Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin

Abstract Objectives It has been hypothesized that the accumulation of beta-amyloid peptide (Aβ) in the brain is a triggering event leading to the pathological cascade of Alzheimer's disease. The steady-state levels of Aβ are determined by the metabolic balance between anabolic and catabolic activity and the dysregulation of this activity leads to Alzheimer's disease. Recent evidence has shown that neprilysin (NEP) is the rate-limiting enzyme in the Aβ degradation in the brain. Ginseng, the root of Panax ginseng C.A. Meyer, is widely used as a tonic for the prevention and treatment of age-related disorders in China. We aimed to investigate the basis of this use. Methods In this study, we investigated the effect of ginsenoside Rg3, one of the major active components of ginseng, on the metabolism of Aβ40 and Aβ42 in SK-N-SH cells transfected with Swedish mutant β-amyloid precursor protein (SweAPP). Results The ELISA result showed that Rg3 significantly reduced the levels of Aβ40 and Aβ42, 19.65 ± 6.05%, 23.61 ± 6.74%, respectively (P < 0.01). The Western blot analysis showed that Rg3 reduced the levels of Aβ40 and Aβ42 through enhancing NEP gene expression, and real-time PCR assay showed that 50 μM Rg3 could significantly enhance NEP gene expression (2.9 fold at 48 h). Conclusions Our findings suggest that the Rg3 compound of ginseng may be useful for treating patients suffering with Alzheimer's disease.