The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Exp Parasitol. 2010 Dec;126(4):510-6. doi: 10.1016/j.exppara.2010.05.025. Epub 2010 May 31.
Here we report the effect of a partially purified alkaloid fraction (NUP) of Nuphar lutea on nuclear factor kappa B (NF-κB) expression and studied its mechanism of toxicity against Leishmania major in C3H mice peritoneal macrophages. NUP was found to be a mixture of thermo-stable dimeric sesquiterpene thioalkaloids containing mainly thionupharidines. The anti-leishmanial activity was shown to be mediated through the activation of NF-κB and increased iNOS production. Additionally, the nitric oxide inhibitor, N(G)-monomethyl-L-arginine (0.5mM) totally reverted the anti-leishmanial effect of NUP (0.25 and 0.5μg/ml). NUP was also shown to act as an anti-oxidant, almost completely inhibiting the macrophage respiratory burst activity. However, no elevated lysozyme (EC3.2.1.17) or β-galactosidase (EC3.2.1.23) activities were demonstrated in macrophages treated with NUP. This study suggests, that the activity of NUP is mediated by NF-κB activation and the production of nitric oxide which is dependent on the L-arginine:NO pathway.
在这里，我们报告了一种从黄色水罂粟（Nuphar lutea）中部分纯化的生物碱部分（NUP）对核因子 kappa B（NF-κB）表达的影响，并研究了其在 C3H 小鼠腹腔巨噬细胞中对利什曼原虫的毒性机制。NUP 被发现是一种含有主要硫鸟嘌呤的热稳定二聚倍半萜硫代生物碱混合物。抗利什曼活性是通过 NF-κB 的激活和 iNOS 产生的增加来介导的。此外，一氧化氮抑制剂 N(G)-单甲基-L-精氨酸（0.5mM）完全逆转了 NUP（0.25 和 0.5μg/ml）的抗利什曼活性。NUP 还被证明具有抗氧化作用，几乎完全抑制了巨噬细胞呼吸爆发活性。然而，用 NUP 处理的巨噬细胞中未表现出溶菌酶（EC3.2.1.17）或β-半乳糖苷酶（EC3.2.1.23）活性的升高。本研究表明，NUP 的活性是通过 NF-κB 的激活和一氧化氮的产生介导的，而一氧化氮的产生依赖于 L-精氨酸：NO 途径。
