -induced cognitive dysfunction via inhibition of oxidative stress by activating Nrf2 signaling pathway

Scope In the present study, we investigated effect of pterostilbene on Aβ1-42 induced cognitive impairment in mice and explored its possible mechanism of action. Methods and results The behavior results showed that pterostilbene alleviated Aβ1-42 -induced cognitive dysfunction assessed using the Y-maze test, novel object recognition task, Morris water maze test, and passive avoidance test. Pterostilbene alleviated neuron loss and accumulation of reactive oxygen species (ROS) in Aβ1-42 treated mouse brain. Additionally, pterostilbene promoted Nrf2 nuclear translocation and enhanced the transcription and expression of antioxidant genes such as HO-1 and SOD both in vivo and in vitro. Nrf2 inhibitor ML385 reversed the antioxidant function of pterostilbene in SH-SY5Y cells. Nrf2 is the master regulator of oxidative homeostasis and can be activated by p62. Pterostilbene promoted the binding of Keap1 and p62 which enhanced activation of Nrf2. Conclusion The present study reported that pterostilbene alleviated Aβ1-42 -induced cognitive dysfunction in mice. The mechanism of pterostilbene can be associated to the inhibition of oxidative stress through the Nrf2 signaling pathway. This article is protected by copyright. All rights reserved.