Flavonoids from Scutellaria baicalensis Georgi Stems and Leaves Regulate the Brain Tau Hyperphosphorylation at M|ultiple Sites Induced by Composited Aβ in Rats.

BACKGROUND Neurofibrillary tangles (NFTs), formed by hyperphosphorylation of Tau protein in Alzheimer's disease (AD) are the main pathomechanisms of neuronal degeneration, which can be used as a sign of brain disorder. It is positively correlated with the degree of cognitive impairment in AD. OBJECTIVE The objective of this study is to investigate the effect of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSF) on the hyperphosphorylated expression levels at multiple sites of Tau protein induced by β-amyloid protein 25-35 (Aβ25-35) in combined with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats. METHODS The model of rats for AD was established by intracerebroventricular injection of Aβ25-35 and AlCl3 combined with RHTGF-β1. On day 45 after the operation, the Morris water maze was used to screen the rats' memory impairment model for AD. The successful model rats were randomly divided into the model group and three-dose of drug group. The drug group rats were daily and orally SSF administrated for 38 days. Western blotting was used to detect the protein expression of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) in the hippocampus and cerebral cortex of rats. RESULTS Compared with the sham group, the protein expression of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) was significantly increased in the hippocampus and cerebral cortex in the model group (P < 0.01). However, the three doses of 35, 70 and 140 mg/kg SSF regulated the expression of phosphorylated Tau protein at the above sites to varying degrees in the hippocampus and cerebral cortex (P < 0.01) induced by composited Aβ. CONCLUSION SSF can significantly reduce the protein expression levels of P-Tau (Thr181), P-Tau (Thr217), P-Tau (Thr231), P-Tau (Ser199), P-Tau (Ser235), P-Tau (Ser396) and P-Tau (Ser404) in rats' brain induced by the intracerebroventricular injection of composited Aβ. These results demonstrated that the neuro-protection and the impaired memory improvement of SSF were due to the inhibition for the hyperphosphorylation of Tau protein at multiple sites.