Celastrol Attenuates Learning and Memory Deficits in an Alzheimer's Disease Rat Model.

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 Hook F that has been shown to enhance cell viability and inhibit amyloid- production induced by lipopolysaccharides . In the present study, the protective effect of CEL on A -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 A -microinjected rats attenuated hippocampal NF-B activity; inhibited proinflammatory markers, namely, IL-1, IL-6, and TNF-; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in A -microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal A through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism.