Non-Classical Therapeutic Approaches in Gastric Ulcer: A Comprehensive Review of Pathophysiology, Epidemiology, Experimental Models, and Diagnosis

Gastric ulcer (GU) remains a significant global health concern, characterized by mucosal disruption in the stomach lining that penetrates the muscularis mucosae and typically exceeds 5 mm in diameter. This review provides an in-depth examination of the multifactorial pathophysiology of GU, focusing on the imbalance between aggressive factors, such as gastric acid, pepsin, and Helicobacter pylori (H. pylori) infection, and protective mechanisms, including mucus secretion, bicarbonate production, and mucosal blood flow. Epidemiological trends highlight the persistent burden of GU, particularly in populations with high non-steroidal anti-inflammatory drug (NSAID) consumption and H. pylori prevalence. Experimental models, ranging from pylorus ligation-induced ulcers to NSAID-based protocols, provide valuable insights into ulcer development and therapeutic evaluation. Advances in diagnostic techniques, including endoscopy and biomarker analysis, have enhanced clinical detection and monitoring. In addition to classical therapeutic approaches, this review highlights the emerging role of non-classical and repurposed drugs, such as dimethyl fumarate (DMF), liraglutide, and nifuroxazide (NIF), in ulcer management. By integrating insights from recent experimental studies, this review underlines the therapeutic potential of these unconventional strategies and recommends further translational research to optimize ulcer management.