Effects of Panax notoginseng saponin on α, β, and γ secretase involved in Aβ deposition in SAMP8 mice

Our previous studies have shown that Panax notoginseng saponins (PNS) play a protective role in learning dysfunction of Alzheimer's disease, inhibit the deposition of Aβ1-40 and Aβ1-42, and reduce the content of App in the brain of SAMP8. In this study, we aimed to investigate the effects of PNS on α, β, and γ secretase involved in Aβ generation in SAMP8 mice. The results showed that PNS increased α-secretase activity perhaps by enhancing the level of ADAM9 expression, which itself was achieved by upregulating the expression of the ADAM9 gene. In addition, PNS significantly decreased BACE1 protein level by downregulating the level of BACE1 gene expression and consequently precluded the activity of β secretase. However, PNS treatment did not modify γ-secretase activity. Together, our study shows that PNS modulates the levels of protein and gene expressions involved with α and β secretase, thereby increasing α-secretase activity and reducing β-secretase activity, which may be one of the mechanisms of PNS precluding Aβ generation. Accordingly, PNS may be a promising agent for Alzheimer's disease.