HO-1 mediated by PI3K/Akt/Nrf2 signaling pathway is involved in (-)-epigallocatechin-3-gallate-rescueing impaired cognitive function induced by chronic cerebral hypoperfusion in rat model

Background Epigallocatechin-3-gallate (EGCG) has neuroprotection on chronic cerebral hypoperfusion (CCH) against oxidative stress. HO-1 may represent a target for treatment with CCH. This study aimed to observe the effect of EGCG on cognition impaired in a rat model with CCH and investigate the mechanism. Methods Sprague-Dawley rat models of CCH were established using the 2-VO procedures. Novel object recognition and Morris water maze tests were determined the effects of EGCG on the impaired cognitive functions; HE staining was for detecting the histopathological changes; oxidative stress was assessed by measuring MDA, SOD levels and HO-1 activity. Western blots were for the expression of HO-1, PI3K, Akt (p-Akt), and Nrf2. Results After EGCG treatment, the rats with CCH by 2-VO spent obviously longer time exploring the novel objects, had significantly shorter escape latency and better spatial exploring ability. Meanwhile, EGCG reduced the histopathological changes. Moreover, EGCG increased the concentration of SOD and the activity of HO-1, but decreased the MDA contents. Furthermore, EGCG treatment induced the expression of PI3K, p-Akt, Nrf2, and HO-1 protein, and they were partly reversed by the LY294002, siRNA-Nrf2, or ZnPP. Conclusions EGCG has a neuroprotective effect on rat impaired cognition induced by CCH, possibly by modulating the PI3K/AKT/Nrf2/HO-1 pathway.