Limonin Alleviates Non-alcoholic Fatty Liver Disease by Reducing Lipid Accumulation, Suppressing Inflammation and Oxidative Stress.

Limonin Alleviates Non-alcoholic Fatty Liver Disease by Reducing Lipid Accumulation, Suppressing Inflammation and Oxidative Stress.
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柠檬苦素通过减少脂质积累、抑制炎症和氧化应激来缓解非酒精性脂肪肝。

DOI:
10.3389/fphar.2021.801730
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发表时间:
2021
影响因子:
5.6
通讯作者:
Gao L
Gao L
中科院分区:
医学2区
文献类型:
--
作者:
Li Y;Yang M;Lin H;Yan W;Deng G;Ye H;Shi H;Wu C;Ma G;Xu S;Tan Q;Gao Z;Gao L

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非酒精性脂肪性肝病(NAFLD)是慢性肝病最常见的原因,在全球范围内持续上升。柠檬苦素是一种广泛存在于柑橘类植物果实中的三萜类化合物,具有广泛的药理作用,包括抗癌、抗炎、抗病毒、抗氧化和保肝作用。然而,柠檬苦素对斑马鱼NAFLD的潜在分子机制仍不清楚。采用硫代乙酰胺诱导斑马鱼幼鱼建立NAFLD模型,同时用柠檬苦素处理72 h。用脂质混合物刺激人肝细胞系,同时用柠檬苦素孵育24 h。结果表明,柠檬苦素可显著减少NAFLD大鼠肝脏中脂滴的积累,并下调脂肪生成转录因子FREBP和SREBP 1的水平。柠檬苦素抑制巨噬细胞浸润,下调巨噬细胞分泌的促炎因子IL-6、IL-1β和TNF-α的相对表达水平。此外,柠檬苦素可通过上调肝脏NRF 2/HO-1信号通路,逆转谷胱甘肽的还原和活性氧的积累。总之,这项研究表明,柠檬苦素对NAFLD具有保护作用,因为它具有抗脂质沉积以及抗氧化和抗炎作用。
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and continues to rise in the worldwide. Limonin is a triterpenoid compound widely found in the fruits of citrus plants with a wide range of pharmacological effects, including anti-cancer, anti-inflammation, anti-viral, anti-oxidation and liver protection properties. However, the potential molecular mechanism of limonin on NAFLD in zebrafish remains unknown. In this study, zebrafish larvae were exposed to thioacetamide to establish an NAFLD model and the larvae were treated with limonin for 72 h simultaneously. The human liver cell line was stimulated with lipid mixture and meanwhile incubated with limonin for 24 h. The results showed that Limonin significantly reduced the accumulation of lipid droplets in the liver and down-regulated the levels of lipogenic transcription factors FASN and SREBP1 in NAFLD. Limonin suppressed macrophages infiltration and the down-regulated the relative expression levels of the pro-inflammatory factors IL-6, IL-1β and TNF-α secreted by macrophages. Besides, limonin could reversed the reduction of glutathione and the accumulation of reactive oxygen species through up-regulating NRF2/HO-1 signaling pathway in the liver. In conclusion, this study revealed that limonin has a protective effect on NAFLD due to its resistance to lipid deposition as well as antioxidant and anti-inflammatory actions.
DOI: 10.1038/sigtrans.2017.23
发表时间: 2017
影响因子: 39.3
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DOI: 10.1080/03602532.2017.1293683
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