<i>Sicyos angulatus</i> Protects Against Binge-Drinking Alcohol-Induced Liver Injury by Preserving the Intestinal Barrier Integrity

Alcoholic liver injury (ALI) is a prevalent and severe form of liver disease that lacks specific therapies, relying instead on supportive care. In ALI, gut epithelial tight junction proteins are compromised, leading to increased intestinal permeability and the translocation of endotoxins, such as lipopolysaccharides (LPS), into the bloodstream, thereby aggravating liver injury. The plant <i>Sicyos angulatus</i> (SA), part of the <i>Cucurbitaceae</i> family, is recognized for its anti-inflammatory and antioxidant effects but has not yet been studied for potential efficacy in mitigating ALI. In this study, we induced ALI in mice by administering high oral doses of ethanol following pretreatment with or without SA. The SA-treated mice exhibited significantly lower levels of plasma alanine aminotransferase and aspartate aminotransferase, markers indicative of reduced liver damage. Despite observing no notable changes in hepatic fat accumulation or expression of alcohol metabolism-related genes, we found that the SA group exhibited a marked reduction in terminal transferase dUTP nick end labeling-positive hepatocytes and reactive oxygen species within the mitochondrial fraction of liver tissue. Additionally, SA preserved intestinal barrier integrity by upregulating genes associated with tight junctions in the ileum and colon, resulting in lower LPS levels in the blood. Complementary <i>in vitro</i> studies with Caco-2 cells further showed that SA pretreatment protected against LPS-induced tight junction disruption by inhibiting NF-κB pathway activation. Collectively, our findings indicate that SA protects against ALI by supporting gut barrier integrity, thereby limiting LPS translocation and hepatic oxidative stress. This study underscores the potential of SA as a therapeutic agent targeting the gut-liver axis.