Inhibition of inducible nitric oxide synthase expression by yuccaol C from Yucca schidigera roezl.
Yucca schidigera extract finds wide commercial application in foods, cosmetics and pharmaceuticals. In a previous paper we have found as the main constituents of yucca bark, yuccaol A, B and C, new and very unusual spiro-derivatives made up of a C15 unit and a stilbenic portion closely related to resveratrol. This study was performed to examine whether yuccaol A, B or C (0.01-100 microM) could affect cytosolic inducible nitric oxide synthase (iNOS) protein expression and nitric oxide (NO) generation in vitro in Escherichia coli lipopolysaccharide (LPS)-activated J774.A1 macrophage cell line. NO production, detected as NO2-, increased significantly in LPS treated J774.A1 cells from 0.05 +/- 0.03 microM to 16.64 +/- 0.58 microM (P < 0.001). Yuccaol C (0.01-100 microM), added to the culture medium 1 h before LPS-stimulation, significantly (P < 0.001) and in a concentration related manner reduced NO release (P < 0.001) and iNOS protein expression (P < 0.05). In contrast, no inhibitory effect either on iNOS protein expression or on NO release was observed when yuccaol C was added after LPS stimulation. In contrast yuccaol A inhibited significantly (P < 0.001) only NO release at the highest concentration tested (100 microM) while yuccaol B did not reduce either NO release or iNOS expression. Yuccaol C was demonstrated to reduce iNOS protein expression via the transcription factor NF-kappaB. These results indicated that the empirical use of Y. schidigera as anti-inflammatory remedy could be addressed not only to the resveratrol content but also to the presence of yuccaol C.
Marzocco
Stefania
S
Department of Pharmaceutical Sciences, University of Salerno, via Ponte Don Melillo-84084, Fisciano, Salerno, Italy.
Piacente
Sonia
S
Pizza
Cosimo
C
Oleszek
Wieslaw
W
Stochmal
Anna
A
Pinto
Aldo
A
Sorrentino
Raffaella
R
Autore
Giuseppina
G
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D024202:Electrophoretic Mobility Shift Assay; D004794:Enzyme Repression / Q000187:drug effects; D004926:Escherichia coli; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D000077185:Resveratrol; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D013267:Stilbenes / Q000378:metabolism; D027623:Yucca / Q000737:chemistry*
D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D010636:Phenols; D010936:Plant Extracts; D013141:Spiro Compounds; D013267:Stilbenes; C488887:yuccaol C; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000077185:Resveratrol