Gastrodin Alleviates Tau Hyperphosphorylation Associated with AKT/GSK-3β Signaling Changes in an Alzheimer's Disease Cell Model.

Alzheimer's disease (AD) is a common neurodegenerative disease for which there are currently limited effective drugs. As the principal bioactive component derived from Gastrodia elata, Gastrodin (GAS) has shown clear therapeutic potential for treating AD; however, the molecular mechanism of its action remains to be elucidated. In this study, we aim to investigate the mechanism of the effect of GAS on AD model cells. Network pharmacology is employed to analyze the targets and signaling pathways affected by GAS in AD. An AD cell model is constructed by inducing human neuroblastoma SH-SY5Y cells with Okadaic acid (OA). Cell viability was assessed using the CCK-8 assay, while the levels of SOD, MDA, and T-AOC were measured. Apoptosis rate was determined through Annexin V-FITC/PI double staining, and expression of apoptosis-related factors, as well as AKT, GSK-3β, p-Tau (Ser396), and p-Tau (Thr181), was analyzed using RT-qPCR and Western blotting techniques. Network pharmacology analysis suggests that GAS has the potential to regulate cellular apoptosis and associated signaling pathways, including PI3K/AKT. Our experiments demonstrate that GAS can inhibit MDA levels, increase T-AOC and SOD in the AD model cells, and reduce cell apoptosis. Western blotting results indicate that GAS mitigates OA's inhibitory effects on p-AKT (Ser473) and p-GSK-3β (Ser9) expression. Additionally, it attenuates the overexpression of p-Tau (Ser396) and p-Tau (Thr181), suppresses Bax expression, and enhances Bcl-2 expression. GAS demonstrates the ability to ameliorate oxidative stress injury induced by OA and mitigate apoptosis. GAS may suppress Tau hyperphosphorylation, which is associated with changes in the AKT/GSK-3β signaling pathway, thereby exerting potential neuroprotective effects.