Emodin attenuates systemic and liver inflammation in hyperlipidemic mice administrated with lipopolysaccharides.
Emodin attenuates systemic and liver inflammation in hyperlipidemic mice administrated with lipopolysaccharides.
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DOI：
10.1177/1535370214530247
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Jia X;Iwanowycz S;Wang J;Saaoud F;Yu F;Wang Y;Hu J;Chatterjee S;Wang Q;Fan D
非酒精性脂肪性肝病（NAFLD）是现代社会的一种主要流行病，其发病机制中有炎症成分。然而，目前还没有批准的抗炎疗法可用于预防从单纯性脂肪变性向非酒精性脂肪性肝炎（NASH）的转变。我们的目的是测试一种中药衍生化合物大黄素是否可以阻止简单脂肪变性向NASH的转变。LDLR−/−小鼠喂食西式饮食10周;在最后四周，小鼠每天腹腔注射LPS（含或不含大黄素）。通过测量血清细胞因子和趋化因子水平以及流式细胞术分析脾白细胞来评估全身炎症。通过组织学、免疫细胞化学和流式细胞术检测肝脏炎症。实时荧光定量PCR和Western blot检测大黄素对LPS诱导的巨噬细胞炎症反应的影响。我们的数据表明，大黄素改善全身炎症，减少肝脏中的炎性细胞浸润，减轻肝功能损害。体外实验表明大黄素通过抑制Erk 1/2和p38信号通路抑制LPS诱导的巨噬细胞促炎细胞因子的表达。总之，大黄素通过抑制全身炎症和巨噬细胞炎症抑制LPS攻击的高脂血症小鼠从单纯脂肪变性向NASH的转变。大黄素可能因其抗炎作用而被开发为NAFLD的治疗方法。
Non-alcoholic fatty liver disease (NAFLD) is a major epidemics of the modern societies and has an inflammatory component in the pathogenesis. However, approved anti-inflammatory therapies are not currently available for the prevention of the transition from simple steatosis to non-alcoholic steatohepatitis (NASH). We aimed to test if a Chinese herb-derived compound, emodin could halt the simple steatosis to NASH transition. LDLR−/− mice were fed a western-type diet for 10 weeks; and during the last four weeks, the mice were intra-peritoneally injected daily with LPS with or without emodin. Systemic inflammation was evaluated by measurement of serum levels of cytokines and chemokines and flow cytometric analysis of spleen leukocytes. Liver inflammation was determined by histology, immunocytochemistry and flow cytometry. Quantitative real-time PCR and Western blot were performed to examine the effects of emodin on LPS-induced inflammatory responses in macrophages. Our data showed that emodin ameliorated systemic inflammation, reduced inflammatory cell infiltration in the liver, and attenuated liver function impairment. In vitro experiments showed emodin inhibited LPS-induced expression of proinflammatory cytokines in macrophages through suppressing Erk1/2 and p38 signaling. In conclusion, emodin inhibited the transition from simple steatosis to NASH in hyperlipidemic mice challenged with LPS through suppressing systemic and macrophage inflammation. Emodin may be developed as a therapy for NAFLD by the virtue of its anti-inflammatory effects.