Ellagic Acid Promotes Repair of Acetic Acid-Induced Oral Ulcers in Rats: Associations with Redox-Inflammatory Responses and STAT3/EGFR Signaling

Oxidative stress and inflammation are central barriers to oral mucosal ulcer repair, yet redox-oriented interventions for recurrent aphthous ulcer (RAU)-relevant injury remain insufficiently defined. Ellagic acid (EA) is a naturally occurring polyphenol with antioxidant and anti-inflammatory activities, but its role in oral mucosal repair and the associated signaling events require further characterization. Here, EA was selected from serum-exposed constituents of Yumai Kouyan Heji (YMKY) and evaluated using computational target prioritization, a rat model of acetic acid-induced oral ulcers, and H2O2-injured human oral keratinocytes. Network and molecular analyses identified STAT3 and EGFR as putative targets for further investigation. In vivo, EA accelerated ulcer closure, improved epithelial integrity and collagen organization, improved serum antioxidant indices, reduced serum MDA and inflammatory cytokine levels, and attenuated apoptosis. EA also reduced injury-associated phosphorylation of STAT3 and EGFR in ulcer tissues. In vitro, EA improved cell viability and migration-assay outcomes in H2O2-injured human oral keratinocytes, reduced DCF fluorescence and inflammatory responses, preserved mitochondrial membrane potential, reduced apoptosis, and regulated STAT3/EGFR phosphorylation together with Bax/Bcl-2 expression. These findings support the repair-promoting activity of EA in experimental oral mucosal injury, accompanied by improved redox-inflammatory indices and altered STAT3/EGFR signaling. The causal involvement of these pathways and the applicability of the findings to human RAU remain to be established.