Title:Flavonoids from Stem and Leaf of Scutellaria Baicalensis Georgi Inhibit the Phosphorylation on Multi-sites of Tau Protein Induced by Okadaic Acid and the Regulative Mechanism of Protein Kinases in Rats
Volume: 24
Issue: 7
Author(s): Yang Gao, Xiao-Qing Wang, Shuai Ma, Yong-Cai Dong and Ya-Zhen Shang*
Affiliation:
- Institute of Traditional Chinese Medicine, Chengde Medical College / Hebei Province Key Research Office of Traditional Chinese Medicine Against Dementia / Hebei Province Key Laboratory of Traditional Chinese Medicine Research and Development, An Yuan Road, Chengde 067000,China
Keywords:
Flavonoids from stem and leaf of Scutellaria baicalensis Georgi, Okadaic acid, Tau protein, phosphorylation sites,
CDK5, PKA, pTyr216-GSK3β, pSer9-GSK3β.
Abstract:
Aim: The present study aims to investigate the effect of flavonoids from stem and leaf
of Scutellaria Baicalensis Georgi (SSF) on multi-sites phosphorylation of tau protein in the cerebral
cortex and hippocampus of rats induced by okadaic acid (OA) and the regulative mechanism
of the protein kinases.
Methods: The model of AD-like memory impairment and neuronal injuries was established in
male SD rats who were microinjected with OA (200 ng/kg) to establish a memory impairment model
and screened for successful model rats by Morris water maze on day 21 after surgery. The successful
model rats were continuously administered with intragastric infusion (ig) SSF 25, 50 and
100 mg/kg or Ginkgo biloba leaves flavonoids (GLF) 200 mg/kg for 36 d. The relative protein expressed
levels of phosphorylated tau protein at sites of Ser199, Ser202, Ser214, Ser404 and
Thr231, protein kinases (CDK5, PKA, pTyr216-GSK3β and pSer9-GSK3β) were detected by Western
blotting.
Results: The relative protein expressed levels of p-tau(Ser199), p-tau(Ser202), p-tau(Ser214), p--
tau(Ser404), p-tau(Thr231) and pTyr216-GSK3β were significantly increased in both cerebral cortex
and hippocampus regions of the model rats subjected to intracerebroventricular injection of OA
(P<0.01), while the protein expressed levels of CDK5, PKA and pSer9-GSK3β (P<0.01) were reduced.
SSF can dramatically reverse these increments in phosphorylated tau protein levels
(P<0.01) and differently regulate the protein expressed levels of CDK5, PKA and GSK3β (P<0.01)
in rats’ cerebral cortex and hippocampus induced by OA. GLF also exhibit a similar effect to SSF.
Conclusion: The results demonstrated that SSF could inhibit the hyperphosphorylation of tau in
rats’ cerebral cortex and hippocampus induced by microinjection of OA, which may be related to
the activities of protein kinase CDK5, PKA and GSK3β.
