The ability of Epilobium extracts and polyphenols to induce neutral endopeptidase (NEP) activity and to inhibit the proliferation in cell lines with high NEP expression (SK-N-SH) and with low NEP expression (PC-3) was investigated. Epilobium extracts enhanced in a dose-depend manner NEP activity in both cell lines with additional inhibition of cell proliferation. The sensitivity of cells depended on basal enzyme activity. SK-N-SK cells were much more sensitive than PC-3 cells. Oenothein B enhanced NEP activity at a concentration of 5-40 microM while quercetin-3-glucuronide and quercetin-3-O-(6"-gal-loyl) galactoside showed slight or no activity at a concentration of 100 microM. The comparison of activities of the extracts with oenothein B, a dimeric macrocyclic ellagitannin, suggests that the latter is mostly responsible for the observed effects. Taking into account the role of NEP in the homeostasis of signalling peptides, Epilobium angustifolium extracts may be a potential herbal remedy in diseases connected with the disturbed metabolism of signaling peptides caused by an unbalanced neutral endopeptidase activity.