Pterostilbene Alleviates Aβ1‐42‐Induced Cognitive Dysfunction via Inhibition of Oxidative Stress by Activating Nrf2 Signaling Pathway

Scope In the present study, effect of pterostilbene on β‐amyloid 1‐42 (Aβ 1‐42 ) induced cognitive impairment in mice is investigated and explored its possible mechanism of action. Methods and results The behavior results show that pterostilbene alleviated Aβ 1‐42 ‐induces cognitive dysfunction assessed using the Y‐maze test, novel object recognition task, Morris water maze test, and passive avoidance test. Pterostilbene alleviates neuron loss and accumulation of reactive oxygen species in Aβ 1‐42 treated mouse brain. Additionally, pterostilbene promotes nuclear factor‐E2 p45‐related factor 2 (Nrf2) nuclear translocation and enhance the transcription and expression of antioxidant genes such as heme oxygenase‐1 and superoxide dismutase both in vivo and in vitro. Nrf2 inhibitor ML385 reverses the antioxidant function of pterostilbene in SH‐SY5Y cells. Nrf2 is the master regulator of oxidative homeostasis and can be activated by substrate adaptor sequestosome‐1 (also named p62). Pterostilbene promotes the binding of Kelch‐like ECH‐associated protein 1 and p62, which enhanced activation of Nrf2. Conclusion The present study reports that pterostilbene alleviated Aβ 1‐42 ‐induces cognitive dysfunction in mice. The mechanism of pterostilbene can be associated to the inhibition of oxidative stress through the Nrf2 signaling pathway.