Ginsenoside Rg3 promotes beta-amyloid peptide degradation by enhancing gene expression of neprilysin.
OBJECTIVE
It has been hypothesized that the accumulation of beta-amyloid peptide (Abeta) in the brain is a triggering event leading to the pathological cascade of Alzheimer's disease. The steady-state levels of Abeta 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 Abeta 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 Abeta40 and Abeta42 in SK-N-SH cells transfected with Swedish mutant beta-amyloid precursor protein (SweAPP).


RESULTS
The ELISA result showed that Rg3 significantly reduced the levels of Abeta40 and Abeta42, 19.65 +/- 6.05%, 23.61 +/- 6.74%, respectively (P < 0.01). The Western blot analysis showed that Rg3 reduced the levels of Abeta40 and Abeta42 through enhancing NEP gene expression, and real-time PCR assay showed that 50 microM 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.
Yang
Lingling
L
Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan 250012, Shandong, China.
Hao
Jianrong
J
Zhang
Jing
J
Xia
Wenjun
W
Dong
Xifeng
X
Hu
Xiaoyan
X
Kong
Feng
F
Cui
Xing
X
D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D008516:Medicine, Chinese Traditional; D015260:Neprilysin / Q000187:drug effects* / Q000235:genetics; D009447:Neuroblastoma / Q000378:metabolism; D005894:Panax / Q000737:chemistry; D010446:Peptide Fragments / Q000187:drug effects* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D014162:Transfection
D016229:Amyloid beta-Peptides; D036145:Ginsenosides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C097367:ginsenoside Rg3; D015260:Neprilysin