Ginsenoside Rg1 inhibits beta-secretase activity in vitro and protects against Abeta-induced cytotoxicity in PC12 cells.
Ginsenoside Rg1 (1) is a major active component of Panax notoginseng, a Chinese herb widely used in traditional Chinese medicine to improve learning and memory function. Increasing evidence suggests that beta-amyloid peptide (Abeta) plays a central role in the pathophysiology of Alzheimer's disease (AD). To elucidate the mechanism of 1 on improving the ability of learning and memory, we investigated whether 1 could affect Abeta generation or protect Abeta-induced neurotoxicity. The results showed that 1 could inhibit beta-secretase activity in vitro and also protect the PC12 cells against injuries caused by exposure of PC12 cells to 50 microM Abeta(25-35) for 48 h. The cell death, LDH release, NO release, ROS production, lipid peroxidation, intracellular calcium elevation, and apoptosis are associated events induced by Abeta that can be rescued by 1 in PC12 cells. In conclusion, 1 may be a promising agent for AD, and the mechanism is related to beta-secretase inhibition and protection against Abeta-induced cytotoxicity.
Wang
Yue-Hua
YH
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Du
Guan-Hua
GH
D000544:Alzheimer Disease / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D036145:Ginsenosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D016716:PC12 Cells; D005894:Panax / Q000737:chemistry*; D051381:Rats
D016229:Amyloid beta-Peptides; D036145:Ginsenosides; D009569:Nitric Oxide; D053829:Amyloid Precursor Protein Secretases; D053148:Caspase 3; C035054:ginsenoside Rg1