Polyhydroxy stilbenes have been reported to possess various biological activities, and have potential in the treatment of Alzheimer's disease (AD). Tetrahydroxystilbene glucoside is one of the major polyhydroxy stilbenes, which provides underlying therapeutic activities for neuroprotective actions in various experimental conditions. This study intends to investigate the impact of tetrahydroxystilbene glucoside remedy for cognitive disorder and oxidative stress in Aβ1-42-induced AD mice and to clarify the mechanisms of action through Keap1/Nrf2 pathway. It was found that The swimming time of Aβ1-42-induced mice which were treated by tetrahydroxystilbene glucoside (30, 60 and 120 mg/kg) was significantly increased in the target quadrant through the Morris water maze experiment and the number of avoidances was increased through the passive avoidance experiment. Moreover, tetrahydroxystilbene glucoside attenuated Aβ1-42-induced memory impairment, however, the locomotor and exploratory activity of the mice were not affected. Tetrahydroxystilbene glucoside obviously decreased the levels of MDA and GSSG in both hippocampus and cortex compared with the Aβ1-42-treated group, and obviously increased the level of GSH and activities of CAT and SOD in above tissues. The results of this study also demonstrated that tetrahydroxystilbene glucoside increased Nrf2 and HO-1 protein expression and decreased Keap1 protein expression in a concentration-dependent manner in Aβ1-42-treated mice, which involved in the Keap1/Nrf2 antioxidant pathway in hippocampus and cerebral cortex tissue. These results demonstrated that tetrahydroxystilbene glucoside as a natural drug might provide potential treatment for AD.
Keywords: Alzheimer’s disease; Keap1/Nrf2 pathway; Tetrahydroxystilbene glucoside; oxidative stress; β-amyloid.