人参皂苷Rg1通过NFκB调节β-分泌酶的活性减少β-淀粉样蛋白的生成

Ginsenoside Rg1 is a represent ative effective component of the extracts of Ginseng. Recent domestic studies have demonstrated that ginsenoside Rg1 consumption prevented memory loss and improved cognitive function in a variety of animal models. Therefore, this study was designed to investigate whether ginsenoside Rg1 can modify APP metabolism and Aβ generation by NF-κB. In the present study, N2a/APP695 cells, an mutated APP overexpressed neuronal cell line, was applied to model APP metabolism and Aβ generation in vitro. Firstly, BACE1 mRNA and protein levels were detected by RT-PCR and Western blot, respectively. The enzymatically cleavaged APP fragment such as β-CTF and α-CTF were determined simultaneously. Then, the expression levels and subcellular localization of NF-κB were observed by Western blot and confocal laser scanning microscope, respectively. The results are as follows: Treatment of ginsenoside Rg1 at dose of 2.5 μM increased the protein level of NF-κB p65 in N2a/APP695 cells, and consequently, resulted in translocation of NF-κB from cytoplasm to nuclear in a time-dependent manner. The BACE1 mRNA and protein levels are decreased. These results suggest that ginsenoside Rg1 may modify the APP metabolism by enhancing nuclear NF-κB binding into BACE1 promoter, and thereby inhibiting the transcription and translation of BACE1, which may ultimately attenuate Aβ generation by amyloidgenesis pathway. Therefore, ginsenoside Rg1 is potentially a highly effective therapeutic agent in treating AD.