Abstract
Helicobacter pylori (H. pylori), one of the most common infectious pathogens in the world, can cause gastritis, digestive ulcers, and even gastric cancer. H. pylori urease (HPU) is a distinctive virulence factor of H. pylori that allows it to be distinguished from other pathogens. Dried ginger is a famous edible and medicinal herb that is commonly used to prevent and treat gastrointestinal tract-related diseases. In this study, phytochemical analysis of the aqueous extract of dried ginger (DGE) and the inhibition of DGE on H. pylori was investigated. Subsequently, we evaluated the inhibitory activity of DGE against enzymes including HPU and jack bean urease (JBU) and determined its potential mechanism of action. UPLC-ESI-MS/MS analysis indicated that a total of 63 compounds including seven glycosides, nine terpenoids, two esters, seven phenols, eight lignans, five phenylpropanoids, and four phenolic acids were identified in DGE. DGE was observed to inhibit the growth of four H. pylori strains (ATCC 43504, NCTC 26695, SS1, and ICDC 111001) with minimum inhibitory concentration (MIC) values spanning the range of 0.05 to 1.50 mg mL-1. Moreover, DGE has higher enzyme inhibitory activity on HPU (IC50 = 0.49 ± 0.01 mg mL-1) than on JBU (IC50 = 0.54 ± 0.01 mg mL-1). Enzyme inhibitory kinetic analysis revealed that the inhibition type of DGE against HPU was slow-binding and anti-competitive, whereas it was slow-binding and mixed type on JBU. A further mechanism study indicated that the protective effect of sulfhydryl-containing compounds on enzyme activity was significantly better than that of inorganic compounds, indicating that the action site of DGE inhibition of enzyme was the sulfhydryl residue. The results of DTT reactivation experiments showed that the DGE-urease complex was reversible. Furthermore, molecular docking investigation showed that the main components of DGE interacted with sulfhydryl groups and Ni2+. In conclusion, DGE effectively inhibited the growth of H. pylori and the activity of its key virulence factor urease. And the in-depth study of the kinetic characteristics and the mechanism of action showed that the active site sulfhydryl group and Ni2+ might be the targets of urease inhibition by DGE. Our study may provide experimental evidence for the traditional application of dried ginger in the treatment of H. pylori-associated gastric diseases.
Published Version
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