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.