curcumin and Helicobacter-Infections

Helicobacter pylori is a significant human pathogen of the stomach's epithelial lining. This type of carcinogen is associated with gastric cancer, indigestion, peptic ulcers, and upper digestive diseases. Therefore, successful treatment and eradication of this bacterium are required to reduce the prevalence of these diseases, especially in high-risk individuals. Moreover, some concerns exist regarding the extensive use of elimination therapy, such as anti-microbial resistance and rising H. pylori-associated diseases. Since there is still no effective vaccine, finding alternative therapies would appear to be a worthwhile pursuit. In this regard, curcumin exhibits anti-inflammatory, anti-carcinogenic, anti-oxidant properties and is widely used as a natural product-derived medicine or nutraceutical. Furthermore, curcumin has been reported to have anti-bacterial activity. Therefore, curcumin might be an effective herbal-based medicine for preventing, managing, or treating H. pylori infection. This review discusses the anti-inflammatory, anti-cancer, and anti-bacterial properties of curcumin as it pertains to gastric cancer and H. pylori-associated diseases.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Curcumin; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms

Curcumin, a yellow pigment and principal polyphenolic Curcuminoid obtained from the turmeric rhizome Curcuma longa, is commonly used as a food-coloring agent. Studies suggest that curcumin has a wide range of beneficial properties e.g., anti-inflammatory, anti-oxidant, anti-cancer, anti-proliferative, anti-fungal and anti-microbial. These pleiotropic activities prompted several research groups to elucidate the role of curcumin in Helicobacter pylori (H. pylori) infection. This is the first review with this heading where we discussed regarding the role of curcumin as an anti-H. pylori agent along with its potential in other gastrointestinal diseases. Based on several in vitro, early cell culture, animal research and few pre-clinical trials, curcumin projected as a potential therapeutic candidate against H. pylori mediated gastric pathogenesis. This review sheds light on the anti-H. pylori effects of curcumin in different models with meticulous emphasis on its anti-oxidant, anti-inflammatory and anti-carcinogenic effects as well as some critical signaling and effecter molecules. Remarkably, non-toxic molecule curcumin fulfills the characteristics for an ideal chemopreventive agent against H. pylori mediated gastric carcinogenesis but the foremost challenge is to obtain the optimum therapeutic levels of curcumin, due to its low solubility and poor bioavailability. Further, we have discussed about the possibilities for improving its efficacy and bioavailability. Lastly, we concluded with the anticipation that in near future curcumin may be used to develop a therapeutic drug against H. pylori mediated gastric ailments through improved formulation or delivery systems, facilitating its enhanced absorption and cellular uptake.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antioxidants; Curcumin; Helicobacter Infections; Helicobacter pylori; Humans; Stomach Neoplasms; Treatment Outcome

Helicobacter pylori (H. pylori) is a Gram negative pathogen that selectively colonizes the human gastric epithelium. Over 50% of the world population is infected with H. pylori reaching up to 90% of infected individuals in developing countries. Nonetheless the increased impact upon public health care, its reservoir and the transmission pathway of the species has not been clearly established yet. Molecular studies allowed the detection of H. pylori in various aquatic environments, even forming biofilm in tap water distribution systems in several countries, suggesting a role of water as a possible reservoir of the pathogen. The persistence of human infection with H. pylori and the resistance of clinical isolates to commonly used antibiotics in eradication therapy have been related to the genetic variability of the species and its ability to develop biofilm, demonstrated both in vivo and in vitro experiments. Thus, during the last years, experimental work with this pathogen has been focused in the search for biofilm inhibitors and biofilm destabilizing agents. However, only two anti- H. pylori biofilm disrupting agents have been successfully used: Curcumin - a natural dye - and N-acetyl cysteine - a mucolytic agent used in respiratory diseases. The main goal of this review was to discuss the evidences available in the literature supporting the ability of H. pylori to form biofilm upon various surfaces in aquatic environments, both in vivo and in vitro. The results published and our own observations suggest that the ability of H. pylori to form biofilm may be important for surviving under stress conditions or in the spread of the infection among humans, mainly through natural water sources and water distribution systems.

