Suppressive activity of lycoricidinol (narciclasine) against cytotoxicity of neutrophil-derived calprotectin, and its suppressive effect on rat adjuvant arthritis model

Calprotectin is a calcium- and zinc-binding protein complex that is abundan t in cytosol of neutrophils. The concentration of calprotectin in extracell ular fluids is greatly increased under various inflammatory conditions in v ivo. We recently demonstrated that calprotectin inhibited cell growth and i nduced apoptosis of various fell types including tumor cells and normal fib roblasts;; therefore, extracellular calprotectin might cause tissue destruc tion in severe inflammatory diseases. We previously found that an alkaloid, lycorine inhibits induction of apoptosis by calprotectin, In this paper we examined the inhibitory activities of other Amaryllidaceae alkaloids, name ly, lycoricidinol, hippeastrine and ungerine against the cytotoxicity of ca lprotectin, Lycoricidinol (narciclasine) inhibited calprotectin-induced cyt otoxicity at more than 10-fold lower concentration (IC50 = 0.001-0.01 mu g/ ml) than lycorine, while the effects of the latter two alkaloids were very weak. Therefore, we next checked the prophylactic effect of lycorine and ly coricidinol on the adjuvant arthritis model in rats. Lycoricidinol, but not lycorine, significantly suppressed the degree of swelling of adjuvant-trea ted as well as untreated feet, suggesting that lycoricidinol might be a can didate as a the drug having marked suppressive activity for inflammation wh ich might be influenced by calprotectin.