Abstract: Objective: To observe effect of baicalein on the expression of PI3K/Akt signaling pathway related factors in HT22 cells induced by Aβ25-35. Methods:The Aβ25-35 at 40 μmol·L-1 was used to intervened in HT22 cells for 24 hours to establish a dementia cell model. Four different concentrations(5,10,20,40 μmol·L-1) of baicalein were used to intervene in dementia cell models for 24 hours. The cell viability was detected by CCK-8 method, and the baicalein concentration with the highest cell viability was selected for subsequent trials. The trial models were divided into the control group,the Aβ25-35 group,and the baicalein group. Flow cytometry and Hoechest 33342 staining were used to detect cell apoptosis;JC-10 method was used to detect mitochondrial membrane potential;DCFH-DA method was used to detect levels of reactive oxygen species; Immunofluorescence was used to detect microtubule associated protein light chain 3 (LC3) protein expression;Western blot was used to detect the expression of selective autophagy adaptor protein(p62), autophagy key molecule yeast Atg6 homolog 1(Beclin-1), phosphatidylinositol 3- kinase(PI3K), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), serine/threonine protein kinase (Akt), phosphorylated serine/threonine protein kinase (p-Akt), and mammalian target of rapamycin (mTOR), and compared with the PI3K specific inhibitor LY294002. Results:Finally,a concentration of 10 μmol·L-1 of baicalein was chosen for the subsequent trial. Compared with those in the control group, the apoptosis rate, ROS level, p62 protein expression,and mTOR protein expression were increased in the Aβ25-35 group (P<0.05),while MMP level, LC3 expression,Beclin-1 protein expression,p-PI3K/PI3K ratio,and p-Akt/Akt ratio were decreased (P<0.05); Compared with those in the Aβ25-35 group, the cell apoptosis rate, ROS level, p62 protein expression, and mTOR protein expression in the baicalein group were decreased (P<0.05),while MMP levels,LC3 expression,Beclin-1 protein expression, p-PI3K/PI3K ratio, and p-Akt/Akt ratio were raised (P<0.05) . Compared with those in the baicalein group,the addition of PI3K inhibitor LY294002 resulted in a decrease in the ratio of p-PI3K/PI3K and p-Akt/ Akt,and an increase in mTOR protein expression (P<0.05) . Conclusion:Baicalein can significantly improve the mitochondrial function of HT22 cells induced by Aβ25-35, and reduce cell apoptosis and oxidative stress. Its antidementia effect is related to the activation of the PI3K/AKT signaling pathway and the increase of cellular autophagy levels.