Inhibition of NO Production by Grindelia argentina and Isolation of Three New Cytotoxic Saponins

• Published in: Chemistry & biodiversity 2014-02, Vol.11 (2), p.311-322
• Main Authors: Alza, Natalia P., Pferschy-Wenzig, Eva-Maria, Ortmann, Sabine, Kretschmer, Nadine, Kunert, Olaf, Rechberger, Gerald N., Bauer, Rudolf, Murray, Ana P.
• Format: Article
• Language: English
• Subjects: Asteraceae; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Cytotoxic activity; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Fibroblasts - drug effects; Fibroblasts - metabolism; Grindelia; Grindelia - chemistry; Grindelia argentina; Grindeliosides A - C; Hispidulin; Humans; Macrophages - drug effects; Macrophages - metabolism; Molecular Structure; Nitric oxide; Nitric Oxide - biosynthesis; Saponins; Saponins - chemistry; Saponins - isolation & purification; Saponins - pharmacology; Structure-Activity Relationship; Triterpene saponins
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.201300193

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‐β‐D‐xylopyranosyl‐(1→3)‐β‐D‐glucopyranosyl‐2β,3β,16α,23‐tetrahydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D‐xylopyranosyl‐(1→2)‐β‐D‐apiofuranosyl‐(1→3)‐β‐D‐xylopyranosyl‐(1→3)‐α‐L‐rhamnopyranosyl‐(1→2)‐α‐L‐arabinopyranosyl ester (2), 3‐O‐β‐D‐glucopyranosyl‐2β,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D‐xylopyranosyl‐(1→2)‐β‐D‐apiofuranosyl‐(1→3)‐β‐D‐xylopyranosyl‐(1→3)‐α‐L‐rhamnopyranosyl‐(1→2)‐α‐L‐arabinopyranosyl ester, (3) and 3‐O‐β‐D‐xylopyranosyl‐(1→3)‐β‐D‐glucopyranosyl‐2β,3β,23‐trihydroxyolean‐12‐en‐28‐oic acid 28‐O‐β‐D‐xylopyranosyl‐(1→2)‐β‐D‐apiofuranosyl‐(1→3)‐β‐D‐xylopyranosyl‐(1→3)‐α‐L‐rhamnopyranosyl‐(1→2)‐α‐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‐γ‐induced 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‐γ‐induced NO production (IC50 51.4 μM), while grindeliosides A–C were found to be cytotoxic, with grindelioside C being the most active against both CCRF‐CEM (IC50 4.2±0.1 μM) and MRC‐5 (IC50 4.5±0.1 μM) cell lines.