OBJECTIVETo assess the neuroprotective effects of ginsenoside Rg1 against β-amyloid peptide (Aβ(25-35))-induced apoptosis in primarily cultured rat cortical neurons.

METHODSPrimarily cultured cortical neurons were obtained from embryonic (E18d) rat fetus and maintained in neurobasal medium for 7d. Primary neurons pretreated with 1 μmol/L, 10 μmol/L or 20 μmol/L Rg1 for 24 h were challenged with 10 μmol/L Aβ(25-35) for 72 h. Morphological changes of neurons were evaluated; mitochondrial membrane potential (ΔΨm) was measured; with JC-1 staining and the expression of neural apoptosis-related proteins was detected by Western blot analysis.

RESULTSExposure to Aβ(25-35) for 72 h caused serious neural cell insults. A pretreatment with Rg1 significantly reduced Aβ(25-35)induced cell death in a dose-dependent manner, with a maximal effect (-90%) obtained at 20 μmol/L. The JC-1 staining results demonstrated the loss of ΔΨm after Aβ(25-35) treatment, while Rg1 maintained the normal level of ΔΨm. A series of mitochondrion-mediated apoptotic events happened after Aβ(25-35) treatment, such as decrease of Bcl-2/Bax, release of cytochrome C and activation of caspase 9 and caspase 3, which were all blocked by Rg1 pretreatment. Both estrogen receptor (ER) antagonist ICI182, 780 and glucocorticoid receptor (GR) antagonist RU486 blocked the antiapoptotic effects of Rg1.

CONCLUSIONGinsenoside Rg1 protects primary cultured rat cortical neurons from Aβ(25-35)-induced injury, which may be associated with mitochondrion-mediated antiapoptosis pathway.