Objective: To investigate the effects of Scutellariabarbata flavonoids (SBF) on abnormal changes of N2a cell protein kinase (PKA) and Tau protein phosphorylation induced by β-amyloid25-35 (Aβ25-35). Methods: N2a cells were cultured and randomly divided into 7 groups, including control group, PKA inhibitor H-89 group, model group, Aβ25-35+H-89 group and SBF three dose treatment groups. The control group was not treated. H-89 with a final concentration of 48 nmol /L was added to the H-89 group, and fully act for 12 h. Aβ25-35 of 40 µmol/L was added to the model group, and work for 12 h. SBF of 1.125 mg/L, 2.25 mg/L and 4.5 mg/L were added to SBF dose treatment groups respectively, and H-89 of 48 nmol /L was added at the same time, after acting cells for 12 h, Aβ25-35 with a final concentration of 40 µmol/L was added to continue the action for 12 h. Western blot was used to detect the phosphorylation expression levels of PKA and Tau protein at Ser199, Ser214, Ser404 and Thr231 of N2a cells to each group. Results: Compared with the control group, the protein expression levels of PKA, p-Tau (Ser199), p-Tau (Ser214), p-Tau (Ser404) and p-Tau (Thr231) were significantly increased in the model group (p< 0.01).In the H-89 group, except for the decreased protein expression levels of PKA, the phosphorylated Tau protein expression levels at Ser199, Ser214, Ser404 and Thr231 of four sites were increased(p< 0.01). Compared with the model group, protein expression levels of PKA, p-Tau (Ser199) and p-Tau (Ser404) in Aβ25-35+H-89 group were significantly decreased (P < 0.01), as well as the phosphorylated Tau expression levels at Ser214 and Thr231 sites (P < 0.05). Compared with group Aβ25-35+H-89, the protein expression levels of p-Tau (Ser404), p-Tau (Ser199), p-Tau (Ser214) and p-Tau (Thr231) were all decreased in the SBF lowdose treatment group, but the protein expression levels of p-Tau (Ser404) were increased. In the SBF medium dose treatment group, the protein expression levels of PKAand p-Tau (Thr231) were increased, while the phosphorylated Tau protein expression levels at Ser199, Ser404 and Ser214 sites were decreased. The expression levels of phosphorylated Tau protein at Ser214 and Ser404 sites were decreased in the SBF highdose group, while the protein express levels of PKA, p-Tau (Ser199) and p-Tau (Thr231) were increased.

Conclusion:SBF can inhibit the hyperphosphorylated Tau protein expression levels at Ser199, Ser214, Ser404, and Thr231 sites by regulating PKA activity.