Aim:The objective of this study is to explore the impact and underlying mechanism of
S. 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-1β (IL-1β), 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-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.