Piceatannol, a Natural Polyphenol From Grape, Inhibits <i>Helicobacter pylori</i> Through Targeted Suppression of Its Secreted Urease

<i>Helicobacter pylori</i> infection, mediated largely through its urease enzyme, causes chronic gastric inflammation that can progress to severe pathology. This study investigates the inhibitory effects of piceatannol (PIC), a polyphenol from grape peels, on <i>H. pylori</i> growth and its urease activity. PIC remarkably inhibited the growth of three <i>H. pylori</i> strains, with MIC values ranging from 100 to 150 μg/mL. Furthermore, PIC exerted a potent inhibitory effect on <i>H. pylori</i> urease (HPU) and jack bean urease (JBU) with IC₅₀ values of 0.67 ± 0.02 mM and 0.47 ± 0.01 mM, respectively. Kinetic studies revealed that PIC acts as a slow-binding, mixed inhibitor of HPU and a slow-binding, non-competitive inhibitor for JBU. The use of thiol-blocking substances observably delayed the deactivation of HPU and JBU, whereas the synergistic effect of PIC with competitive inhibitors of Ni²⁺ further restrained urease activity. These results indicated that the sulfhydryl group in the active site may be the key binding site for PIC to inhibit HPU and JBU. Molecular docking simulations further support the inhibitory mechanism. Additionally, the inactivation of HPU and JBU caused by PIC was reversible. In conclusion, PIC significantly suppresses the growth of <i>H. pylori</i> and the activity of its major virulence factor, urease. Further investigation into the kinetic properties and mechanisms revealed that the inhibition of urease by PIC may target the active site sulfhydryl group.