Leishmania major: Anti-leishmanial activity of Nuphar lutea extract mediated by the activation of transcription factor NF-κB
Leishmania major: Anti-leishmanial activity of Nuphar lutea extract mediated by the activation of transcription factor NF-κB
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DOI：
10.1016/j.exppara.2010.05.025
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发表时间：
2010-12-01
影响因子：
2.1
通讯作者：
Gopas, Jacob
中科院分区：
文献类型：
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作者：
Ozer, Lital;El-On, Joseph;Gopas, Jacob
在这里，我们报道了黄花莲部分纯化的生物碱组分 (NUP) 对核因子 kappa B (NF-kappa B) 表达的影响，并研究了其对 C3H 小鼠腹腔巨噬细胞中的利什曼原虫的毒性机制。 NUP被发现是热稳定的二聚倍半萜硫代生物碱的混合物，主要含有硫代芘啶。抗利什曼原虫活性是通过激活 NF-κ B 和增加 iNOS 产生来介导的。此外，一氧化氮抑制剂 N-G-单甲基-L-精氨酸 (0.5 mM) 完全恢复了 NUP（0.25 和 0.5 ug/ml）的抗利什曼原虫作用。 NUP 还被证明具有抗氧化剂的作用，几乎完全抑制巨噬细胞的呼吸爆发活动。然而，在用 NUP 处理的巨噬细胞中没有发现溶菌酶 (EC3.2.1.17) 或 β-半乳糖苷酶 (EC3.2.1.23) 活性升高。这项研究表明，NUP 的活性是由 NF-kappa B 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。 (C) 2010 Elsevier Inc. 保留所有权利。
Here we report the effect of a partially purified alkaloid fraction (NUP) of Nuphar lutea on nuclear factor kappa B (NF-kappa B) 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-kappa B and increased iNOS production. Additionally, the nitric oxide inhibitor, N-G-monomethyl-L-arginine (0.5 mM) totally reverted the anti-leishmanial effect of NUP (0.25 and 0.5 ug/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 beta-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-kappa B activation and the production of nitric oxide which is dependent on the L-arginine:NO pathway. (C) 2010 Elsevier Inc. All rights reserved.