Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane.Dyspepsia and related problems with peptic ulcers linked to Helicobacter pylori are major problems in many parts of the world (37). H. pylori is a gram-negative, spiral-shaped bacterium that lives in the stomach and duodenum. By releasing an enzyme called "urease," H. pylori is able to survive in the stomach. Urease converts urea into ammonia, which then counters the stomach acid. This creates a neutralizing environment for protecting H. pylori from the acid in the stomach. Gastric infection with H. pylori may lead to the onset of various gastric-related diseases (13). Most patients specifically with duodenal ulcer can be cured by killing H. pylori with antibiotics and proton pump inhibitors (22, 29). In recent studies, H. pylori infection was also suspected to be associated with coronary artery and ischemic heart disease (4, 9, 21, 23). Many antibiotic-linked treatments have been recommended for eradication of H. pylori, but the emergence of antibiotic resistance makes the treatments more complicated, and the infection is sustained at higher levels when the drug treatment is stopped (12,29). Two common antibiotics used for treatment of H. pylori infection are metronidazole and clarithromycin. Several triple-or quadruple-antibiotic therapies with proton pump inhibitors have been shown to be effective in eradication of H. pylori (14), but no single treatment regimen is considered the final treatment of choice.Research has indicated that urease of H. pylori is located in the cytoplasm in freshly prepared cultures and in the outer membrane in older cultures (15). In addition to pathogenicity from H. pylori, evidence indicates that ammonia generated by urease can cause injury to the gastroduodenal mucosa (33, 42). Specific inhibition of urease activity has been proposed as a possible strategy to inhibit this microorganism (25). It has been demonstrated that a urease-negative mutant does not cause ga...