Xu Ge, Feng Lili, Song Pingping, Xu Fang, Li Ang, Wang Yubin, Shen Yan, Wu Xuefeng, Luo Qiong, Wu Xingxin, Sun Yang, Wu Xudong, Xu Qiang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xian Lin Road, Nanjing 210093, China.
The Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing 210014, China.
Int Immunopharmacol. 2016 Sep;38:175-85. doi: 10.1016/j.intimp.2016.05.027. Epub 2016 Jun 7.
Macrophage polarization plays an important role in inflammation. Regulation of the polarization has been reported to be effective therapeutics for various kinds of inflammatory diseases. The aims of the present study were to investigate the anti-inflammatory property of isomeranzin isolating from Murraya exotica as well as potential molecular mechanisms. Results showed that isomeranzin specifically reduced the M1 macrophage-associated pro-inflammatory cytokines through down-regulation of NF-κB and ERK signals. Immunoprecipitation and RNA silencing indicated suppression of isomeranzin in NF-κB activation was relying on the decreasing of TRAF6 ubiquitination. In vivo studies showed isomeranzin evidently inhibited LPS-induced sepsis for rising survival rate, improving tissue damage and lessening inflammatory cytokines. In accordance with in vitro studies, isomeranzin significantly blocked expression of p-p65 and p-ERK in lung and liver tissues. Moreover, isomeranzin ameliorated DSS and TNBS-induced colitis due to its anti-inflammatory effects. Taken together, isomeranzin suppressed inflammatory diseases by controlling M1 macrophage polarization through the NF-κB and ERK pathway.
巨噬细胞极化在炎症中起重要作用。据报道，调节极化是治疗各种炎症性疾病的有效方法。本研究的目的是研究从九里香中分离出的异紫堇素的抗炎特性及其潜在的分子机制。结果表明，异紫堇素通过下调NF-κB和ERK信号，特异性地降低了与M1巨噬细胞相关的促炎细胞因子。免疫沉淀和RNA沉默表明，异紫堇素对NF-κB激活的抑制作用依赖于TRAF6泛素化的降低。体内研究表明，异紫堇素通过提高存活率、改善组织损伤和减少炎症细胞因子，明显抑制了LPS诱导的败血症。与体外研究一致，异紫堇素显著阻断了肺和肝组织中p-p65和p-ERK的表达。此外，异紫堇素因其抗炎作用改善了DSS和TNBS诱导的结肠炎。综上所述，异紫堇素通过NF-κB和ERK途径控制M1巨噬细胞极化，从而抑制炎症性疾病。
