Research ReportTetrandrine attenuates spatial memory impairment and hippocampal neuroinflammation via inhibiting NF-κB activation in a rat model of Alzheimer's disease induced by amyloid-β(1-42)

Background: The neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of nuclear factor-κB (NF-κB) activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of AD. Materials and methods: Tetrandrine was administered in a rat model of AD induced by amyloid-β (Aβ)(1-42). The learning and memory impairment was examined using Morris water maze; the extent of histological injury in hippocampus was determined by Nissl staining; NF-κB DNA binding activity was assessed by electrophoretic mobility shift assay; the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β was measured by enzyme-linked immunosorbent assay. Results: A significant improvement was observed in learning and memory impairment in rats with tetrandrine, and the increase in NF-κB DNA binding activity, the over-expression in IL-1β and TNF-α as well as the increased histological injury in hippocampus in rats induced by Aβ(1-42) were significantly reduced following administration of tetrandrine. Conclusion: Tetrandrine could significantly ameliorate Aβ(1-42)-induced spatial learning and memory impairment, and the beneficial effect of tetrandrine treatment could be linked, at least in part, to the inhibition of NF-κB activity and the downregulation of expression of IL-1β and TNF-α, suggesting that administration of tetrandrine may provide a therapeutic approach for AD.

Research highlights► Tetrandrine could ameliorate Aβ(1-42)-induced behavioral impairment. ► Tetrandrine could inhibit Aβ(1-42)-induced neuroinflammation. ► Tetrandrine may be a new therapeutic agent for Alzheimer's disease.