In Vitro and In Vivo Activities of Tea Catechins against Helicobacter pylori

ABSTRACT The catechin epigallocatechin gallate showed the strongest activity of the six tea catechins tested against Helicobacter pylori(MIC for 50% of the strains tested, 8 μg/ml). It had bactericidal activity at pH 7 but not at pH ≤5.0. In infected Mongolian gerbils,H. pylori was eradicated in 10 to 36% of the catechin-treated animals, with significant decreases in mucosal hemorrhage and erosion. Tea catechins, therefore, may have therapeutic effects on H. pylori infection.

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Therapeutic effects of Zuojin Pill on Helicobacter pylori-induced chronic atrophic gastritis through JMJD2B/COX-2/VEGF signaling axis

10.21203/rs.3.rs-20652/v2 ◽

2020 ◽

Author(s):

Shihua Wu ◽

Chunmei Bao ◽

Ruilin Wang ◽

Xiaomei Zhang ◽

Sijia Gao ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cell Viability ◽

Atrophic Gastritis ◽

Chronic Atrophic Gastritis ◽

Gastric Mucosal Damage ◽

Therapeutic Effects ◽

Cox 2 ◽

H Pylori

Abstract Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG. Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.

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Hydrogen Peroxide-Mediated Oxygen Enrichment Eradicates Helicobacter pylori In Vitro and In Vivo

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02192-19 ◽

2020 ◽

Vol 64 (5) ◽

Author(s):

Jia Di ◽

Jun Zhang ◽

Lei Cao ◽

Ting-ting Huang ◽

Jun-xia Zhang ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Helicobacter Pylori ◽

Bacterial Cell ◽

Cell Membranes ◽

Enriched Environment ◽

Mongolian Gerbils ◽

Content Type ◽

H Pylori

ABSTRACT Helicobacter pylori is an important risk factor for gastric ulcers. However, antibacterial therapies increase the resistance rate and decrease the eradication rate of H. pylori. Inspired by the microaerophilic characteristics of H. pylori, we aimed at effectively establishing an oxygen-enriched environment to eradicate and prevent the recurrence of H. pylori. The effect and the mechanism of an oxygen-enriched environment in eradicating H. pylori and preventing the recurrence were explored in vitro and in vivo. During oral administration and after drug withdrawal, H. pylori counts were evaluated by Giemsa staining in animal cohorts. An oxygen-enriched environment in which H. pylori could not survive was successfully established by adding hydrogen peroxide into several solutions and rabbit gastric juice. Hydrogen peroxide effectively killed H. pylori in Columbia blood agar and special peptone broth. Minimum inhibition concentrations and minimum bactericidal concentrations of hydrogen peroxide were both relatively stable after promotion of resistance for 30 generations, indicating that hydrogen peroxide did not easily promote resistance in H. pylori. In models of Mongolian gerbils and Kunming mice, hydrogen peroxide has been shown to significantly eradicate and effectively prevent the recurrence of H. pylori without toxicity and damage to the gastric mucosa. The mechanism of hydrogen peroxide causing H. pylori death was related to the disruption of bacterial cell membranes. The oxygen-enriched environment achieved by hydrogen peroxide eradicates and prevents the recurrence of H. pylori by damaging bacterial cell membranes. Hydrogen peroxide thus provides an attractive candidate for anti-H. pylori treatment.

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Helicobacter pylori Eradication by Sitafloxacin-Lansoprazole Combination and Sitafloxacin Pharmacokinetics in Mongolian Gerbils and ItsIn VitroActivity and Resistance Development

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01105-10 ◽

2011 ◽

Vol 55 (9) ◽

pp. 4261-4266 ◽

Cited By ~ 4

Author(s):

Tatsuo Yamamoto ◽

Tomomi Takano ◽

Wataru Higuchi ◽

Akihito Nishiyama ◽

Ikue Taneike ◽

...

Keyword(s):

