Kim Dong-Ha, Sim Yejin, Hwang Jin-Hyeon, Kwun In-Sook, Lim Jae-Hwan, Kim Jihoon, Kim Jee-In, Baek Moon-Chang, Akbar Mohammed, Seo Wonhyo, Kim Do-Kyun, Song Byoung-Joon, Cho Young-Eun
Department of Food and Nutrition, Andong National University, Andong 36729, Korea.
Department of Biological Science, Andong National University, Andong 36729, Korea.
Antioxidants (Basel). 2021 Aug 30;10(9):1386. doi: 10.3390/antiox10091386.
Alcoholic liver disease (ALD) is a major liver disease worldwide and can range from simple steatosis or inflammation to fibrosis/cirrhosis, possibly through leaky gut and systemic endotoxemia. Many patients with alcoholic steatohepatitis (ASH) die within 60 days after clinical diagnosis due to the lack of an approved drug, and thus, synthetic and/or dietary agents to prevent ASH and premature deaths are urgently needed. We recently reported that a pharmacologically high dose of pomegranate extract prevented binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Herein, we investigate whether a dietary antioxidant ellagic acid (EA) contained in many fruits, including pomegranate and vegetables, can protect against binge alcohol-induced leaky gut, endotoxemia, and liver inflammation. Pretreatment with a physiologically-relevant dose of EA for 14 days significantly reduced the binge alcohol-induced gut barrier dysfunction, endotoxemia, and inflammatory liver injury in mice by inhibiting gut dysbiosis and the elevated oxidative stress and apoptosis marker proteins. Pretreatment with EA significantly prevented the decreased amounts of gut tight junction/adherent junction proteins and the elevated gut leakiness in alcohol-exposed mice. Taken together, our results suggest that EA could be used as a dietary supplement for alcoholic hepatitis patients.
酒精性肝病（ALD）是全球主要的肝脏疾病，范围可从单纯脂肪变性或炎症到纤维化/肝硬化，可能是通过肠道屏障功能受损和全身性内毒素血症发展而来。许多酒精性脂肪性肝炎（ASH）患者在临床诊断后60天内死亡，原因是缺乏获批药物，因此，迫切需要合成和/或膳食制剂来预防ASH和过早死亡。我们最近报道，药理学高剂量的石榴提取物通过抑制氧化应激和硝化应激，预防了暴饮酒精引起的肠道屏障功能受损和肝脏炎症。在此，我们研究了许多水果（包括石榴）和蔬菜中含有的膳食抗氧化剂鞣花酸（EA）是否可以预防暴饮酒精引起的肠道屏障功能受损、内毒素血症和肝脏炎症。用生理相关剂量的EA预处理14天，通过抑制肠道菌群失调以及氧化应激和凋亡标志物蛋白的升高，显著减轻了暴饮酒精引起的小鼠肠道屏障功能障碍、内毒素血症和炎症性肝损伤。EA预处理显著预防了酒精暴露小鼠肠道紧密连接/黏附连接蛋白数量的减少以及肠道屏障功能受损的加剧。综上所述，我们的结果表明EA可作为酒精性肝炎患者的膳食补充剂。
