Inhibition of NO production in Grindelia argentina and isolation of three new cytotoxic saponins

ALZA, N.P.; PFERSCHY-WENZIG, E.; ORTMANN, S.; KRETSCHMER, N.; KUNERT, O.; RECHBERGER, R.; BAUER, R.; MURRAY, A.P.

Chemistry and Biodiversity

WILEY-V C H VERLAG GMBH

Lugar: Zurich; Año: 2014 vol. 11 p. 311 - 322

1612-1872

A bioassay-guided phytochemical analysis of the ethanolic extract of Grindelia argentina Deble & Oliveira-Deble (Asteraceae) allowed the isolation of a known flavone, hispidulin, and three new oleanane-type saponins, 3-O-b-d-xylopyranosyl-(1 3)-b-d-glucopyranosyl-2b,3b,16a,23 tetrahydroxyolean-12-en-28-oic acid 28-O-b-d-xylopyranosyl-(1 2)-b-d-apiofuranosyl-(1 3)-b-d-xylopyranosyl-(1 3)-a-l-rhamnopyranosyl-(1 2)-a-l-arabinopyranosyl ester (2), 3-O-b-d-glucopyranosyl-2b,3b,23-trihydroxyolean-12-en-28-oic acid 28-O-b-d-xylopyranosyl-(1 2)-b-d apiofuranosyl-(1 3)-b-d-xylopyranosyl-(1 3)-a-l-rhamnopyranosyl-(1 2)-a-l-arabinopyranosyl ester, (3) and 3-O-b-dxylopyranosyl-(1 3)-b-d-glucopyranosyl-2b,3b,23-trihydroxyolean-12-en-28-oic acid 28-O-b-d-xylopyranosyl-(1 2)-b-d-apiofuranosyl-(1 3)-b-d-xylopyranosyl-(1 3)-a-l-rhamnopyranosyl-(1 2)-a-l-arabinopyranosyl ester (4), named grindeliosides A?C, respectively. Their structures were determined by extensive 1D- and 2D-NMR experiments along with mass spectrometry and chemical evidence. The isolated compounds were evaluated for their inhibitory activities against LPS/IFN-ginduced NO production in RAW 264.7 macrophages and for their cytotoxic activities against the human leukemic cell line CCRF-CEM and MRC-5 lung fibroblasts. Hispidulin markedly reduced LPS/IFN-ginduced NO production (IC50 51.4 microM), while grindeliosides A?C were found to be cytotoxic, with grindelioside C being the most active against both CCRF-CEM (IC50 4.20 microM) and MRC-5 (IC50 4.50 microM) cell lines.