Excessive accumulation of amyloid-beta (A beta) has been proposed as a pivotal event in Alzheimer's disease (AD) pathogenesis. Possible mechanisms underlying A beta-induced neurotoxicity include inflammation and apoptosis. Here, the protective effect of ginsenoside Rg1 (GRg1) on neuronal damage was examined in an in vitro inflammatory neurodegeneration model. Supernatant from A beta(1-40)-stimulated THP-1 monocytes was added to SK-N-SH neuroblastoma cell culture medium. Incubation of SK-N-SH cells with cell-free supernatant from A beta(1-40) (125 nM)-treated THP-1 monocytes for 24 h significantly increased lactate dehydrogenase (LDH) release, cell apoptosis, Bax and caspase-3 expression in SK-N-SH cells. However, pretreating THP-1 monocytes with GRg1 (50, 100 or 150 mu M) for 30 min markedly reduced IL-1 beta, IL-8 and TNF-alpha levels in A beta(1-40)-stimulated supernatant. LDH release, cell apoptosis, Box and caspase-3 expression in SK-N-SH cells were significantly decreased when cultured with cell-free supernatant from A beta(1-40)-stimulated THP-1 monocytes that were pretreated with GRg1. The results suggest that A beta(1-40)-induced neuronal injury and apoptosis may be mediated by inflammatory monocyte reactions, and GRg1 exerts a protective effect against A beta(1-40)-induced neuronal injury and apoptosis, likely through its anti-inflammatory mechanism. (C) 2012 Elsevier Inc. All rights reserved.