Ca2+-Camk-CREB Mediates the Effect of Flavonoids from Scutellaria Baicalensis Stems and Leaves on the Decrease of Neuroregeneration-Induced by Composited Aβ in Rats

ObjectiveTo investigate the effects of Scutellaria baicalensis stem-leaf flavonoid (SSF) on the decrease of neuroregeneration of rats induced by Aβ25-35 in combination with AlCl3 and RHTGF-β1 (composited Aβ) and its regulatory mechanism. MethodsThe healthy adult male Sprague Dawley (SD) rats were microinjected composited Aβ into cerebral ventricle to establish the model of mimic Alzheimer's disease (AD)．After 45 days of operation, Morris water maze was used to screen the memory impairment model, and the successful model rats were randomly divided into model group and three-doses of drug groups.Rats in the drug group were treated SSF by intragastric administration (ig) for 30 days, and the model group and the sham group rats were treated with the equal volume saline.Immunohistochemistry was used to detect the expression of NeuN protein in the hippocampal gyrus of rats, and the expression levels of CaMKII, P-CREB-Ser133, FGF2, Egr-1 protein and mRNA expression levels of CaMKII, FGF2 and Egr-1 in the hippocampus and cerebral cortex of rats were detected by Western blotting and Quantitative real-time polymerase chain reaction (qPCR). ResultsImmunohistochemistry showed that the protein expression of NeuN in the hippocampal gyrus of the model group rats was significantly decreased, as compared with the sham group.Compared with the model group, three-doses of SSF can significantly increase the potein expression of NeuN in the hippocampal gyrus than that of model group.Compared with the sham group, the protein expressions levels of CaMKII, P-CREB-Ser133, FGF2 and Egr-1 by Western blotting detected were dramatically lowered, and the mRNA expression levels of CaMKII, FGF2 and Egr-1 by qPCR assayed showed differently alteration of hippocampus and cerebral cortex in model group.While SSF differently regulated the changes of CaMKII, P-CREB-Ser133, FGF2, Egr-1 proteins and CaMKII，FGF2, Egr-1 mRNA expressions in rats' hippocampus and cerebral cortex induced by composited Aβ. Conclusion: Intraventricular injection of composited Aβ can reduce the neuroregeneration， and CaMKII, P-CREB-Ser133, FGF2 and Egr-1 proteins and CaMKII, FGF2 and Egr-1 mRNA expression in the Ca 2+ -CaMK-CREB signaling pathway change. While SSF can reverse the decrease of neuroregeneration induced by composited Aβ, and the effective mechanism of SSF may be primarily from the regulation of SSF in CaMKII, p-CREB-Ser133, FGF2 and Egr-1 expressions in the Ca 2+ -CaMK-CREB signaling pathway.Keywords: flavonoid from Scutellaria stems and leaves；Alzheimer's disease; Neuroregeneration; Ca 2+ -CaMK-CREB Ca2+-Camk-CREB Mediates the Effect of Flavonoids from Scutellaria Baicalensis Stems and Leaves on the Decrease of Neuroregeneration-Induced by Composited Aβ in Rats International Journal of Medicinal Plants and Natural Products (IJMPNP)