Hepatoprotective and antioxidant activities of extracts from Salvia-Nelumbinis naturalis against nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet in mice.
Hepatoprotective and antioxidant activities of extracts from Salvia-Nelumbinis naturalis against nonalcoholic steatohepatitis induced by methionine- and choline-deficient diet in mice.
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DOI：
10.1186/s12967-014-0315-x
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发表时间：
2014-11-19
影响因子：
7.4
通讯作者：
Ji G
中科院分区：
文献类型：
--
作者：
Liu Y;Song H;Wang L;Xu H;Shu X;Zhang L;Li Y;Li D;Ji G
非酒精性脂肪性肝炎（NASH）是以肝脏脂肪变性和严重损伤为特征的非酒精性脂肪性肝病的晚期，目前仍缺乏有效的治疗方法。中药复方丹参（SNN）可有效改善非酒精性单纯性脂肪肝（NAFL）患者的症状。已有研究证实SNN可降低NAFL实验模型肝脏脂质沉积和血清转氨酶。本研究旨在确定SNN是否对小鼠NASH模型有效，并探讨其潜在的药理学机制。C57 BL/6 J小鼠喂食蛋氨酸和胆碱缺乏（MCD）饲料6周以诱导NASH。同时，SNN组和模型组分别每日灌胃SNN或生理盐水。给对照组小鼠提供标准饮食。检测血清生化指标和肿瘤坏死因子-α（TNF-α）。观察肝组织病理学变化，测定肝匀浆中甘油三酯和脂质过氧化物丙二醛（MDA）含量。通过定量RT-PCR或Western印迹分析确定与炎症、凋亡和氧化应激相关的基因的肝脏表达和/或活化。NASH模型中显示的显著肝脏脂肪变性被SNN预防。NASH小鼠肝损伤明显表现为血清转氨酶和胆红素水平升高，肝组织小叶炎症、促炎细胞因子升高和细胞凋亡上调。SNN给药可改善上述病理变化。模型大鼠肝脏MDA和细胞色素P450 2 E1水平的升高证实了氧化应激的失衡。核因子红细胞2相关因子2及其靶基因的肝脏表达下降，而模型小鼠中c-Jun N-末端激酶活化增加。用SNN治疗小鼠显著改善了氧化应激相关的有害因素。该研究表明，SNN可以保护肝脏免受MCD饮食诱导的严重脂肪变性和损伤，这表明SNN在NASH患者的治疗中具有潜在的用途。结果还表明，提高肝脏的抗氧化能力可能有助于潜在的肝保护机制。
Nonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease that is characterized by both steatosis and severe injury in liver, still lacks efficient treatment. The traditional Chinese formula Salvia–Nelumbinis naturalis (SNN) is effectively applied to improve the symptoms of nonalcoholic simple fatty liver (NAFL) patients. Previous studies have confirmed that SNN could reduce the liver lipid deposition and serum transaminases of NAFL experimental models. This study aims to determine whether SNN is effective for murine NASH model and investigate the underlying pharmacological mechanisms. C57BL/6 J mice were fed with methionine- and choline-deficient (MCD) diet for six weeks to induce NASH. Simultaneously, SNN or saline was intragastrically administered daily to the mice in the SNN or model group, respectively. A standard diet was given to the control mice. Serum biochemical indices and tumor necrosis factor-α were measured. Liver histopathology was observed, and the contents of triglycerides and lipid peroxide malondialdehyde (MDA) in liver homogenates were evaluated. The hepatic expression and/or activation of genes associated with inflammation, apoptosis, and oxidative stress were determined by quantitative RT-PCR or Western blot analysis. The prominent liver steatosis displayed in the NASH model was prevented by SNN. The liver injury of NASH mice was obviously manifested by the increased levels of serum transaminases and bilirubin, as well as the lobular inflammation, elevated pro-inflammatory cytokines, and upregulated apoptosis in liver tissues. SNN administration improved the aforementioned pathological changes. The increased hepatic levels of MDA and cytochrome P450 2E1 of the model confirmed the unregulated balance of oxidative stress. The hepatic expression of nuclear factor erythroid 2-related factor 2 and its target genes decreased, whereas c-Jun N-terminal kinase activation in the model mice increased. Treating the mice with SNN significantly improved oxidative stress-related harmful factors. This study shows that SNN can protect the liver from severe steatosis and damage induced by MCD diet, which suggests the potential use of SNN on the treatment of NASH patient. The results also indicate that improving the hepatic antioxidant capability of the liver may contribute to the underlying hepatoprotective mechanism.
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