Georgi stems and leaves flavonoids promote neuroregeneration and ameliorate memory loss in rats through cAMP-PKA-CREB signaling pathway based on network pharmacology and bioinformatics analysis.

The aim of this study was to investigate the possible molecular mechanism of Georgi stems and leaves flavonoids (SSF) in Alzheimer's disease (AD). The active ingredients of SSF and their targets were identified via network pharmacology and bioinformatics analysis. To test the successful establishment of a rat model of AD by Aβ combined with RHTGF- and AlCl, the Morris water maze test was used. To intervene, three different doses of SSF were administered. The model group and the control group were included among the parallel groups. A shuttle box test, immunohistochemistry, an enzyme-linked immunosorbent assay, qPCR and Western blot were performed to verify the results. Based on the intersection of genes among AD disease targets, SSF component targets, and differentially expressed genes in the single cell dataset GSE138852 and bulk-seq dataset GSE5281, nine genes related to the action of SSF on AD were identified. SSF have an important anti-AD pathway in the cAMP signaling pathway. SSF can ameliorate the conditioned memory impairment, augment Brdu protein expression and cAMP content; and differentially regulate the mRNA and protein expressions of GPCR, Gαs, AC1, PKA, and VEGF. The cAMP-PKA-CREB pathway in the SSF may mediate the ability of the SSF to ameliorate the composite-induced memory loss and nerve regeneration in rats induced by composite Aβ.