Discovery of Gingipains and Inhibitors from Food-Derived Natural Products: A Narrative Review.

is a key periodontal pathogen whose cysteine proteases, gingipains (Rgp and KGP), are essential for nutrient acquisition and virulence. Targeting gingipains may attenuate bacterial pathogenicity and prevent related systemic diseases. This paper aimed to review advances in food-derived natural products that inhibit or gingipains, with emphasis on mechanisms, potency, and translational potential. A literature search of several databases identified 64 studies on food-derived compounds demonstrating in vitro, in vivo, or clinical effects against or gingipains. The results showed that tea polyphenols and dihydrochalcones (e.g., phloretin and phlorizin) inhibited gingipain activity, and a variety of food-derived natural products (especially polyphenols and polysaccharides) suppressed the growth, survival, biofilm formation, and virulence of . Structure-activity relationships suggest galloyl moieties and dihydrochalcone scaffolds enhance gingipain inhibition. Polysaccharides and alkaloids exhibited anti-adhesion or protease inhibition, though with limited potency data. In summary, food-derived natural products represent promising gingipain inhibitors. These inhibitors have potential structure-activity relationships, indicating that food-derived natural products have considerable research prospects. Future research should prioritize structure-based discovery and structure optimization to realize their therapeutic potential.