Helicobacter Pylori ◽

Antimicrobial Agents ◽

Therapeutic Effects ◽

Mongolian Gerbils ◽

Maximum Serum ◽

Resistance Development ◽

Content Type ◽

Maximum Serum Concentration ◽

H Pylori

ABSTRACTA total of 293 strains ofHelicobacter pylori, including strains resistant to levofloxacin, clarithromycin, metronidazole, or amoxicillin, were examined forin vitrosusceptibility to 10 antimicrobial agents. Among these agents, sitafloxacin (a fluoroquinolone) showed the greatest activity (MIC90, 0.06 μg/ml), with high bactericidal activity and synergy in sitafloxacin-lansoprazole (a proton pump inhibitor) combination. In a Mongolian gerbil model with aH. pyloriATCC 43504 challenge, marked eradication effects were observed at ≥1 mg/kg for sitafloxacin, ≥10 mg/kg for levofloxacin, and ≥10 mg/kg for lansoprazole, reflecting MIC levels for each agent (0.008, 0.25, and 2 μg/ml, respectively). The therapeutic rates were 83.3% for the sitafloxacin (0.3 mg/kg)-lansoprazole (2.5 mg/kg) combination and 0% for either sitafloxacin or lansoprazole alone. The maximum serum concentration (Cmax) of sitafloxacin was 0.080 ± 0.054 μg/ml at 30 min, when orally administered at 1 mg/kg. The simultaneous administration of lansoprazole resulted in no difference. In the resistance development assay, MICs of levofloxacin increased 64- to 256-fold withgyrAmutations (Ala88Pro and Asn87Lys), while MICs of sitafloxacin only up to 16-fold with the Asn87Lys mutation. The data suggest that sitafloxacin exhibited superior anti-H. pyloriactivity with low rates of resistance developmentin vitroand that, reflecting highin vitroactivities, sitafloxacin-lansoprazole combination exhibited strong therapeutic effects in Mongolian gerbils with aCmaxof sitafloxacin that was 10-fold higher than the MIC value at a 1-mg/kg administration.

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Rapid Loss of Motility of Helicobacter pylori in the Gastric Lumen In Vivo

Infection and Immunity ◽

10.1128/iai.73.3.1584-1589.2005 ◽

2005 ◽

Vol 73 (3) ◽

pp. 1584-1589 ◽

Cited By ~ 42

Author(s):

Sören Schreiber ◽

Roland Bücker ◽

Claudia Groll ◽

Marina Azevedo-Vethacke ◽

Désirée Garten ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Juice ◽

Mongolian Gerbils ◽

Gastric Mucus ◽

Ph Values ◽

Short Period ◽

Gastric Lumen ◽

H Pylori

ABSTRACT The human pathogen Helicobacter pylori has infected more than half of the world's population. Nevertheless, the first step of infection, the acute colonization of the gastric mucus, is poorly understood. For successful colonization, H. pylori must retain active motility in the gastric lumen until it reaches the safety of the mucus layer. To identify the factors determining the acute colonization, we inserted bacteria into the stomach of anesthetized Mongolian gerbils. We adjusted the gastric juice to defined pH values of between 2.0 and 6.0 by using an autotitrator. Despite the fact that Helicobacter spp. are known to survive low pH values for a certain time in vitro, the length of time that H. pylori persisted under the assay conditions within the gastric juice in vivo was remarkably shorter. In the anesthetized animal we found H. pylori to be irreversibly immotile in less than 1 min at lumen pH values of 2 and 3. At pH 4 motility was lost after 2 min. However, the period of motility increased to more than 15 min at pH 6. Blocking pepsins in the gastric lumen in vivo by using pepstatin significantly increased the period of motility. It was possible to simulate the rapid in vivo immotilization in vitro by adding pepsins. We conclude that pepsin limits the persistence of H. pylori in the gastric chymus to only a few minutes by rapidly inhibiting active motility. It is therefore likely that this short period of resistance in the gastric lumen is one of the most critical phases of Helicobacter infection.

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Therapeutic effect of Zuojin Pill on chronic atrophic gastritis induced by Helicobacter pylori through JMJD2B/COX-2/VEGF

10.21203/rs.3.rs-20652/v3 ◽

2020 ◽

Author(s):

Shihua Wu ◽

Chunmei Bao ◽

Ruilin Wang ◽

Xiaomei Zhang ◽

Sijia Gao ◽

...

Keyword(s):

Helicobacter Pylori ◽

Cell Viability ◽

Atrophic Gastritis ◽

Chronic Atrophic Gastritis ◽

Gastric Mucosal Damage ◽

Therapeutic Effects ◽

Cox 2 ◽

H Pylori

Abstract Background: Zuojin Pill (ZJP), a famous Chinese medicinal formula, is widely accepted for treatment of chronic atrophic gastritis (CAG) in China. This study aimed to explore the therapeutic effects and mechanisms of ZJP in Helicobacter pylori (H. pylori) - induced chronic atrophic gastritis (CAG) in vivo and in vitro. Methods: CAG rat model was induced by H. pylori. ZJP (0.63, 1.26, and 2.52 g/kg, respectively) was administered orally for four weeks. Therapeutic effects of ZJP were identified by H&E staining and serum indices. In addition, cell viability, morphology and proliferation were detected by cell counting kit-8 (CCK8) and high-content screening assay (HCS), respectively. Moreover, relative mRNA expression and protein expression related to JMJD2B/COX-2/VEGF axis was detected to investigate the potential mechanisms of ZJP in CAG.Results: Results showed the symptoms (weight loss and gastric mucosa damage) of CAG were alleviated, and the contents of TNF-α in serum was markedly decreased after treating with ZJP. Moreover, cell viability, proliferation and morphology changes of GES-1 cells were ameliorated by ZJP intervention. In addition, proinflammatory genes and JMJD2B/COX-2/VEGF axis related genes were suppressed by ZJP administration in vitro and in vivo. Meanwhile, immunohistochemistry (IHC) and western blot confirmed down-regulation of these genes by ZJP intervention. Conclusion: ZJP treatment can alleviate gastric mucosal damage induced by H. pylori via JMJD2B/COX-2/VEGF axis.

