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.
Bibliographical noteFunding Information:
Funding: This study was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism. This work was also supported by the Bio & Medical Technology Development Program of the National Research Foundation of Korea (NRF) grants funded by the Korea government (Ministry of Science & ICT, MSIT) (2017M3A9G8083382), (No. 2019R1G1A109992111, 2021R1A4A1033078, and 2021R1C1C100811711), and a grant from 2019 Research Fund of Andong National University.
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
- Binge alcohol
- Ellagic acid
- Gut microbiota
- Inflammatory fatty liver injury
- Intestinal barrier dysfunction