Topics: Acetylcysteine; Anti-Bacterial Agents; Biofilms; Curcumin; Environment; Environmental Microbiology; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Water Microbiology

BackgroundFunctional dyspepsia is the main cause of upper abdominal discomfort affecting 5-10% of the world population. Despite various therapeutic approaches, up to 50% of patients with functional dyspepsia seek alternative treatments. In the present study we evaluated the effect of curcumin supplementation along with famotidine therapy on severity of functional dyspepsia. A total of 75 patients with functional dyspepsia according to Rome III criteria were allocated into intervention (N = 39) or control (N = 36) groups. The intervention group was treated with a combination of 500 mg curcumin and 40 mg famotidine daily for 1 month. The control group received placebo and 40 mg famotidine. Severity of dyspepsia symptoms was determined using the Hong Kong questionnaire at baseline, after the 1 month treatment and after a 1 month follow-up. The presence of H. pylori antigens in the stool samples was also investigated in all subjects. No significant difference was observed between intervention and control groups in biochemical indices, severity of dyspepsia and rate of H. pylori infection. A significant decrease was observed in severity of dyspepsia (p < 0.001) and rate of H. pylori infection (p = 0.004) immediately after the treatment and follow-up in the curcumin intervention group. This study indicated that curcumin therapy could be a favorable supplementation in the symptom management of functional dyspepsia. Moreover, curcumin could help efficient eradication of H. pylori in these patients.

Topics: Anti-Bacterial Agents; Curcumin; Double-Blind Method; Drug Therapy, Combination; Dyspepsia; Helicobacter Infections; Helicobacter pylori; Humans

Helicobacter pylori infection of the lining of the stomach induces an array of inflammatory cytokine production leading to gastritis and peptic ulcer disease. The aim of this study was to investigate the effect of curcumin on the production of interleukin (IL)-8, IL-1beta, tumor necrosis factor (TNF)-alpha and cyclooxygenase (COX)-2 in gastric mucosa from H. pylori-infected gastritis patients. Patients were randomly assigned to receive either OAM (Omeprazole, Amoxicillin and Metronidazole) treatment or a course of curcumin. Gastric biopsies were collected before and after treatment and were examined for the level of inflammatory cytokines mRNA by semi-quantitative reverse transcription polymerase chain reaction. The eradication rate of H. pylori in patients that received OAM treatment was significantly higher than the patients that received curcumin (78.9% versus 5.9%). The levels of IL-8 mRNA expression in the OAM group significantly decreased after treatment, but no changes of other cytokines were found. This emphasizes an important role of IL-8 in H. pylori infection. The decreases of cytokine production were not found in the curcumin group. We concluded that curcumin alone may have limited anti-bactericidal effect on H. pylori, and on the production of inflammatory cytokines. Nevertheless, other studies have reported that patients treated with curcumin had relieved symptoms. Further investigation should be carried out as the use of curcumin in combination with therapeutic regimens may be beneficial as an alternative treatment.

Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Bacterial Load; Curcumin; Drug Therapy, Combination; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Metronidazole; Middle Aged; Omeprazole

Curcumin is the principal element of turmeric powder extracted from the root of Curcuma longa. Studies on curcumin have demonstrated some anti-Helicobacter pylori activity as well as immunomodulating properties. N-acetylcysteine and lactoferrin with their respective mucolytic and antibacterial activities might also be effective in H. pylori eradication therapy.. To determine if a 7-day non-antibiotic therapy comprised of curcumin, lactoferrin, N-acetylcysteine, and pantoprazole was effective for eradication of H. pylori infection and reduction of gastric inflammation, assessed by serum pepsinogens and relief of symptoms.. Twenty-five consecutive H. pylori-positive patients (12 males, mean age 50 +/- 12 years, range 31-76) with functional dyspepsia were enrolled. Patients were administered for 7 days curcumin 30 mg b.i.d., bovine lactoferrin 100 mg b.i.d., N-acetylcysteine 600 mg b.i.d., and pantoprazole 20 mg b.i.d. H. pylori status and upper gastrointestinal symptoms were assessed by (13)C-urea breath test and a scale of upper gastrointestinal symptoms intensity (absent, mild, moderate, and severe), as well as a blood test for serum pepsinogens (sPGI, sPGII), gastrin-17 (G-17), and anti-H. pylori IgG (IgG-Hp) at baseline (T0) and after 2 months (T1).. Three of 25 patients (12%) were cured of H. pylori infection. A significant decrease in the overall severity of symptoms (T0: 6, interquartile range [IQR]: 4.5-8; T1: 2, IQR: 2-3; p < or = .001), and sPGII (T0: 16 microg/L, IQR: 13-22; T1: 10 microg/L, IQR: 8-16; p < or = .001) and sPGI (T0: 82 microg/L, IQR: 67-97; T1: 74 microg/L, IQR: 62-94; p = .02) levels were observed after 2 months of the treatment. IgG and G-17 values did not significantly decrease after 2 months.. This novel therapy was not effective for H. pylori eradication. However, despite the bacterium persistence, significant improvement of dyspeptic symptoms and reduction of serologic signs of gastric inflammation were observed after 2 months at the end of the 7-day treatment schedule.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Acetylcysteine; Adult; Aged; Curcumin; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Lactoferrin; Male; Middle Aged; Pantoprazole; Treatment Failure

