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. background: AD is a progressive neurodegenerative disease that seriously threatens the physical and mental health for the elderly. The disease is pathologically associated with Aβ plaque deposition, tau hyperphosphorylation, cholinergic damage, oxidative stress and neuroinflammation. okadaic acid (OA), an inhibitor of protein phosphatases PP1 and PP2A, can reduce the dephosphorylation of phosphorylated tau protein and result in the hyperphosphorylation of tau protein, which in turn leads to NFT deposition and indirectly induces AD. Therefore, the brain injury in mimic AD model established by intracerebroventricular injection of OA conforms to the pathogenesis of AD 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-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were measured using ELISA. objective: To investigate the effect and mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids (SSFs) on learning and memory impairment induced by intracerebroventricular injection of OA in rats. 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-1β 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. result: The intracerebroventricular injection of OA caused the rats’ learning and memory impairment and neuropathological changes. The protein expression of ChAT was reduced (P &amp;amp;amp;amp;amp;lt; 0.01) and the phosphorylation levels of tau protein at Ser262 and Ser396 were significantly increased (P &amp;amp;amp;amp;amp;lt; 0.01), the activity of iNOS increased (P &amp;amp;amp;amp;amp;lt; 0.01) and cNOS decreased (P &amp;amp;amp;amp;amp;lt; 0.05) in the hippocampus and cerebral cortex. The levels of IL-1β and TNF-α in the cerebral cortex were increased (P &amp;amp;amp;amp;amp;lt; 0.01), and the level of IL-6 was decreased (P &amp;amp;amp;amp;amp;lt; 0.05). The three doses of SSFs and GLT treatment to rats can differently ameliorate the above abnormal changes caused by OA.