Flavonoids from Stems and Leaves of Scutellaria baicalensis Georgi Regulate the Brain Tau Hyperphosphorylation at Multiple Sites Induced by Composited Aβ in Rats

Abstract

Background: Neurofibrillary Tangles (NFTs), formed by hyperphosphorylation of Tau protein in Alzheimer's Disease (AD), arethe main pathomechanisms of neuronal degeneration, which indicate a sign of brain disorder. NFTs are positively correlated with the degree of cognitive impairment in AD. Objective: The objective of this study isto investigate the effect of flavonoids from the stems and leaves of Scutellaria baicalensis Georgi (SSF) on the hyperphosphorylated expression levels at multiple sites of Tau protein induced by β-amyloid protein 25-35 (Aβ25-35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1(RHTGF-β1) (composited Aβ) in rats. Methods: The AD rat models were established by intracerebroventricular injection of Aβ25-35 and AlCl3 combined with RHTGF-β1. On day 45, after the operation, the Morris water maze test was conducted to screen the memory impairment of AD models. The successful model rats were randomly divided into the model group and the three-dose drug group. The drug group rats were orally administered SSF daily for 38 days. Western blotting was performed to detect the protein expression of P-Tau (Thr 181), P-Tau (Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-- Tau (Ser 396), and P-Tau (Ser 404) in the hippocampus and cerebral cortex of rats. Results: Compared with the sham group, the expression of P-Tau (Thr 181), P-Tau (Thr 217), P-- Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser 404)was significantly increased in the hippocampus and cerebral cortex of the model group (P < 0.01). However, the three doses of SSF, i.e., 35, 70, and 140 mg/kg, regulated the expression of phosphorylated Tau proteinto varying degrees in the hippocampus and cerebral cortex of AD model rats (P < 0.01). Conclusion: SSF could significantly reduce the protein expression levels of P-Tau (Thr 181), PTau (Thr 217), P-Tau (Thr 231), P-Tau (Ser 199), P-Tau (Ser 235), P-Tau (Ser 396), and P-Tau (Ser 404), induced by the intracerebroventricular injection of composited Aβ, in rats’ brain. These results indicated that the neuro-protection and the improvement in the impaired memory of rats by SSF were due to the inhibition of hyperphosphorylation of Tau protein at multiple sites in rats' brain.