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

Abstract:

:Calprotectin is a calcium- and zinc-binding protein complex that is abundant in cytosol of neutrophils. The concentration of calprotectin in extracellular fluids is greatly increased under various inflammatory conditions in vivo. We recently demonstrated that calprotectin inhibited cell growth and induced apoptosis of various cell types including tumor cells and normal fibroblasts; therefore, extracellular calprotectin might cause tissue destruction 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, namely, lycoricidinol, hippeastrine and ungerine against the cytotoxicity of calprotectin. Lycoricidinol (narciclasine) inhibited calprotectin-induced cytotoxicity at more than 10-fold lower concentration (IC50=0.001-0.01 microg/ml) than lycorine, while the effects of the latter two alkaloids were very weak. Therefore, we next checked the prophylactic effect of lycorine and lycoricidinol on the adjuvant arthritis model in rats. Lycoricidinol, but not lycorine, significantly suppressed the degree of swelling of adjuvant-treated as well as untreated feet, suggesting that lycoricidinol might be a candidate as a the drug having marked suppressive activity for inflammation which might be influenced by calprotectin.

journal_name

Biol Pharm Bull

authors

Mikami M,Kitahara M,Kitano M,Ariki Y,Mimaki Y,Sashida Y,Yamazaki M,Yui S

doi

10.1248/bpb.22.674

subject

Has Abstract

pub_date

1999-07-01 00:00:00

pages

674-8

issue

7

eissn

0918-6158

issn

1347-5215

journal_volume

22

pub_type

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