Scutellaria barbata Flavonoids Promote Nerve Regeneration and Ameliorate the Rats' Impaired Spatial Memory via the Ras-ERK-CREB Signaling Pathway

Aim: This study aims to investigate whether Scutellaria barbata flavonoids (SBFs) enhance nerve regeneration and ameliorate spatial memory impairment in an Alzheimer';s disease (AD) rat model, as well as the effective mechanism mediated by Ras-ERK-CREB signaling pathway. Methods: An AD model of rats was established by intracerebroventricular injection of Aβ25-35 combined with AlCl3 and RHTGF-β1 (composited Aβ). The successful model rats were screened with the Morris water maze and randomly divided into the model group, 140 mg/kg SBFs group, and 0.5 mg/kg Rolipram group. The spatial memory ability of the rats was tested with the Barnes maze. Nissl bodies in the nerve cells were observed with crystal violet staining. The expression of NeuroD1 was detected by immunohistochemistry. The mRNA and proteins of molecules in Ras-ERK-CREB signaling pathway were measured using real-time quantitative PCR and western blotting methods, respectively. CREB activator Rolipram was used as a positive control. Results: Intracerebroventricular injection of composited Aβ resulted in the rats' spatial memory impairment, both the density of intracellular Nissl bodies and the protein expression of NeuroD1 decreased, as well as the mRNA and protein expression of molecules disorder in Ras-ERKCREB signaling pathway in the brain. However, SBFs can enhance the spatial memory, increase Nissl body density, and NeuroD1 protein expression, and regulate the abnormal mRNA and protein expression levels of molecules in Ras-ERK-CREB signaling pathway induced by composited Aβ. Rolipram showed similar effects to SBFs. Conclusion: SBFs promote nerve regeneration and enhance spatial memory by regulating the Ras-ERK-CREB signaling pathway.