Anti-inflammatory effect of kamebakaurin in in vivo animal models
Anti-inflammatory effect of kamebakaurin in in vivo animal models
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DOI：
10.1055/s-2004-827152
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发表时间：
2004-06-01
期刊：
影响因子：
2.7
通讯作者：
Lee, JJ
中科院分区：
文献类型：
--
作者：
Lee, JH;Choi, JK;Lee, JJ
我们已经确定kamebakaurin作为NF-κ B的抑制剂，并阐明其作为NF-κ B的p50亚基的DNA结合活性的特异性抑制剂的分子机制。在这里，我们描述了其在体外和体内模型中的抗炎活性。在LPS刺激的RAW 264. 7细胞中，Kamebakaurin不仅剂量依赖性地抑制炎性NF-κ B靶基因如iNOS、考克斯-2和TNF-α的表达，而且抑制PGE（2）和TNF-α的产生。此外，在炎症的气囊模型中，它抑制中性粒细胞的募集、角叉菜胶诱导的气囊渗出物中TNF-α和PGE 2的产生。此外，kamebakaurin剂量依赖性地抑制佐剂性关节炎模型中的炎症。经口给予20 mg/kg kamebakaurin导致爪体积减少75%。综上所述，p50亚基的DNA结合活性的特异性抑制剂kamebakaurin是用于干预NF-κ B依赖性病理状况如炎症的有价值的候选物。
We have identified kamebakaurin as an inhibitor of NF-kappaB and elucidated its molecular mechanism as a specific inhibitor in the DNA-binding activity of the p50 subunit of NF-kappaB. Here, we describe its anti-inflammatory activity in in vitro and in vivo models. Kamebakaurin dose-dependently inhibited not only the expression of inflammatory NF-kappaB target genes such as iNOS, COX-2, and TNF-alpha, but also the production of PGE(2) and TNF-alpha in LPS-stimulated RAW264.7 cells. Moreover, in an air pouch model of inflammation, it suppressed the recruitment of neutrophils, production of TNF-alpha as well as PGE2 in the pouch exudates induced by carrageenan. In addition, kamebakaurin dose-dependently suppressed the inflammation in an adjuvant arthritis model. Oral administration of 20 mg/kg kamebakaurin resulted in the 75% decrease of paw volume. Taken together, kamebakaurin, a specific inhibitor of DNA-binding activity of the p50 subunit, is a valuable candidate for the intervention in NF-kappaB-dependent pathological conditions such as inflammation.