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Background The present study was aimed to investigate the effect and molecular mechanism of Scutellaria barbata flavonoids (SBFs) in promoting neurogenesis and improving memory impairment mediated by CREB phosphorylation in rats. Methods Alzheimer’s disease (AD) model was established by intracerebroventricular injection of amyloid beta-peptide 25–35 (Aβ25−35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats. The Morris water maze was used to screen the successful AD model of rats. The screened successful AD model rats were randomly divided into three groups including a model group and two drug groups of 140 mg/kg SBFs and 0.5 mg/kg Rolipram (Positive control drug). After administration for 38 days, the Morris water maze test was used to measure the learning and memory ability of the rats. HE staining was used to observe the morphology of neurons in the hippocampus and cerebral cortex regionsof the rats' brains. Immunohistochemistry was used to detect the expression of NeuN in the hippocampal gyrus of rats. The mRNA expression of TrkB, RSK,CREB, and BDNF and the protein expression of NeuN, TrkB, RSK, P-CREB-Ser133, and BDNF in the hippocampus and cerebral cortex of the rats were assayed by quantitative real-time PCR (qPCR) and Western blotting methods. Results Intracerebroventricular injection of composited Aβ induced memory impairment, impaired neurons, decreased the protein expression of NeuN in the hippocampal gyrus, increased the mRNA expression levels of TrkB, RSK and BDNF, decreased the mRNA expression level of CREB and the protein expression levels of NeuN, TrkB, RSK, P-CREB-Ser133 and BDNF in the hippocampus and cerebral cortex of rats. However, SBFs attenuated memory impairment which was induced by composited Aβ in rats and ameliorated neuropathological changes in the brain, increased the expression of NeuN protein in the hippocampal gyrus, and regulated mRNA and protein expressions in composited Aβ treated rats. Rolipram ameliorated learning and memory disorder induced by composited Aβ, increased the protein expression of P-CREB-Ser133, increased the expression of NeuN protein in the hippocampal gyrus, promoted neurogenesis, and improved the neuropathological changes in the brain. The effect of SBFs was also similar to Rolipram. Conclusion The effect of SBFs was consistent with the positive control drug Rolipram. SBFs could promote neurogenesis and improve learning and memory impairment in AD rats, and its mechanism was mediated by CREB phosphorylation. |
