Abstract: AimTo explore the effect and the possible mechanism of ginsenoside Rb1 on β-amyloid peptide (β-AP)_25-35-induced tau protein hyperphosphorylation in cortical neurons. MethodsWestern blotting and immunocytochemical staining were used to detect tau phosphorylation level，total tau and glycogen synthase kinase-3β (GSK-3β) in cortical neurons. ResultsAfter exposure to β-AP_25-35 (20 μmol·L^-1) for 12 h, the levels of tau protein phosphorylation in the sites of Ser 396, Ser 199/202, Thr 231 and total tau were raised. Meanwhile, the expression of GSK-3β also increased. Pretreatment with ginsenoside Rb1 or lithium chloride, a specific inhibitor of GSK-3β, markedly reduced β-AP_25-35-induced tau hyperphosphorylation and the expression of GSK-3β. ConclusionGinsenoside Rb1 can attenuate β-AP_25-35-induced tau protein hyperphosphorylation in cortical neurons by inhibiting the expression of GSK-3β.