Involvement of CDK4, pRB, and E2F1 in ginsenoside Rg1 protecting rat cortical neurons from beta-amyloid-induced apoptosis

To explore the possible mechanism of beta-amyloid (Abeta)-induced apoptosis in rat cortical neurons and the protective effect of ginsenoside Rg1.AO-EB staining was used to quantify the apoptotic cells. DNA fragmentation was observed by gel electrophoresis. The levels of cyclin-dependent kinases-4 (CDK4) and phosphorylated pRB were detected by Western blot. RT-PCR was used to examine the expression of E2F1 mRNA.Treatment with Abeta1-40 at the concentration of 20, 40, 80 mg/L for 48 h induced rat cortical neuron apoptosis from 12.5 %+/-1.5 % (control) to 22.3 %+/-1.4 %, 38.8 %+/-1.3 %, 36.7 %+/-1.4 %, respectively. Pretreatment with Rg1 at the dose of 0.5, 1, 2, 4, 8, 16 micromol/L for 24 h, then treatment with Abeta1-40 40 mg/L for 24 h, the percentage of apoptotic neurons decreased from 38.8 %+/-1.3 % to 14.5 %+/-1.3 %, 13.3 %+/-1.0 %, 11.6 %+/-0.29 %, 11.8 %+/-1.0 %, 6.2 %+/-0.8 %, 5.8 %+/-0.8 %, respectively. After treatment with Abeta1-40 40 mg/L for 24 h, there were transient increases in CDK4 and phosphorylated pRB protein level, as well as the expression of E2F1 mRNA. However, the above levels decreased markedly after pretreatment with Rg1 8 micromol/L for 24 h.Ginsenoside Rg1 attenuated Abeta1-40-induced apoptosis in rat cortical neurons via inhibiting the activity of CDK4, decreasing the phosphorylation of pRB and downregulating the expression of E2F1 mRNA.