Helicobacter pylori (H. pylori) is the main cause of gastric diseases. However, the traditional antibiotic treatment of H. pylori is limited due to increased antibiotic resistance, low efficacy, and low drug concentration in the stomach. This study developed a Nano-emulsion system with ability to carry Curcumin and Clarithromycin to protect them against stomach acidity and increase their efficacy against H. pylori. We used oil in water emulsion system to prepare a novel Curcumin Clarithromycin Nano-Emulsion (Cur-CLR-NE). The nano-emulsion was validated by dynamic light scattering (DLS) technique, zeta potential; transmission electron microscopy (mean particle size 48 nm), UV-visible scanning and Fourier transform infrared spectroscopy (FT-IR). The in vitro assay of Cur-CLR-NE against H. pylori was evaluated by minimum inhibitory concentration (12.5 to 6.26 µg/mL), minimum bactericidal concentration (MBC) and anti-biofilm that showed a higher inhibitory effect of Cur-CLR-NE in compere with, free curcumin and clarithromycin against H. pylori. The in vivo results indicated that Cur-CLR-NE showed higher H. pylori clearance effect than free clarithromycin or curcumin under the same administration frequency and the same dose regimen. Histological analysis clearly showed that curcumin is highly effective in repairing damaged tissue. In addition, a potent synergistic effect was obvious between clarithromycin and curcumin in nano-emulsion system. The inflammation, superficial damage, the symptoms of gastritis including erosion in the mouse gastric mucosa, necrosis of the gastric epithelium gastric glands and interstitial oedema of tunica muscularis were observed in the positive control infected mice and absent from treated mice with Cur-CLR-NE.

Topics: Animals; Anti-Bacterial Agents; Clarithromycin; Curcumin; Helicobacter Infections; Helicobacter pylori; Mice; Microbial Sensitivity Tests; Spectroscopy, Fourier Transform Infrared

Inhibition or disruption of biofilms has been recognized as an important means to eradicate Helicobacter pylori (H. pylori) infection. However, a fast and efficient drug screening method against H. pylori biofilms has not yet been established. Therefore, AlpB, an important outer membrane protein in H. pylori biofilm formation, was selected as a biological recognition element to screen anti-biofilm drugs in this study. A novel AlpB/colloidal gold (CG)/nanoporous gold (NPG)/Nafion-reduced graphene oxide (rGO)/glassy carbon electrode (GCE) biosensor was constructed based on the heterologous expression of AlpB. The prepared AlpB-based biosensor not only successfully identified six anti-biofilm drugs, but also evaluated the sensitivity and action intensity of different anti-biofilm drugs binding to AlpB by interaction kinetics analysis. The sensitivity order of AlpB to the six anti-biofilm drugs was: allicin > erythromycin > SCC > curcumin > rifampicin > NAC and the action intensity of the six anti-biofilm drugs on AlpB was: rifampicin > NAC > allicin > erythromycin > SCC > curcumin. In addition, molecular docking results showed that the six anti-biofilm drugs might exert their anti-biofilm effects by spontaneously binding to the conserved region of AlpB protein. This study provided a rapid screening platform and a unified data processing method for potential anti-biofilm drug development.

