Inhibition of Helicobacter pylori and Associated Urease by Oregano and Cranberry Phytochemical Synergies

Department of Food Science, Chenoweth Laboratory, University of Massachusetts, Amherst, MA 01003, USA.
Applied and Environmental Microbiology (Impact Factor: 3.67). 01/2006; 71(12):8558-64. DOI: 10.1128/AEM.71.12.8558-8564.2005
Source: PubMed


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.

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    • "Phenolic compounds are able to damage the cell membrane and thus increase permeability (Hendry and others 2009). They also may interfere with electron transport chain along the bacterial membrane and inhibit dehydrogenase-linked proton efflux such as proline dehydrogenase (Lin and others 2005). These data may "
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    • "saprophyticus (protein Q4A0J5, the alpha subunit encoded by SSP0263 or ureC; protein Q4A0J4, the beta subunit encoded by SSP0254 or ureB; and protein Q4A0J3, the gamma subunit encoded by SSP0265 or ureA) indicate that these proteins do not contain cysteine residues (Sch€ afer and Kaltwasser 1994; Kuroda et al. 2005). Extracts of various plants including green tea and cranberries often have been used to treat gastritis or urinary tract infections because they contain urease inhibitors (Matsubara et al. 2003; Lin et al. 2005). Urease activity from Staph. "
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    ABSTRACT: Unlabelled: Urease is a virulence factor for the Gram-positive urinary tract pathogen Staphylococcus saprophyticus. The susceptibility of this enzyme to chemical inhibition was determined using soluble extracts of Staph. saprophyticus strain ATCC 15305. Acetohydroxamic acid (Ki = 8.2 μg ml(-1) = 0.106 mmol l(-1) ) and DL-phenylalanine hydroxamic acid (Ki = 21 μg ml(-1) = 0.116 mmol l(-1) ) inhibited urease activity competitively. The phosphorodiamidate fluorofamide also caused competitive inhibition (Ki = 0.12 μg ml(-1) = 0.553 μmol l(-1) = 0.000553 mmol l(-1) ), but the imidazole omeprazole had no effect. Two flavonoids found in green tea extract [(+)-catechin hydrate (Ki = 357 μg ml(-1) = 1.23 mmol l(-1) ) and (-)-epigallocatechin gallate (Ki = 210 μg ml(-1) = 0.460 mmol l(-1) )] gave mixed inhibition. Acetohydroxamic acid, DL-phenylalanine hydroxamic acid, fluorofamide, (+)-catechin hydrate and (-)-epigallocatechin gallate also inhibited urease activity in whole cells of strains ATCC 15305, ATCC 35552 and ATCC 49907 grown in a rich medium or an artificial urine medium. Addition of acetohydroxamic acid or fluorofamide to cultures of Staph. saprophyticus in an artificial urine medium delayed the increase in pH that normally occurs during growth. These results suggest that urease inhibitors may be useful for treating urinary tract infections caused by Staph. saprophyticus. Significance and impact of the study: The enzyme urease is a virulence factor for the Gram-positive urinary tract pathogen Staphylococcus saprophyticus. We have shown that urease activity in cell-free extracts and whole bacterial cells is susceptible to inhibition by hydroxamates, phosphorodiamidates and flavonoids, but not by imidazoles. Acetohydroxamic acid and fluorofamide in particular can temporarily delay the increase in pH that occurs when Staph. saprophyticus is grown in an artificial urine medium. These results suggest that urease inhibitors may be useful as chemotherapeutic agents for the treatment of urinary tract infections caused by this micro-organism.
    Letters in Applied Microbiology 09/2013; 58(1). DOI:10.1111/lam.12153 · 1.66 Impact Factor
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    • "Berries, including raspberries, blueberries, black currants, red currants, and cranberries, are a rich source of these dietary antioxidants [1]. The American cranberry (Vaccinium macrocarpon) in particular is a rich source of bioactive compounds with antiproliferative , antioxidant [2], anti-inflammatory and antimicrobial properties, which inhibit the growth of pathogenic bacteria such as Escherichia coli and Helicobacter pylori for example [3] [4]. It has traditionally been used in the treatment and prevention of urinary-tract infections in women and also in digestive-tract ailments. "
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    ABSTRACT: The phenolic fraction of a commercial cranberry syrup, which is purported to have good properties for the prevention of urinary diseases, has been thoroughly characterized using HPLC-DAD–TOF-MS. A study of its antibacterial activity has also been carried out. For this purpose a new HPLC-DAD–TOF-MS method using negative and positive ionization modes was developed and it was thus possible to identify 34 different compounds, nine of which have been tentatively characterized for the first time in cranberry syrup. It is also important to highlight that different coumarins in this matrix were also determined, which, to our knowledge, have not been found previously in the cranberry. The phenolic fraction obtained by HPLC-DAD was found to be 5.47 mg/mL. Catechin and procyanidins belonging to flavanols were the family of compounds found at the highest concentrations (2.37 mg/mL); flavonols were at a concentration of 1.91 mg/mL and phenolic-acid derivatives were found at the lowest concentration (0.15 mg/mL). With regard to antibacterial activity, the incubation of Escherichia coli with cranberry syrup was found to reduce surface hydrophobicity as a function of the concentration of the extract.
    Journal of Pharmaceutical and Biomedical Analysis 01/2012; 58(1):34-41. DOI:10.1016/j.jpba.2011.09.027 · 2.98 Impact Factor
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