Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice
Fucoxanthin inhibits hepatic oxidative stress, inflammation, and fibrosis in diet-induced nonalcoholic steatohepatitis model mice
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DOI：
10.1016/j.bbrc.2020.05.050
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发表时间：
2020-07-23
影响因子：
3.1
通讯作者：
Hosokawa, Masashi
中科院分区：
文献类型：
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作者：
Takatani, Naoki;Kono, Yuka;Hosokawa, Masashi
非酒精性脂肪性肝炎（NASH）与肝细胞损伤、过度氧化应激和脂肪肝中的慢性炎症相关，并且可以进展为更严重的肝脏疾病，如肝硬化和肝细胞癌。然而，目前还没有针对NASH的有效疗法。海洋类胡萝卜素岩藻黄素（fucoxanthin，Fx）广泛存在于褐藻中，具有抗癌、抗炎、抗氧化、抗肥胖等多种生物活性。然而，Fx对NASH发展的影响尚未研究。我们研究了Fx在饮食诱导的NASH模型小鼠中的保护作用，所述小鼠喂食胆碱缺乏L-氨基酸限定的高脂饮食（CDAHFD）。Fx给药显著减弱了肝脏重量增加和肝脏脂肪积累，导致肝损伤减轻。此外，与CDAHFD喂养的小鼠相比，Fx喂养的小鼠不仅表现出降低的肝脏脂质氧化，而且还降低了炎症和浸润相关基因的mRNA表达水平。此外，岩藻黄素和苦杏仁黄质A，两个Fx代谢产物发挥抗炎作用，在肝脏中通过抑制肝细胞中的趋化因子的产生。在纤维化的情况下，晚期NASH的特征之一，纤维化因子的表达，包括活化的肝星状细胞标志物，在Fx喂养的小鼠的肝脏中显著降低。因此，本研究阐明，膳食Fx不仅抑制肝脏氧化应激和炎症，而且还预防饮食诱导的NASH模型小鼠的早期纤维化。(C)2020爱思唯尔公司All rights reserved.
Nonalcoholic steatohepatitis (NASH) is associated with hepatocyte injury, excessive oxidative stress, and chronic inflammation in fatty liver, and can progress to more severe liver diseases, such as cirrhosis and hepatocellular carcinoma. However, currently there are no effective therapies for NASH. Marine carotenoid, fucoxanthin (Fx), abundant in brown seaweeds, has variable biological properties, such as anticancer, anti-inflammatory, anti-oxidative and anti-obesity. However, the effect of Fx on the development of NASH has not been explored. We investigated the protective effects of Fx in diet-induced NASH model mice fed choline-deficient L-amino acid-defined high fat diet (CDAHFD). Fx administration significantly attenuated liver weight gain and hepatic fat accumulation, resulting in the alleviation of hepatic injury. Furthermore, the Fx-fed mice, not only exhibited reduced hepatic lipid oxidation, but also decreased mRNA expression levels of inflammation and infiltration-related genes compared to that of the CDAHFD-fed mice. Moreover, fucoxanthinol and amarouciaxanthin A, two Fx metabolites exerted anti-inflammatory effects in the liver via inhibiting the chemokine production in hepatocytes. In case of fibrosis, one of the features of advanced NASH, the expression of fibrogenic factors including activatedhepatic stellate cell marker was significantly decreased in the liver of Fx-fed mice. Thus, the present study elucidated that dietary Fx not only inhibited hepatic oxidative stress and inflammation but also prevented early phase of fibrosis in the diet-induced NASH model mice. (C) 2020 Elsevier Inc. All rights reserved.