Topics: Bacterial Outer Membrane Proteins; Biofilms; Biosensing Techniques; Curcumin; Drug Evaluation, Preclinical; Erythromycin; Gold Colloid; Helicobacter Infections; Helicobacter pylori; Humans; Membrane Proteins; Molecular Docking Simulation; Nanopores; Rifampin

Curcumin is a hydrophobic polyphenol derived from turmeric with potent anti-oxidant, anti-microbial, anti-inflammatory and anti-carcinogenic effects. Curcumin is degraded into various derivatives under in vitro and in vivo conditions, and it appears that its degradation may be responsible for the pharmacological effects of curcumin. The primary risk factor for the cause of gastric cancer is

Topics: Anticarcinogenic Agents; Antineoplastic Agents; Antioxidants; Bacterial Proteins; Curcumin; Diacetyl; Helicobacter Infections; Helicobacter pylori; Humans; Molecular Docking Simulation; Oxidative Stress; Polyphenols; Vacuoles; Virulence Factors

Curcumin is a potential natural remedy for preventing

Topics: Animals; Antigens, Bacterial; Bacterial Proteins; Curcumin; Epithelial Cells; Escherichia coli; Helicobacter Infections; Helicobacter pylori; Mice; Phosphorylation

Topics: Anti-Bacterial Agents; Bacterial Proteins; Curcumin; Female; Helicobacter Infections; Helicobacter pylori; Humans; Light; Microbial Viability; Virulence; Virulence Factors

The anti-inflammatory and antimicrobial properties of curcumin suggest its use as an anti-

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Cells, Cultured; Curcumin; Down-Regulation; Female; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Interleukin-17; Male; Middle Aged; Up-Regulation; Young Adult

Antiulcer potency and inhibitory effects on Helicobacter pylori of structurally defined low molecular weight modified pectin from turmeric (MTrPP) has been previously demonstrated by us. Given that ulcer is a disorder characterized by inflammatory responses leading to initiation, aggravation and perpetuation of disease conditions, the present study aims to understand the possible anti-inflammatory mechanisms through which MTrPP delivered antiulcer effects. Rats triggered with early phase gastric inflammation (LPS) followed by ulcer induction (swim-stress) were pretreated with MTrPP (150 mg/kg b.w.) for 14 days. Inflammation and ulcer-specific markers were screened to assess the protective effects. MTrPP offered up to 91% protection by limiting the production of pro-inflammatory factors (TNF-α, IL-8, NF-κB) and by the tight differential regulation of cyclooxygenase (COX-1, 2), mitogen-activated-protein-kinase (p-p38, p-ERK-1/2) and matrix metalloproteinase (pro-MMP-9). MTrPP showed modulatory effects through inhibition of galectin-3, oxidative stress, H

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Curcuma; Helicobacter Infections; Helicobacter pylori; Interleukin-10; Male; Pectins; Peptic Ulcer; Rats; Rats, Wistar

Helicobacter pylori (H. pylori) infection triggers a sequence of gastric alterations starting with an inflammation of the gastric mucosa that, in some cases, evolves to gastric cancer. Efficient vaccination has not been achieved, thus it is essential to find alternative therapies, particularly in the nutritional field. The current study evaluated whether curcumin could attenuate inflammation of the gastric mucosa due to H. pylori infection. Twenty-eight C57BL/6 mice, were inoculated with the H. pylori SS1 strain; ten non-infected mice were used as controls. H. pylori infection in live mice was followed-up using a modified 13C-Urea Breath Test (13C-UBT) and quantitative real-time polymerase chain reaction (PCR). Histologically confirmed, gastritis was observed in 42% of infected non-treated mice at both 6 and 18 weeks post-infection. These mice showed an up-regulation of the expression of inflammatory cytokines and chemokines, as well as of toll-like receptors (TLRs) and MyD88, at both time points. Treatment with curcumin decreased the expression of all these mediators. No inflammation was observed by histology in this group. Curcumin treatment exerted a significant anti-inflammatory effect in H. pylori-infected mucosa, pointing to the promising role of a nutritional approach in the prevention of H. pylori induced deleterious inflammation while the eradication or prevention of colonization by effective vaccine is not available.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Disease Models, Animal; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Male; Mice; Mice, Inbred C57BL; Myeloid Differentiation Factor 88; Real-Time Polymerase Chain Reaction; Toll-Like Receptors; Up-Regulation

The oncoprotein cytotoxic associated gene A (CagA) of Helicobacter pylori plays a pivotal role in the development of gastric cancer, so it has been an important target for anti-H. pylori drugs. Conventional drugs are currently being implemented against H. pylori. The inhibitory role of plant metabolites like curcumin against H. pylori is still a major scientific challenge. Curcumin may represent a novel promising drug against H. pylori infection without producing side effects. In the present study, a comparative analysis between curcumin and conventional drugs (clarithromycin, amoxicillin, pantoprazole, and metronidazole) was carried out using databases to investigate the potential of curcumin against H. pylori targeting the CagA oncoprotein. Curcumin was filtered using Lipinski's rule of five and the druglikeness property for evaluation of pharmacological properties. Subsequently, molecular docking was employed to determine the binding affinities of curcumin and conventional drugs to the CagA oncoprotein. According to the results obtained from FireDock, the binding energy of curcumin was higher than those of amoxicillin, pantoprazole, and metronidazole, except for clarithromycin, which had the highest binding energy. Accordingly, curcumin may become a promising lead compound against CagA+ H. pylori infection.

Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Amoxicillin; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Proteins; Binding Sites; Clarithromycin; Computer-Aided Design; Curcumin; Drug Design; Helicobacter Infections; Helicobacter pylori; Metronidazole; Molecular Docking Simulation; Pantoprazole; Pattern Recognition, Automated; Protein Binding; Protein Conformation; Proton Pump Inhibitors; Structure-Activity Relationship

Current therapy-regimens against Helicobacter pylori (Hp) infections have considerable failure rates and adverse side effects that urge the quest for an effective alternative therapy. We have shown that curcumin is capable of eradicating Hp-infection in mice. Here we examine the mechanism by which curcumin protects Hp infection in cultured cells and mice. Since, MMP-3 and -9 are inflammatory molecules associated to the pathogenesis of Hp-infection, we investigated the role of curcumin on inflammatory MMPs as well as proinflammatory molecules. Curcumin dose dependently suppressed MMP-3 and -9 expression in Hp infected human gastric epithelial (AGS) cells. Consistently, Hp-eradication by curcumin-therapy involved significant downregulation of MMP-3 and -9 activities and expression in both cytotoxic associated gene (cag)(+ve) and cag(-ve) Hp-infected mouse gastric tissues. Moreover, we demonstrate that the conventional triple therapy (TT) alleviated MMP-3 and -9 activities less efficiently than curcumin and curcumin's action on MMPs was linked to decreased pro-inflammatory molecules and activator protein-1 activation in Hp-infected gastric tissues. Although both curcumin and TT were associated with MMP-3 and -9 downregulation during Hp-eradication, but unlike TT, curcumin enhanced peroxisome proliferator-activated receptor-γ and inhibitor of kappa B-α. These data indicate that curcumin-mediated healing of Hp-infection involves regulation of MMP-3 and -9 activities.

Topics: Animals; Cells, Cultured; Curcumin; Down-Regulation; Enzyme Inhibitors; Helicobacter Infections; Humans; Inflammation; Inflammation Mediators; Matrix Metalloproteinase 3; Matrix Metalloproteinase 9; Mice; Stomach

To investigate whether curcumin could attenuate nuclear factor (NF)-kappaB p65 expression and macromolecular leakage in the gastric mucosa of Helicobacter pylori (H. pylori)-infected rats.. Twenty-five male Sprague-Dawley rats were equally divided into five groups: control rats (Control), control rats supplemented with 600 mg/kg curcumin, H. pylori-infected rats (Hp), H. pylori-infected rats supplemented with 200 mg/kg curcumin (Hp + curI), and H. pylori-infected rats supplemented with 600 mg/kg curcumin (Hp + curII). In H. pylori-infected groups, rats were inoculated with H. pylori suspension twice a day at an interval of 4 h for 3 d. Two weeks later, 200 or 600 mg/kg curcumin was given once daily to curcumin-supplemented groups for 7 d. On the day of the experiment, macromolecular leakage in gastric mucosa was examined by intravital fluorescence microscopy. The stomach tissue was removed to examine NF-kappaB p65 expression in gastric epithelial cells by immunohistochemistry.. The expression of NF-kappaB p65 in gastric epithelial cells and the macromolecular leakage from gastric mucosal microcirculation significantly increased in the Hp group compared with the Control group. The percentages of NF-kappaB p65 immunoreactive cells in Control and Hp groups were 10.72% +/- 2.10% vs 16.02% +/- 2.98%, P = 0.004, respectively. The percentages of macromolecular leakage in Control and Hp groups were 10.69% +/- 1.43% vs 15.41% +/- 2.83%, P = 0.001, respectively. Curcumin supplementation in Hp + curI and Hp + curII groups significantly decreased NF-kappaB p65 immunoreactive cells and macromolecular leakage compared with results in the Hp group. The percentages of NF-kappaB p65 immunoreactive cells in Hp + curI and Hp + curII groups were 11.79% +/- 2.13% (P = 0.017) and 11.42% +/- 1.68% (P = 0.010), respectively. The percentages of macromolecular leakage in Hp + curI and Hp + curII groups were 12.32% +/- 2.13% (P = 0.025) and 12.14% +/- 1.86% (P = 0.018), respectively.. H. pylori-induced gastric inflammation in rats is associated with increased NF-kappaB activation and macromolecular leakage which can be reduced by curcumin supplementation.

