Bio-assay guided isolation and identification of anti-Alzheimer active compounds from the root of Angelica sinensis

Activity-directed fractionation and purification processes were employed to identify the anti-Alzheimer active compounds from the root of Angelica sinensis. In this study, the ability of Angelica root to inhibit the aggregated amyloid beta-peptide (agg A beta(1-40)) induced damage of differentiated PC-12 cells (dPC-12), a well-known cell model for Alzheimer disease, was investigated. Air-dried roots of A sinensis were extracted with methanol and then separated into ethyl acetate, n-butanol and water layers. Among them, only the ethyl acetate layer showed strong activity and therefore, subjected to separation and purification using various chromatographic techniques. Four compounds showing potent activity were identified by comparing spectral data (UV, NMR, and ESI-MS) with literature values to be Z-ligustilide, 11-angeloylsenkyunolide F, coniferyl ferulate and ferulic acid. They were found to significantly inhibit A beta(1-40) toxicity on dPC-12 cells at lower concentrations (1-10 mu g/ml), but at high concentrations (>50 mu g/ml) they were toxic to the dPC-12 cells, except 11-angeloylsenkyunolide F. DPPH scavenging activity of the extracts and isolated compounds have also been carried out to find the possible mechanism of the activity. (C) 2008 Published by Elsevier Ltd.