Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge
Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge
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Lycorine 通过抑制 P38 和 STAT 激活来抑制 RAW264.7 细胞中脂多糖诱导的 iNOS 和 COX-2 上调，并提高 LPS 攻击后小鼠的存活率
DOI：
10.1016/j.intimp.2011.11.018
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发表时间：
2012-01-01
影响因子：
5.6
通讯作者：
Yin, Zhimin
中科院分区：
文献类型：
--
作者：
Kang, Jingjing;Zhang, Yushun;Yin, Zhimin
石蒜碱是从石蒜科植物中提取的一种天然生物碱，对肿瘤细胞具有多种生物学效应。石蒜碱剂量依赖性地抑制LPS诱导的RAW264.7细胞中一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）蛋白水平的上调。此外，它还抑制LPS处理的RAW 264.7细胞释放NO、PGE（2）、TNF-α和IL-6。RT-PCR实验表明石蒜碱抑制LPS诱导的iNOS基因表达，但不抑制考克斯-2基因表达。此外，石蒜碱降低LPS诱导的小鼠死亡率。机制上，LPS诱导的P38和STATs通路的激活被石蒜碱显著抑制。石蒜碱不干扰ERK 1/2、JNK 1/2和NF-κ B通路的磷酸化。总之，石蒜碱抑制LPS诱导的促炎介质的产生，并增加LPS攻击后小鼠的存活率，表明石蒜碱可能在响应LPS中发挥抗炎作用。(C)2011 Elsevier B. V.保留所有权利。
As a natural alkaloid extracted from Amaryllidaceae, lycorine shows various biological effects on tumor cells. Here we show that lycorine dose-dependently inhibited the LPS-induced up-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein level in RAW264.7 cells. Besides, it also inhibited NO, PGE(2), TNF-alpha and IL-6 release from LPS-treated RAW264.7 cells. RT-PCR experiments showed that lycorine suppressed LPS-induced iNOS but not COX-2 gene expression. Moreover, lycorine decreased LPS-induced mortality in mice. Mechanistically, LPS-induced activation of P38 and STATs pathways was suppressed significantly by lycorine. In addition, lycorine did not interfere with the phosphorylation of ERK1/2, JNK1/2 and NF-kappa B pathways. In conclusion, lycorine inhibits LPS-induced production of pro-inflammatory mediators and increases the survival rate of mice after LPS challenge, suggesting that lycorine could play an anti-inflammatory role in response to LPS. (C) 2011 Elsevier B.V. All rights reserved.