Cytotoxic saponins and other natural products from flowering tops of Narthecium ossifragum L.

For more than four centuries, the intake of Narthecium ossifragum has been associated with poisoning in domesticated animals. Saponins occurring in flowering tops of the plant are considered to cause kidney damage in calves. At present, there are more than 30 papers on the saponins of N. ossifragum in the literature, although the structures of these compounds have hitherto not been determined. Here, we identify the saponins of N. ossifragum as sarsasapogenin, sarsasapogenin-3- O - β -galactopyranoside, sarsasapogenin-3- O -(2′- O - β -glucopyranosyl- β -galactopyranoside) and sarsasapogenin-3- O -(2′- O - β -glucopyranosyl-3′- O - α -arabinopyranosyl- β -galactopyranoside). Moreover, six aromatic natural products were isolated and characterized from the methanolic extract from flowers of N. ossifragum. Five of these aromatic compounds, chrysoeriol 6- C - β -arabinofuranoside-8- C - β -glucopyranoside, chrysoeriol 6- C - β -arabinopyranosyl-8- C - β -glucopyranoside, chrysoeriol 6- C - β -xylopyranosyl-8- C - β -galactopyranoside, chrysoeriol 6- C - β -galactopyranosyl-8- C - β -glucopyranoside and chrysoeriol 6- C - β -glucopyranosyl-8- C - β -galactopyranoside are undescribed. All compounds were tested for cytotoxicity in mammalian cell lines derived from the heart, kidney, and haematological tissues. The saponins exhibited cytotoxicity in the micromolar range, with proportionally increasing cytotoxicity with increasing number of glycosyl substituents. The most potent compound was the main saponin sarsasapogenin-3- O -(2′- O - β -glucopyranosyl-3′- O - α -arabinopyranosyl- β -galactopyranoside), which produced cell death at concentrations below 3–4 μM in all three cell lines tested. This indicates that the saponins are the toxicants mainly responsible for kidney damage observed in cattle after ingestion of N. ossifragum. Our findings also pave the way for analysis of individual compounds isolated during the biopsies of intoxicated animals. Cytotoxic saponins from flowering tops of Narthecium ossifragum L. Andrea Estefanía Carpinteyro Díaz, Lars Herfindal, Bendik Auran Rathe, Kristine Yttersian Sletta, Svein Haavik and Torgils FossenCytotoxic saponins toxic to kidney cells were characterized from the hepatotoxic plant Narthecium ossifragum. Image 1 • Cytotoxic saponins of Narthecium ossifragum were for the first time identified. • Increasing cytotoxicity with increasing number of glycosyl substituents. • The main saponin was most toxic to all cell lines including kidney cells. • Five undescribed di-C-glycosylflavones were characterized. • Structures were established by 2D NMR and HRMS. [ABSTRACT FROM AUTHOR]