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The Oligo-Acyl Lysyl Antimicrobial Peptide C12K-2β12Exhibits a Dual Mechanism of Action and Demonstrates StrongIn VivoEfficacy against Helicobacter pylori

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00689-11 ◽

2011 ◽

Vol 56 (1) ◽

pp. 378-390 ◽

Cited By ~ 20

Author(s):

Morris O. Makobongo ◽

Hanan Gancz ◽

Beth M. Carpenter ◽

Dennis P. McDaniel ◽

D. Scott Merrell

Keyword(s):

Helicobacter Pylori ◽

Mechanism Of Action ◽

Mongolian Gerbils ◽

Nucleic Acid Binding ◽

Western Blots ◽

Content Type ◽

Bacterial Membranes ◽

H Pylori

ABSTRACTHelicobacter pylorihas developed antimicrobial resistance to virtually all current antibiotics. Thus, there is a pressing need to develop new anti-H. pyloritherapies. We recently described a novel oligo-acyl-lysyl (OAK) antimicrobial peptidomimetic, C12K-2β12, that shows potentin vitrobactericidal activity againstH. pylori. Herein, we define the mechanism of action and evaluate thein vivoefficacy of C12K-2β12againstH. pyloriafter experimental infection of Mongolian gerbils. We demonstrate using a 1-N-phenylnaphthylamine (fluorescent probe) uptake assay and electron microscopy that C12K-2β12rapidly permeabilizes the bacterial membrane and creates pores that cause bacterial cell lysis. Furthermore, using nucleic acid binding assays, Western blots, and confocal microscopy, we show that C12K-2β12can cross the bacterial membranes into the cytoplasm and tightly bind to bacterial DNA, RNA, and proteins, a property that may result in inhibition of enzymatic activities and macromolecule synthesis. To define thein vivoefficacy of C12K-2β12,H. pylori-infected gerbils were orogastrically treated with increasing doses and concentrations of C12K-2β121 day or 1 week postinfection. The efficacy of C12K-2β12was strongest in animals that received the largest number of doses at the highest concentration, indicating dose-dependent activity of the peptide (P< 0.001 by analysis of variance [ANOVA]) regardless of the timing of the treatment with C12K-2β12. Overall, our results demonstrate a dual mode of action of C12K-2β12against theH. pylorimembrane and cytoplasmic components. Moreover, and consistent with the previously reportedin vitroefficacy, C12K-2β12shows significantin vivoefficacy againstH. pyloriwhen used as monotherapy. Therefore, OAK peptides may be a valuable resource for therapeutic treatment ofH. pyloriinfection.

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Enhanced fitness of a Helicobacter pylori babA mutant in a murine model

Infection and Immunity ◽

10.1128/iai.00725-20 ◽

2021 ◽

Author(s):

M. Lorena Harvey ◽

Aung Soe Lin ◽

Lili Sun ◽

Tatsuki Koyama ◽

Jennifer H. B. Shuman ◽

...

Keyword(s):

Helicobacter Pylori ◽

Outer Membrane Proteins ◽

Population Diversity ◽

Fitness Advantage ◽

Neutral Locus ◽

Mutant Strains ◽

Bacterial Fitness ◽

H Pylori

Helicobacter pylori genomes encode >60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify hop mutant strains that exhibit altered fitness in vivo compared to fitness in vitro , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H. pylori strains within a mixed population. We generated a library of hop mutant strains, each containing a unique nucleotide barcode, as well as a library of control strains, each containing a nucleotide barcode in an intergenic region predicted to be a neutral locus unrelated to bacterial fitness. We orogastrically inoculated each of the libraries into mice and analyzed compositional changes in the populations over time in vivo compared to changes detected in the populations during library passage in vitro . The control library proliferated as a relatively stable community in vitro, but there was a reduction in the population diversity of this library in vivo and marked variation in the dominant strains recovered from individual animals, consistent with the existence of a non-selective bottleneck in vivo . We did not identify any OMP mutants exhibiting fitness defects exclusively in vivo without corresponding fitness defects in vitro . Conversely, a babA mutant exhibited a strong fitness advantage in vivo but not in vitro . These findings, when taken together with results of other studies, suggest that production of BabA may have differential effects on H. pylori fitness depending on the environmental conditions.

