Isolation and structural elucidation of sesquiterpene lactones from Achillea millefolium L. and pharmacological investigation in an ICAM-1 in vitro model

Achillea millefolium is one of the most widely used medicinal plants in the world and has been used in folk medicine for millennia [1]. Its broad spectrum of pharmacological activity is mainly due to secondary metabolites such as flavonoids and sesquiterpenes, in particular sesquiterpene lactones (SL) [2]. Due to the promising potential of SLs for medical applications, in course of this work SLs were isolated from A. millefolium and their in vitro pharmacological potential was investigated. The structural elucidation was performed by means of one- and two-dimensional NMR spectroscopy and HRESIMS. The isolated compounds were four SLs of the germacranolide-type and eleven SLs of the guaianolide-type as well as three unsaturated fatty acids and one flavonol. Two isolated compounds have not yet been identified for the species A. millefolium and six SLs are described for the first time ([Fig. 1]). Furthermore, the biological activity of ten of these compounds was investigated using a human endothelial cell line (HMEC-1) as an ICAM-1 inflammation model [3]. For eight of the ten investigated compounds, a significant reduction in ICAM-1 production was detected which has not yet been described for any of these compounds. None of the investigated substances exhibited an exocyclic methylene structure. The reduced transcription of proinflammatory genes in literature is attributed in particular to this structure due to its interaction with the transcription factor NF-κB [4], [5]. However, these results verify the ability of other structural motifs to initiate an anti-inflammatory effect in vitro.