NATURAL FLAVONOIDS IN GASTRIC MUCOSAL PROTECTION: FROM BENCH TO BEDSIDE

Gastric ulcer disease (GUD) continues to impose a substantial global health burden, arising from a disequilibrium between aggressive luminal factors—gastric acid, pepsin, Helicobacter pylori (H. pylori), non-steroidal anti-inflammatory drugs (NSAIDs), bile reflux, and reactive oxygen species (ROS)—and mucosal defense systems comprising mucus–bicarbonate secretion, prostaglandins, epithelial restitution, tight junction integrity, and mucosal blood flow. While proton pump inhibitors (PPIs) and H2 receptor antagonists remain the cornerstone of therapy, their long-term use is associated with adverse effects, drug–drug interactions, rebound hyperacidity, and recurrence. Consequently, there is growing interest in multi-targeted, safer alternatives. Flavonoids—ubiquitous plant-derived polyphenols—exhibit potent antioxidant, anti-inflammatory, antimicrobial, cytoprotective, and anti-secretory activities that converge on key ulcerogenic pathways. This review comprehensively synthesizes the chemistry and classification of flavonoids, gastric ulcer pathophysiology, and the molecular mechanisms underpinning flavonoid-mediated gastroprotection, including redox homeostasis, NF-κB/MAPK modulation, prostaglandin biosynthesis, nitric oxide (NO) signaling, mucin regulation, and H. pylori inhibition. It further evaluates pharmacokinetics and bioavailability constraints, and outlines advanced formulation strategies (nanoparticles, liposomes, solid dispersions, and gastroretentive systems) to enhance therapeutic performance. Preclinical and emerging clinical evidence are critically appraised, and future perspectives for translation, standardization, and regulatory alignment are discussed. Flavonoids represent promising, multi-modal candidates for next-generation anti-ulcer therapeutics.

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