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Lactobacillus johnsonii La1 Attenuates Helicobacter pylori-Associated Gastritis and Reduces Levels of Proinflammatory Chemokines in C57BL/6 Mice

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.12.1378-1386.2005 ◽

2005 ◽

Vol 12 (12) ◽

pp. 1378-1386 ◽

Cited By ~ 56

Author(s):

Dionyssios N. Sgouras ◽

Effrosini G. Panayotopoulou ◽

Beatriz Martinez-Gonzalez ◽

Kalliopi Petraki ◽

Spyros Michopoulos ◽

...

Keyword(s):

Helicobacter Pylori ◽

Lamina Propria ◽

Serum Levels ◽

Favorable Effect ◽

Lactobacillus Johnsonii ◽

Ags Cells ◽

Inflammatory Infiltration ◽

H Pylori

ABSTRACT In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P = 0.038) and neutrophilic (P = 0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P = 0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P = 0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.

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A Novel 3-Deoxy-d-manno-Octulosonic Acid (Kdo) Hydrolase That Removes the Outer Kdo Sugar of Helicobacter pylori Lipopolysaccharide

Journal of Bacteriology ◽

10.1128/jb.187.10.3374-3383.2005 ◽

2005 ◽

Vol 187 (10) ◽

pp. 3374-3383 ◽

Cited By ~ 34

Author(s):

Christopher Stead ◽

An Tran ◽

Donald Ferguson ◽

Sara McGrath ◽

Robert Cotter ◽

...

Keyword(s):

Helicobacter Pylori ◽

Lipid A ◽

In Vitro Assay ◽

Spectrometric Analysis ◽

Vitro Assay ◽

The Core ◽

H Pylori

ABSTRACT The lipid A domain anchors lipopolysaccharide (LPS) to the outer membrane and is typically a disaccharide of glucosamine that is both acylated and phosphorylated. The core and O-antigen carbohydrate domains are linked to the lipid A moiety through the eight-carbon sugar 3-deoxy-d-manno-octulosonic acid known as Kdo. Helicobacter pylori LPS has been characterized as having a single Kdo residue attached to lipid A, predicting in vivo a monofunctional Kdo transferase (WaaA). However, using an in vitro assay system we demonstrate that H. pylori WaaA is a bifunctional enzyme transferring two Kdo sugars to the tetra-acylated lipid A precursor lipid IVA. In the present work we report the discovery of a Kdo hydrolase in membranes of H. pylori capable of removing the outer Kdo sugar from Kdo2-lipid A. Enzymatic removal of the Kdo group was dependent upon prior removal of the 1-phosphate group from the lipid A domain, and mass spectrometric analysis of the reaction product confirmed the enzymatic removal of a single Kdo residue by the Kdo-trimming enzyme. This is the first characterization of a Kdo hydrolase involved in the modification of gram-negative bacterial LPS.

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3-Pentylcatechol, a Non-Allergenic Urushiol Derivative, Displays Anti-Helicobacter pylori Activity In Vivo

Pharmaceuticals ◽

10.3390/ph13110384 ◽

2020 ◽

Vol 13 (11) ◽

pp. 384

Author(s):

Hang Yeon Jeong ◽

Tae Ho Lee ◽

Ju Gyeong Kim ◽

Sueun Lee ◽

Changjong Moon ◽

...

Keyword(s):

Helicobacter Pylori ◽

Triple Therapy ◽

Inflammatory Cells ◽

Control Group ◽

Vitro Assay ◽

Low Concentrations ◽

H Pylori ◽

Stomach Mucous Membrane

We previously reported that 3-pentylcatechol (PC), a synthetic non-allergenic urushiol derivative, inhibited the growth of Helicobacter pylori in an in vitro assay using nutrient agar and broth. In this study, we aimed to investigate the in vivo antimicrobial activity of PC against H. pylori growing in the stomach mucous membrane. Four-week-old male C57BL/6 mice (n = 4) were orally inoculated with H. pylori Sydney Strain-1 (SS-1) for 8 weeks. Thereafter, the mice received PC (1, 5, and 15 mg/kg) and triple therapy (omeprazole, 0.7 mg/kg; metronidazole, 16.7 mg/kg; clarithromycin, 16.7 mg/kg, reference groups) once daily for 10 days. Infiltration of inflammatory cells in gastric tissue was greater in the H. pylori-infected group compared with the control group and lower in both the triple therapy- and PC-treated groups. In addition, upregulation of cytokine mRNA was reversed after infection, upon administration of triple therapy and PC. Interestingly, PC was more effective than triple therapy at all doses, even at 1/15th the dose of triple therapy. In addition, PC demonstrated synergism with triple therapy, even at low concentrations. The results suggest that PC may be more effective against H. pylori than established antibiotics.

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