Isochlorogenic Acid C and <i>Artemisia argyi</i> Extract Prevent Acute Gastritis by Mitigating Gastric Mucosa Injury and Mitochondrial Dysfunction

Gastritis is a common inflammatory gastrointestinal disease affecting approximately 40% of the global population. Alcohol abuse is a major contributor to gastritis, primarily acting through gastric mucosal injury and inflammation. Given the association between alcohol consumption and severe gastrointestinal complications, safe and effective strategies for the prevention and treatment of gastritis are urgently needed. This study investigated the pathophysiological effects of ethanol (EtOH) on gastric tissues using an EtOH-HCl-treated acute gastritis mouse model, EtOH-treated AGS gastric epithelial cells, and LPS-treated RAW 264.7 macrophages. We found that EtOH induces acute gastritis by damaging the gastric mucosa, elevating oxidative stress, and disrupting mitochondrial function. We identified Isochlorogenic acid C (ICAC) as a promising therapeutic candidate to counteract these detrimental effects. In the mouse model, oral administration of ICAC significantly alleviated acute gastritis by preserving mucosal integrity, preventing prostaglandin E₂ depletion, and enhancing <i>Ptgs1</i> and <i>Muc6</i> expression in mice, while suppressing inflammatory mediator production in gastric tissues. Mechanistically, ICAC's preventive effects in human cells manifested through <i>PTGS1</i> upregulation and the inhibition of inflammatory pathways in AGS cells. Interestingly, ICAC mitigated mitochondrial dysfunction by modulating calcium-mediated mitochondrial fission, reducing mitochondrial reactive oxygen species production, stabilizing mitochondrial membrane potential, and maintaining mitochondrial morphology. Furthermore, the ethanol extract of <i>Artemisia argyi</i>, which is composed primarily of ICAC, exhibited comparable protective effects. These findings highlight the detrimental impacts of alcohol on gastric health and identify ICAC as a potential nutraceutical agent for the prevention and treatment of acute gastritis.