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 beta-amyloid 1-42 (A beta(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 A beta(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 A beta(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 A beta(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.

Automated summary

Pterostilbene alleviates Aβ(1-42)-induced cognitive dysfunction in mice possibly by inhibiting oxidative stress through the Nrf2 signaling pathway.