Flavonoids from Scutellaria attenuate okadaic acid-induced neuronal damage in rats.

PRIMARY OBJECTIVE: To study the effect of flavonoids isolated from aerial parts of Scutellaria baicalensis Georgi (SSF) on cerebral damage induced by okadaic acid (OA) in rats. METHODS AND PROCEDURES: OA was microinjected into the right lateral ventricle of male rats at a dose of 200 ng kg(-1) twice with a 3-day interval between injections to establish a model of Alzheimer's-disease-like cerebral damage. Neuronal morphology was observed with thionin staining and the expressions of glial fibrillary acidic protein (GFAP) and ß-amyloid peptide 1-40 (Aß1-40) were monitored via immunohistochemistry. The level of malondialdehyde (MDA) and the activities of glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) were measured using spectrophotometry. MAIN OUTCOMES AND RESULTS: The results showed that OA-treated rats exhibited marked neuronal damage accompanied by increased levels of Aß1-40 peptide and MDA accumulation, decreased GFAP protein expression and reduced GSH-Px and LDH activity in the brain. SSF at three doses (25, 50 and 100 mg kg(-1)) dramatically reversed the OA-induced changes in the brains of rats. CONCLUSION: SSF-mediated amelioration of OA-induced neuronal damage in rats provides a rationale for assessing SSF as a means of to reducing tau hyperphosphorylation and Aß expression in the treatment of Alzheimer's disease.

Scutellaria Baicalensis Georgi Stem and Leaf Flavonoids Ameliorate the Learning and Memory Impairment in Rats Induced by Okadaic Acid.

AIM: The objective of this study is to explore the impact and underlying mechanism of Scutellaria baicalensis Georgi stem and leaf flavonoids (SSFs) on cognitive impairment caused by intracerebroventricular injection of okadaic acid (OA) in rats. METHODS: An experimental model of Alzheimer's disease (AD) was induced in rats by intracerebroventricular injection of OA, resulting in memory impairment. The Morris water maze test was employed to confirm the successful establishment of the memory impairment model. The rats that exhibited significant memory impairment were randomly divided into different groups, including a model group, three SSFs dose groups (25, 50, and 100 mg/kg), and a positive control group treated with Ginkgo biloba tablets (GLT) at a dose of 200 mg/kg. To evaluate the learning and memory abilities of the rats, the Morris water maze test was conducted. Hematoxylin-eosin (HE) staining was used to observe any morphological changes in neurons. Immunohistochemistry (IHC) was performed to measure the expression of choline acetyltransferase (ChAT) protein. Western blotting (WB) was utilized to assess the phosphorylation levels of tau protein at Ser262 and Ser396. The activities of inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) were quantified using ultraviolet spectrophotometry. The levels of inflammatory factors, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were measured using ELISA. RESULTS: In rats, the administration of OA via intracerebroventricular injection resulted in cognitive impairment, neuropathological changes, and alterations in protein expression and activity levels. Specifically, the protein expression of ChAT was significantly reduced (P<0.01), while the phosphorylation levels of tau protein at Ser262 and Ser396 were significantly increased (P<0.01). Moreover, iNOS activity in the hippocampus and cerebral cortex exhibited a significant increase (P<0.01), whereas cNOS activity showed a decrease (P<0.05). Furthermore, the levels of IL-1ß and TNF-α in the cerebral cortex were elevated (P<0.01), while the level of IL-6 was decreased (P<0.05). The administration of three doses of SSFs and GLT to rats exhibited varying degrees of improvement in the aforementioned pathological alterations induced by OA. CONCLUSION: SSFs demonstrated the ability to enhance cognitive function and mitigate memory deficits in rats following intracerebroventricular injection of OA. This beneficial effect may be attributed to the modulation of ChAT protein expression, tau hyperphosphorylation, NOS activity, and inflammatory cytokine levels by SSFs.

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.

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-GSK3ß and pSer9-GSK3ß) 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-GSK3ß 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-GSK3ß (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 GSK3ß (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 GSK3ß.