Physalin B Reduces Tau Phosphorylation and Cell Apoptosis in HEK293 Cells by Activating FoxO1

Background: Physalin B (PB) is one of the main active compounds of Solanaceae plants, with a wide range of biological activities. PB reportedly has the potential to treat Alzheimer’s disease (AD). Objective: In this study, we investigated the effect of PB on Tau phosphorylation and cell apoptosis using Tau-expressing HEK293 cells (HEK293/Tau) as a cellular model. Methods: The optimum concentration of PB to treat HEK293/Tau cells was determined using the CCK-8 assay. Additionally, the expression of FoxO1, Tau-5, p-Tau (T231, S262, and S404), ERK, p-ERK, GSK-3β, and p-GSK-3β was detected using western blotting to determine the effect of PB on Tau phosphorylation. The apoptosis rate was detected using flow cytometry, and the expression of Bax and Bcl-2 was detected using western blotting and verified using real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, cells were transfected with FoxO1 siRNA to downregulate FoxO1 expression, and the expression of the above-mentioned proteins was detected to verify the effect of PB on Tau phosphorylation and cell apoptosis. Results: After 24 h of PB treatment, the phosphorylation levels of Tau at S404, S262, and T231 sites decreased significantly, and the activities of GSK-3β and ERK were inhibited. PB also reduced cell apoptosis by reducing the expression of Bax and increasing the expression of Bcl-2. In addition, PB decreased Tau phosphorylation and cell apoptosis by upregulating FoxO1. Conclusion: The natural compound PB exhibited a protective effect in the AD cell model by increasing FoxO1 expression and reducing Tau phosphorylation and cell apoptosis.