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 C-15 unit and a stilbenic portion closely related to resveratrol. This study was performed to examine whether yuccaol A, B or C (0.01 - 100 muM) 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 muM to 16.64 +/- 0.58 muM (P < 0.001). Yuccaol C (0.01-100 muM), 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 muM) 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. (C) 2004 Elsevier Inc. All rights reserved.