IVSE, isolated from Inula japonica,suppresses LPS-induced NO production via NF-κB and MAPK inactivation in RAW264.7 cells
IVSE, isolated from Inula japonica,suppresses LPS-induced NO production via NF-κB and MAPK inactivation in RAW264.7 cells
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DOI：
10.1016/j.lfs.2015.01.008
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发表时间：
2015-03-01
期刊：
影响因子：
6.1
通讯作者：
Kong, Dexin
中科院分区：
文献类型：
--
作者：
Chen, Xi;Tang, Sheng-An;Kong, Dexin
目的：本实验室前期研究表明，旋覆花提取物具有较好的抗肿瘤活性。（一）日本）具有抗炎和抗哮喘活性。为了从I.日本，我们最近分离了1，6 α-二羟基-4 α H-1，10-断连丝-5（10），11（13）-二烯-12，8 β-双（SE），6 α-异丁酰氧基-1-羟基-4 α H-1，10-断连丝-5（10），11（13）-二烯-12，8 β-双（IBSE），和6 α-异戊酰氧基-1-羟基-4 α H-1，10-断连丝-5（10），11（13）-dien-12，8 beta-diferase（IVSE）从I.结果表明：（1）化合物对脂多糖（LPS）刺激的RAW264.7细胞产生一氧化氮（NO）有明显的抑制作用。用Griess试剂检测IVSE、SE和IBSE对LPS诱导的RAW264.7细胞产生NO的抑制作用，以及IVSE对诱导型一氧化氮合酶（iNOS）及其上游信号蛋白I κ B激酶（IKK）、抑制剂κ B（I κ B）-α/核因子κ B（NF-κ B）和促分裂原活化蛋白激酶（MAPK）通过Western印迹进行研究。IVSE显示出最有效的抑制NO的产生。机制分析表明，IVSE显著降低iNOS的表达，通过阻断I κ B-α的磷酸化和降解，减少NF-κ B B亚单位p65向核内的转位，抑制上游介导因子IKK α/β的激活。IVSE可抑制细胞外调节激酶（ERK 1/2）、c-Jun N末端激酶（JNK）和p38等MAPK的磷酸化。意义：IVSE通过抑制NO的产生发挥抗炎作用，其机制可能与NE-κ B和MAPK的失活有关。我们的研究结果表明，IVSE可能成为一种抗炎药物的候选者。(C)2015 Elsevier Inc. All rights reserved.
Aims: Our previous study showed that the extract of Inula japonica Thunb. (I. japonica) has anti-inflammatory and anti-asthmatic activities. In an attempt to find anti-inflammatory compounds from I. japonica, we recently isolated 1,6 alpha-dihydroxy-4 alpha H-1,10-secoeudesma-5(10),11(13)-dien-12,8 beta-olide (SE), 6 alpha-isobutyryloxy-1-hydroxy-4 alpha H-1,10-secoeudesma-5(10),11(13)-dien-12,8 beta-olide (IBSE), and 6 alpha-isovaleryloxy-1-hydroxy-4 alpha H-1,10-secoeudesma-5(10),11(13)-dien-12,8 beta-olide (IVSE) from the extract of I. japonica, and investigated their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.Main methods: The inhibitory effect of IVSE, SE and IBSE on NO production in LPS-induced RAW264.7 cells was examined using Griess reagent, and the effects of IVSE on the expressions of inducible nitric oxide synthase (iNOS) and its upstream signal proteins including I kappa B kinase (IKK)/inhibitor kappa B (I kappa B)-alpha/nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) were investigated by Western blot.Key findings: Among the 3 compounds isolated, SE, IBSE, and IVSE inhibited NO production at 2.5 mu M with 5.1%, 40.4%, and 52.8%, respectively. IVSE displayed the most potent inhibition of NO production. Mechanism analysis indicated that IVSE dramatically decreased the expression of iNOS, reduced the translocation of the NF-kappa B subunit p65 into the nucleus by interrupting the phosphorylation and degradation of I kappa B-alpha, and inhibited the activation of the upstream mediator IKK alpha/beta. Furthermore, our results showed that IVSE inhibited the phosphorylation of MAPKs including extracellular regulated kinases (ERK1/2), c-Jun N-terminal kinases (JNK) and p38.Significance: IVSE exhibited anti-inflammatory activity by inhibiting NO production, in which inactivation of NE-kappa B and MAPKs might be involved. Our results suggest that IVSE might become an anti-inflammatory drug candidate. (C) 2015 Elsevier Inc. All rights reserved.