Mangiferin ameliorates fatty liver via modulation of autophagy and inflammation in high-fat-diet induced mice
Mangiferin ameliorates fatty liver via modulation of autophagy and inflammation in high-fat-diet induced mice
复制标题
芒果苷通过调节高脂饮食诱导的小鼠的自噬和炎症来改善脂肪肝
DOI：
10.1016/j.biopha.2017.10.022
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发表时间：
2017-12-01
影响因子：
7.5
通讯作者：
Sun, Ying
中科院分区：
文献类型：
--
作者：
Wang, Hu;Zhu, Yang-Yang;Sun, Ying
非酒精性脂肪肝（NAFLD）是全球最常见的肝病。NAFLD的进展是复杂的，并且与炎症、氧化应激、自噬、内质网应激和胰岛素抵抗相关。芒果苷是一种天然的C-葡萄糖基氧杂蒽酮，具有多种生物活性。本研究旨在探讨芒果苷对NAFLD的治疗作用及其分子机制。我们使用高脂饮食（HFD）建立了小鼠NAFLD模型，并向小鼠注射不同剂量的芒果苷（15、30和60 mg/kg，腹腔注射）12周。评估肝组织以评价炎症反应、自噬和糖脂代谢的变化。我们发现芒果苷降低体重，以及血浆和肝脏中甘油三酯和总胆固醇的水平。它还增加了HFD喂养小鼠的葡萄糖耐量。此外，芒果苷通过抑制核因子κ B和c-Jun N-末端激酶的活性来降低炎症反应，通过AMP活化的蛋白激酶/雷帕霉素信号传导途径的机械靶点来调节自噬，并且通过调节胰岛素受体底物/磷酸肌醇3-激酶/蛋白激酶B信号传导途径来改善糖脂代谢。这项研究表明，芒果苷通过抑制炎症反应、激活自噬和改善糖脂代谢，显著改善HFD喂养小鼠的NAFLD发展。
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease globally. The progression of NAFLD is complex and associated with inflammation, oxidative stress, autophagy, endoplasmic reticulum stress, and insulin resistance. Mangiferin, a natural C-glucosyl xanthone, has been reported to show multiple biological activities. The aim of this study was to investigate the therapeutic effect of mangiferin on NAFLD and the underlying molecular mechanism. We established a mouse model of NAFLD using a high-fat diet (HFD), and injected the mice with different doses of mangiferin (15, 30, and 60 mg/kg, intraperitoneal) for 12 weeks. Liver tissue was assessed to evaluate changes in inflammatory responses, autophagy, and glycolipid metabolism. We found that mangiferin decreased body weight, as well as the levels of triglycerides and total cholesterol in plasma and the liver. It also increased glucose tolerance in HFD-fed mice. In addition, mangiferin decreased inflammatory responses by inhibiting the activities of nuclear factor kappa B and c-Jun N-terminal kinase, regulated autophagy via the AMP-activated protein kinase/mechanistic target of rapamycin signaling pathway, and improved glycolipid metabolism via modulation of the insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B signaling pathway. This study demonstrated that mangiferin significantly ameliorates NAFLD development in HFD-fed mice by inhibiting inflammatory responses, activating autophagy, and improving glycolipid metabolism.