EXPLORING ELLAGIC ACID AS A HEPATOPROTECTIVE AGENT: FROM MECHANISTIC PATHWAYS TO THERAPEUTIC APPLICATIONS

Ellagic acid (EA), a naturally occurring polyphenolic compound found in various fruits and nuts, has emerged as a promising hepatoprotective agent due to its potent antioxidant, anti-inflammatory, antifibrotic, and anticancer properties. Chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), fibrosis, and hepatocellular carcinoma are driven by oxidative stress, inflammation, mitochondrial dysfunction, and hepatocyte apoptosis. EA exerts hepatoprotective effects by scavenging reactive oxygen species (ROS), upregulating Nrf2/HO-1 signaling, suppressing NF-κB-mediated inflammation, stabilizing mitochondrial membranes, and modulating apoptosis pathways. However, EA's poor water solubility, limited gastrointestinal absorption, and rapid metabolism severely restrict its bioavailability. Recent advancements in Nano nanoformulations, such as liposomes, phytosomes, and nanoparticles, have shown promise in improving its pharmacokinetic profile. Moreover, gut microbiota-derived metabolites, particularly urolithin A, are believed to mediate many of EA’s systemic effects, although interindividual variability in microbial composition influences therapeutic outcomes. In addition to its hepatoprotective activity, EA demonstrates anticancer potential by targeting cell cycle regulators and pro-survival pathways, and offers dermatoprotective benefits through photo protection, anti-tyrosinase activity, and wound healing enhancement. While preclinical studies consistently validate EA’s efficacy, further clinical trials and microbiome-personalized approaches are essential to fully translate its potential into therapeutic application. This review comprehensively explores the pharmacological mechanisms, bioavailability challenges, and future directions for EA in liver disease and beyond.