β-Amyloid (Aβ)-mediated neurotoxicity plays a critical role in the pathogenesis of Alzheimer's disease (AD), possibly including Aβ-induced mitochondrial dysfunction and oxidative stress. Previous studies have demonstrated that orientin (Ori) possesses antioxidation capabilities in vitro. Therefore, current study is to demonstrate that Ori can activate Nrf2/HO-1 signaling and alleviate apoptosis induced by Aβ1–42, and ameliorate cognitive deficits in AD mice.Main methods
AD models were made by injecting Aβ1–42 into the bilateral hippocampus of mice. The mice were randomly assigned to three groups: the normal mice and Aβ1–42-induced AD mice with saline, and Aβ1–42-induced AD mice with Ori (5 mg/kg), and were injected intraperitoneally once a day for 15 days. After the Morris Water Maze (MWM) test, mice were sacrificed and brains were harvested for biochemical analysis.Key findings
Results indicated that Ori could ameliorate cognitive deficits in AD mice. Levels of oxidative stress, indicated by production of reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), 4-hydroxy-nonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), were significantly decreased after Ori treatment. In addition, the current study showed that Ori could attenuate mitochondrial dysfunction induced by Aβ1–42, and subsequently inhibited the mitochondrial apoptotic pathway. Ori induced the nuclear translocation of Nrf2, which enhanced the expression of HO-1 and activation of the redox signaling pathway.Significance
Ori might alleviate cognitive deficits and oxidative stress in AD mice, which might be a potential therapeutic drug for AD.