Alzheimer's disease (AD) is a chronic, neurodegenerative disorder that affects the central nervous system and is found predominantly in elderly populations. As amyloid b protein (Ab) is one of the key players responsible for the pathogenesis of AD, we sought to investigate the protective effects of fisetin in an Ab1-42-induced rat model of AD. In this model, the protective effects of fisetin on learning and memory impairment induced by Ab1-42 were determined via the Morris water maze and passive avoidance test. Furthermore, the antioxidant activity, anti-inflammation, and apoptosis effect of fisetin were investigated using biochemical and immunohistochemical methods. The results showed that intragastric (i.g.) administration of fisetin (100, 50, and 25 mg/kg) improved previous learning and memory impairments in Ab1-42-treated rats. Hippocampal tissue from these fisetin-treated rats revealed that the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were markedly enhanced, and that the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were significantly reduced. Meanwhile, fisetin also significantly attenuated Ab1-42-induced cholinergic dysfunction such as elevated the activity of choline acetyltransferase (ChAT) and reduced the activity of acetylcholine esterase (AChE). In addition, hippocampal tissue obtained from fisetin-treated rats revealed a reversal of Ab1-42-induced effects on apoptotic pathway protein (caspase-3) expression and inflammatory response of glial fibrillary acidic protein (GFAP). This indicated that the amount of degenerating hippocampal neurons with apoptotic features was dramatically reduced after treatment with fisetin. Collectively, these findings suggest that fisetin has potential as a treatment agent for Alzheimer's disease and that its effects occur through several mechanisms, including inhibition of oxidative stress, adjustments to previous cholinergic dysfunction, anti-inflammatory actions, and decreased apoptotic activity.
Keywords: Ab1-42; fisetin; mechanism; protective effects; Alzheimer's disease.