Background: Berberine(BBR)plays an important role in the prevention and treatment of Alzheimers disease(AD).The present work was to explore whether BBR ameliorates cognitive deficits in AD and to investigate whether its underlying mechanism is involved in inhibiting hyperphosphorylated tau protein.Methods: The cognitive function was measured by the Morris water maze(MWM)test.The levels of hyperphosphorylated tau proteins were determined by Western blot.The biomarkers of NF-κB signaling pathway and oxidative stress were detected by Western blot and biochemical assay.The biomarkers of neuroinflammation were determined by Western blot and immunohistochemistry.Results: BBR improved learning and memory in APP/PS1 mice.BBR decreased the hyperphosphorylated tau protein in the hippocampus of APP/PS1 mice.BBR lowered the activity of NF-κB signaling in the hippocampus of AD mice.BBR-administration promoted the activity of glutathione(GSH)and inhibited lipid peroxidation in the hippocampus of AD mice.Conclusion: BBR improved cognitive deficits and limited hyperphosphorylation of tau via inhibiting the activation of NF-κB signaling pathway,and retarding oxidative stress and neuro-inflammation.