title: Inhibition of NO production by Grindelia argentina and isolation of three new cytotoxic saponins.
abstract: 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.
authors.affiliation: INQUISUR-CONICET, Departamento de Química, Universidad Nacional del Sur, Avenida Alem 1253, Bahía Blanca, 8000, Argentina (phone: +54-291-4595101 ext 3538; fax: +54-291-4595187).
authors.forename: Natalia P
authors.initials: NP
authors.lastname: Alza
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Pferschy-Wenzig
authors.forename: Sabine
authors.initials: S
authors.lastname: Ortmann
authors.forename: Nadine
authors.initials: N
authors.lastname: Kretschmer
authors.forename: Olaf
authors.initials: O
authors.lastname: Kunert
authors.forename: Gerald N
authors.initials: GN
authors.lastname: Rechberger
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
authors.forename: Ana P
authors.initials: AP
authors.lastname: Murray
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D036623:Grindelia / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis*; D012503:Saponins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D012503:Saponins; D009569:Nitric Oxide
keywords: Cytotoxic activity; Grindelia argentina; Grindeliosides A - C; Hispidulin; Nitric oxide; Saponins; Triterpene saponins