A chronically elevated glucocorticoid level impairs memory and cognition. Manninotriose is the main oligosaccharide of Prepared Radix Rehmanniae, and Astragaloside IV (AS-IV) is the primary ingredient of Astragali Radix; they have been reported to possess neuroprotective effects. The aim of the present study was to investigate the protective effects of Manninotriose and AS-IV on corticosterone (CORT) induced neurotoxicity and the underlying mechanisms. Primary cultured hippocampal neurons from newborn Sprague Dawley rats were treated with CORT in the absence or presence of Manninotriose and AS-IV. Cell Counting Kit-8 experiments and fluorescein diacetate (FDA)/propidium iodide (PI) double staining were conducted to assess the activity and survival rate of neurons. Quantitative Real-time PCR (qRT-PCR) and western blot analysis were performed to detect the expression of glucocorticoid receptor (GR), zinc finger protein (Zif268) and synapsin 1 (SYN1). DNA methylation of the gene promoter was assessed by bisulfite sequencing (BSP) analysis. The results demonstrated that pre-treatment with Manninotriose and AS-IV significantly improved cell viability and survival rate, and ameliorated the downregulation of GR, Zif268 and SYN1 genes in CORT injured neurons. BSP analysis revealed that CORT was able to improve the CpG island methylation rate of SYN1. AS-IV was observed to decrease the hypermethylation of the SYN1 gene induced by CORT. The results of the present study indicated that Manninotriose and AS-IV may have a protective effect against CORT-induced damage and the downregulation of learning and memory associated genes in hippocampal neurons. Regulation of DNA methylation may be important in the pharmaceutical activities of AS-IV. Thus, Manninotriose and AS-IV may be effective agents against learning and memory impairment.
Keywords: Astragaloside IV; DNA methylation; Manninotriose; corticosterone; learning and memory relevant genes.