Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-κB Activation.
Torilin Inhibits Inflammation by Limiting TAK1-Mediated MAP Kinase and NF-κB Activation.
复制标题
DOI：
10.1155/2017/7250968
复制
发表时间：
2017
影响因子：
4.6
通讯作者：
Rhee MH
中科院分区：
文献类型：
--
作者：
Endale M;Kim TH;Kwak YS;Kim NM;Kim SH;Cho JY;Yun BS;Rhee MH
托里林是从香菇果实中分离得到的一种倍半萜类化合物，具有抗菌、抗癌、抗炎等活性。然而，关于托林抗炎作用机制的数据有限。本研究采用体外炎症模型，研究托林在脂多糖诱导的炎症反应中的抗炎作用。我们检测了托林对内毒素刺激的RAW 264.7巨噬细胞炎症介质和细胞因子表达水平的影响。评估核因子-kB和AP-1、MAP激酶和接头蛋白的参与情况。托林能显著抑制内毒素诱导的NO释放、诱导型一氧化氮合酶、前列腺素E_2、环氧合酶-2、核因子-α、IL-1β、IL-6和GM-CSFmRNA和蛋白的表达。另外，托林预处理能抑制MAPKs的表达。PD98059、SB203580和SP600125介导的iNOS和COX-2蛋白抑制进一步证实了ERK1/2、p38MAPK和JNK1/2的参与。此外，托林可减弱核因子-kB和AP-1的易位、DNA结合和报告基因转录。有趣的是，Torlin抑制了Tak1的激活，进而抑制了MAPK介导的jnk、p38、ERK1/2和AP-1(atf-2和c-jun)的激活以及IKK介导的I-κBα降解、p65/p50激活和易位。综上所述，结果揭示了抑制核因子-κB和AP-1调节的炎症介质和细胞因子的表达，表明测试化合物作为候选抗炎剂的潜力。
Torilin, a sesquiterpene isolated from the fruits of Torilis japonica, has shown antimicrobial, anticancer, and anti-inflammatory properties. However, data on the mechanism of torilin action against inflammation is limited. This study aimed at determining the anti-inflammatory property of torilin in LPS-induced inflammation using in vitro model of inflammation. We examined torilin's effect on expression levels of inflammatory mediators and cytokines in LPS-stimulated RAW 264.7 macrophages. The involvement of NF-kB and AP-1, MAP kinases, and adaptor proteins were assessed. Torilin strongly inhibited LPS-induced NO release, iNOS, PGE2, COX-2, NF-α, IL-1β, IL-6, and GM-CSF gene and protein expressions. In addition, MAPKs were also suppressed by torilin pretreatment. Involvement of ERK1/2, P38MAPK, and JNK1/2 was further confirmed by PD98059, SB203580, and SP600125 mediated suppression of iNOS and COX-2 proteins. Furthermore, torilin attenuated NF-kB and AP-1 translocation, DNA binding, and reporter gene transcription. Interestingly, torilin inhibited TAK1 kinase activation with the subsequent suppression of MAPK-mediated JNK, p38, ERK1/2, and AP-1 (ATF-2 and c-jun) activation and IKK-mediated I-κBα degradation, p65/p50 activation, and translocation. Together, the results revealed the suppression of NF-κB and AP-1 regulated inflammatory mediator and cytokine expressions, suggesting the test compound's potential as a candidate anti-inflammatory agent.