Jia Xuemei, Iwanowycz Stephen, Wang Junfeng, Saaoud Fatma, Yu Fang, Wang Yuzhen, Hu Jun, Chatterjee Saurabh, Wang Qian, Fan Daping
Department of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia SC 29209, USA.
Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia SC 29209, USA.
Exp Biol Med (Maywood). 2014 Aug;239(8):1025-1035. doi: 10.1177/1535370214530247. Epub 2014 Apr 16.
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.
非酒精性脂肪性肝病（NAFLD）是现代社会的一种主要流行病，其发病机制中存在炎症成分。然而，目前尚无获批的抗炎疗法可用于预防单纯性脂肪变性向非酒精性脂肪性肝炎（NASH）的转变。我们旨在测试一种源自中药的化合物大黄素是否能阻止单纯性脂肪变性向NASH的转变。给低密度脂蛋白受体（LDLR）基因敲除小鼠喂食西式饮食10周；在最后四周，每天给小鼠腹腔注射脂多糖（LPS），同时或不同时注射大黄素。通过测量血清细胞因子和趋化因子水平以及对脾脏白细胞进行流式细胞术分析来评估全身炎症。通过组织学、免疫细胞化学和流式细胞术确定肝脏炎症。进行定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法（Western blot）以检测大黄素对LPS诱导的巨噬细胞炎症反应的影响。我们的数据表明，大黄素可改善全身炎症，减少肝脏中的炎症细胞浸润，并减轻肝功能损害。体外实验表明，大黄素通过抑制细胞外信号调节激酶1/2（Erk1/2）和p38信号传导，抑制LPS诱导的巨噬细胞中促炎细胞因子的表达。总之，大黄素通过抑制全身和巨噬细胞炎症，抑制了高脂血症小鼠在LPS刺激下从单纯性脂肪变性向NASH的转变。大黄素因其抗炎作用，有望开发成为治疗NAFLD的药物。
