Ginsenoside Rg1 attenuates tau phosphorylation in SK-N-SH induced by Aβ-stimulated THP-1 supernatant and the involvement of p38 pathway activation

Aim: In the present study we aimed to investigate the neuroprotective effect of ginsenoside Rg1 (GRg1) on neuronal damage examined in an adopted in vitro inflammatory neurodegeneration model and the involvement of p38 MAPK signal pathway. Main methods: The supernatant from A beta(1-40)-stimulated THP-1 monocytes was used as culture medium for SK-N-SH neuroblastoma cells which was used as target neuronal cells. The cell viability of SK-N-SH cells was assessed by detecting lactate dehydrogenase (LDH) leakage; the content of pro-inflammatory cytokine was measured by radioimmunoassay; the expressions of tau phosphorylation, p-38 and synaptophysin (SYN) were evaluated by western blot assay. The microtubule associated protein-2 (MAP-2) expression was confirmed by immunostaining. Key findings: Our results showed that incubation of the supernatant from A beta(1-40)-stimulated THP-1 cells with SK-N-SH neuroblastoma cells for 24 h significantly increased LDH leakage. tau and p-38 phosphorylation in SK-N-SH cells with increased interleukin (IL)-1 beta release into the supernatant of THP-1 cells. Pretreatment of THP-1 cells with GRg1 (50, 100 and 150 mu M) for 30 min before A beta(1-40)-stimulation inhibited THP-1 cell-mediated A beta neurotoxicity towards SK-N-SH neuroblastoma and also decreased IL-1 beta release into THP-1 supernatant dose-dependently. An inhibitor of p38 MAPK, SB203580, had the same effect. Significance: These results suggested that activation of the p38 cell signal pathway may be involved in monocyte-mediated A beta neurotoxicity towards SK-N-SH cells. Data obtained from this study demonstrated that GRg1 represented a potential treatment strategy for Alzheimer's disease (AD). (C) 2012 Elsevier Inc. All rights reserved.