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.

中文翻译：

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黄芩茎叶黄酮类化合物抑制冈田酸诱导的大鼠Tau蛋白多位点磷酸化及蛋白激酶的调控机制

【摘要】：目的:探讨黄芩(Scutellaria Baicalensis Georgi, SSF)茎叶总黄酮对冈田酸(OA)诱导大鼠大脑皮层和海马tau蛋白多位点磷酸化的影响及其调控机制。的蛋白激酶。

方法：雄性SD大鼠微量注射OA（200 ng/kg）建立AD样记忆障碍和神经元损伤模型，建立记忆障碍模型，并于注射后第21天通过Morris水迷宫筛选成功模型大鼠。手术。成功的模型大鼠连续灌胃（ig）SSF 25、50和100 mg/kg或银杏叶黄酮（GLF）200 mg/kg 36 d。通过蛋白质印迹法检测Ser199、Ser202、Ser214、Ser404和Thr231位点磷酸化tau蛋白的相对蛋白表达水平，蛋白激酶（CDK5、PKA、pTyr216-GSK3β和pSer9-GSK3β）。

结果：p-tau(Ser199)、p-tau(Ser202)、p-tau(Ser214)、p--tau(Ser404)、p-tau(Thr231)和pTyr216-GSK3β的相对蛋白表达水平显着升高OA脑室内注射模型大鼠大脑皮层和海马区的蛋白表达水平降低（P<0.01），而CDK5、PKA和pSer9-GSK3β蛋白表达水平降低（P<0.01）。SSF 可以显着逆转磷酸化 tau 蛋白水平的这些增加（P<0.01），并不同程度地调节 OA 诱导的大鼠大脑皮层和海马中 CDK5、PKA 和 GSK3β 的蛋白表达水平（P<0.01）。GLF 也表现出与 SSF 类似的效果。