Pterostilbene Alleviates Aβ 1‐42 ‐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 (Aβ1-42 ) induced cognitive impairment in mice is investigated and explored its possible mechanism of action. METHODS AND RESULTS The behavior results show that pterostilbene alleviated Aβ1-42 -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 Aβ1-42 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 Aβ1-42 -induces cognitive dysfunction in mice. The mechanism of pterostilbene can be associated to the inhibition of oxidative stress through the Nrf2 signaling pathway.