Honokiol Regulates Phosphorylation of Tau via Inhibition of GSK3β

Abnormal phosphorylation of tau plays an important role in neurodegeneration and subsequent dementia in Alzheimer's desease (AD). Much effort has been dedicated to treat AD, including inhibits GSK3β which is major kinase responsible for hyperphosphorylated tau. Honokiol, one of the major components isolated from Magnolia obovata , has been reported to have variety of pharmacological activities including anti‐inflammation and neuroprotection. In this study, the main objective was to determine whether Honokiol has inhibitory effects on phosphorylation of tau via modulation of GSK3β activities. Honokiol suppressed phosphorylation of tau in a dose‐dependent manner and inhibited GSK3β in 293T cells. Cholinergic neuroblastoma cell lines, LA‐N‐2 or SN56.B5.G4 were differentiated by CNTF and the cells were treated with oligomeric Aβ for an AD‐like pathogenic condition. The cells showed morphological changes such as long processes and branches, cell death and aggregation in the presence of CNTF or Aβ. Treatment with Honokiol not only recovered morphological changes but also decreased the phosphorylation of tau and the activity of GSK3β in vitro. Although further experiments about CDK5 which is known as the other cause for tau phosphorylation are required, our results implies that Honokiol regulates the phosphorylation of tau and the phosphorylation of GSK3β.