The improvement and mechanism of Scutellaria baicalensis Georgi stems and leaves flavonoids on okadaic acid-induced learning and memory impairment in rats

Abstract

Abstract 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. 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. Methods The mimic AD model of memory impairment of rats was established by intracerebroventricular injection of OA. Morris water maze was to screen the successful model of memory impairment. The successful model rats were randomly divided into model group, three doses of groups for SSFs 25, 50, and 100 mg/kg, and positive drug Ginkgo biloba tablet (GLT) 200 mg/kg group. The rats’ learning and memory abilities were detected with the Morris water maze. The morphological changes of nerve cells were observed by hematoxylin-eosin (HE) staining. The Choline acetyltransferase (ChAT) protein expressions were detected with immunohistochemistry (IHC). The phosphorylation level of tau protein at Ser262 and Ser396 sites was assayed with Western blotting (WB). The activities of inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) were measured with ultraviolet spectrophotometry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Results The intracerebroventricular injection of OA caused the rats’ learning and memory impairment and neuropathological changes. The protein expression of ChAT was reduced (P < 0.01) and the phosphorylation levels of tau protein at Ser262 and Ser396 were significantly increased (P < 0.01), the activity of iNOS increased (P < 0.01) and cNOS decreased (P < 0.05) in the hippocampus and cerebral cortex. The levels of IL-1β and TNF-α in the cerebral cortex were increased (P < 0.01), and the level of IL-6 was decreased (P < 0.05). The three doses of SSFs and GLT treatment to rats can differently ameliorate the above abnormal changes caused by OA. Conclusion SSFs can improve the rats’ learning and memory impairment caused by intracerebroventricular injection of OA and the effective mechanism may be related to the positive regulation in ChAT protein expression, tau hyperphosphorylation, NOS activity, and inflammatory cytokine levels.