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.

Abstract-The pharmacological effects of a new anti-inflammatory compound, a (3,5-di-tert-butyl-4-hydroxybenzylidene)-r-butyrolactone (KIVI E-4), and its inhibitory effects on arachidonate prostaglandin synthetase and 5-lipoxygenase activities were examined. KME-4 showed anti-inflammatory activity.It was less active than indomethacin, but more active than naproxen and ibuprofen in carrageenin-induced paw edema in rats; and it was less active than indomethacin, equipotent as naproxen, but more active than ibuprofen in granuloma formation in rats. The ulcerogenic activity of KME-4 was weaker than indomethacin and naproxen, but stronger than ibuprofen in starved rats. The ratio of UD50 stomach to ED30 carrageenin edema or to ED25 granuloma for KME-4 showed higher values than those of the reference drugs.

Expression of TGF-α α α α during promotion of neoplastic development from GST-P-positive foci in rat chemical hepatocarcinogenesis was investigated. One-hundred male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg bodyweight) and subjected to two-thirds partial hepatectomy at week 3.

We previously indicated that coumaperine isolated from pepper can protect against the initiation of rat hepatocarcinogenesis. In the present study, potential modifying effects of coumaperine on post-initiation promotion stage were examined, using a medium term rat liver bioassay (Ito test). F344 rats were given a single intraperitoneal injection of diethylnitrosamine (200 mg/kg body wt.) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, coumaperine at doses of 0, 2, 10, 50 mg/kg body wt. was given to the rats for 6 weeks. All surviving animals were killed at week 8, and their livers were immunohistochemically examined for expression of glutathione S-transferase placental form (GST-P) and transforming growth factor-α (TGF-α). The numbers and areas of GST-P positive foci in rats given 2, 10 or 50 mg/kg coumaperine were comparable to the control values. There were also no significant intergroup differences regarding numbers and areas of TGF-α positive foci. This study suggested that coumaperine does not inhibit liver carcinogenesis in the promotion stage.