Xiao_2021_Biomed.Res.Int_2021_5574207

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-beta production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Abeta (25-35)-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Abeta (25-35)-microinjected rats attenuated hippocampal NF-kappaB activity; inhibited proinflammatory markers, namely, IL-1beta, IL-6, and TNF-alpha; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1beta, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Abeta (25-35)-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Abeta (25-35) through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism.