Ellagic Acid Prevents Binge Alcohol-Induced Leaky Gut and Liver Injury through Inhibiting Gut Dysbiosis and Oxidative Stress
Dong-ha Kim,
Yejin Sim,
Jin-hyeon Hwang,
In-Sook Kwun,
Jae-Hwan Lim,
Jihoon Kim,
Jee-In Kim,
Moon-Chang Baek,
Mohammed Akbar,
Wonhyo Seo,
Do-Kyun Kim,
Byoung-Joon Song,
Young-Eun Cho
Affiliations
Dong-ha Kim
Department of Food and Nutrition, Andong National University, Andong 36729, Korea
Yejin Sim
Department of Food and Nutrition, Andong National University, Andong 36729, Korea
Jin-hyeon Hwang
Department of Food and Nutrition, Andong National University, Andong 36729, Korea
In-Sook Kwun
Department of Food and Nutrition, Andong National University, Andong 36729, Korea
Jae-Hwan Lim
Department of Biological Science, Andong National University, Andong 36729, Korea
Jihoon Kim
Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA
Jee-In Kim
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 41944, Korea
Moon-Chang Baek
Department of Molecular Medicine, School of Medicine, Cell & Matrix Research Institute, Kyungpook National University, Daegu 41944, Korea
Mohammed Akbar
Division of Neuroscience and Behavior, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA
Wonhyo Seo
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea
Do-Kyun Kim
Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Korea
Byoung-Joon Song
Section of Molecular Pharmacology and Toxicology, Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Bethesda, Bethesda, MD 20892, USA
Young-Eun Cho
Department of Food and Nutrition, Andong National University, Andong 36729, Korea
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.