Inhibition effect of Amaryllidaceae alkaloids, lycorine and lycoricidinol on macrophage TNF-alpha production

Citation
S. Yui et al., Inhibition effect of Amaryllidaceae alkaloids, lycorine and lycoricidinol on macrophage TNF-alpha production, YAKUGAKU ZA, 121(2), 2001, pp. 167-171
Citations number
11
Language
GIAPPONESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
ISSN journal
0031-6903 → ACNP
Volume
121
Issue
2
Year of publication
2001
Pages
167 - 171
Database
ISI
SICI code
0031-6903(200102)121:2<167:IEOAAL>2.0.ZU;2-5
Abstract
We previously demonstrated that Amaryllidaceae alkaloids, lycorine and lyco ricidinol, inhibit induction of apoptosis by calprotectin derived from neut rophils, and that the latter alkaloid showed suppression in rat adjuvant-in duced arthritis model. These findings suggest that the alkaloids have a mod ulating activity against inflammatory reaction. To explore further the mech anism of the suppression for inflammation, we studied the effect of the alk aloids on macrophage tumor necrosis factor (TNF-alpha) production in vitro, since TNF-alpha is recognized as a pivotal cytokine to regulate inflammati on. As a result of this study, lycorine and lycoricidinol inhibited TNF-alp ha production of murine macrophages stimulated with lipopolysaccharide (ID5 0 were 0.2 mug/ml and 0.002 mug/ml, respectively). The inhibition was also observed in macrophages treated by Gram-positive bacteria, Enterocossus fae calis. Both lycorine and lycoricidinol reportedly have inhibitory activity for protein biosynthesis. Although the inhibition of TNF-alpha production b y lycoricidinol was mainly due to the inhibition of protein biosynthesis, l ycorine showed inhibition against TNF-alpha production at lower concentrati ons than the case that they inhibited S-35-Cysteine/S-35-Methionine incorpo ration into macrophages. These facts suggest that the inhibition of TNF-alp ha production is not due to the inhibitory activity against protein transla tion at least at lower concentrations. From these results, it was concluded that these alkaloids exert inhibitory effects not only on neutrophil apopt osis-inducing protein, calprotectin, but also on macrophage TNF-alpha produ ction.