Topics: Animals; Curcumin; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Male; Rats; Rats, Sprague-Dawley; Transcription Factor RelA

Treatment failure is a major cause of concern for the Helicobacter pylori-related gastroduodenal diseases like gastritis, peptic ulcer, and gastric cancer. Curcumin, diferuloylmethane from turmeric, has recently been shown to arrest H. pylori growth. The antibacterial activity of curcumin against 65 clinical isolates of H. pylori in vitro and during protection against H. pylori infection in vivo was examined. The MIC of curcumin ranges from 5 microg/ml to 50 microg/ml, showing its effectiveness in inhibiting H. pylori growth in vitro irrespective of the genetic makeup of the strains. The nucleotide sequences of the aroE genes, encoding shikimate dehydrogenase, against which curcumin seems to act as a noncompetitive inhibitor, from H. pylori strains presenting differential curcumin MICs showed that curcumin-mediated growth inhibition of Indian H. pylori strains may not be always dependent on the shikimate pathway. The antimicrobial effect of curcumin in H. pylori-infected C57BL/6 mice and its efficacy in reducing the gastric damage due to infection were examined histologically. Curcumin showed immense therapeutic potential against H. pylori infection as it was highly effective in eradication of H. pylori from infected mice as well as in restoration of H. pylori-induced gastric damage. This study provides novel insights into the therapeutic effect of curcumin against H. pylori infection, suggesting its potential as an alternative therapy, and opens the way for further studies on identification of novel antimicrobial targets of curcumin.

Topics: Animals; Anti-Bacterial Agents; Base Sequence; Curcumin; Helicobacter Infections; Helicobacter pylori; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Molecular Sequence Data; Stomach

Anomalous expression of activation-induced cytidine deaminase (AID) in Helicobacter pylori-infected gastric epithelial cells has been postulated as one of the key mechanisms in the development of gastric cancer. AID is overexpressed in the cells through nuclear factor (NF)-kappaB activation by H. pylori and hence, inhibition of NF-kappaB pathway can downregulate the expression of AID. Curcumin, a spice-derived polyphenol, is known for its anti-inflammatory activity via NF-kappaB inhibition. Therefore, it was hypothesized that curcumin might suppress AID overexpression via NF-kappaB inhibitory activity in H. pylori-infected gastric epithelial cells.. MKN-28 or MKN-45 cells and H. pylori strain 193C isolated from gastric cancer patient were used for co-culture experiments. Cells were pretreated with or without nonbactericidal concentrations of curcumin. Apoptosis was determined by DNA fragmentation assay. Enzyme-linked immunosorbent assay was performed to evaluate the anti-adhesion activity of curcumin. Real-time polymerase chain reaction was employed to evaluate the expression of AID mRNA. Immunoblot assay was performed for the analysis of AID, NF-kappaB, inhibitors of NF-kappaB (IkappaB), and IkappaB kinase (IKK) complex regulation with or without curcumin.. The adhesion of H. pylori to gastric epithelial cells was not inhibited by curcumin pretreatment at nonbactericidal concentrations (< or =10 micromol/L). Pretreatment with nonbactericidal concentration of curcumin downregulated the expression of AID induced by H. pylori. Similarly, NF-kappaB activation inhibitor (SN-50) and proteasome inhibitor (MG-132) also downregulated the mRNA expression of AID. Moreover, curcumin (< or =10 micromol/L) has suppressed H. pylori-induced NF-kappaB activation via inhibition of IKK activation and IkappaB degradation.. Nonbactericidal concentrations of curcumin downregulated H. pylori-induced AID expression in gastric epithelial cells, probably via the inhibition of NF-kappaB pathway. Hence, curcumin can be considered as a potential chemopreventive candidate against H. pylori-related gastric carcinogenesis.

Topics: Cell Line, Tumor; Curcumin; Cytidine Deaminase; Down-Regulation; Enzyme Activation; Epithelial Cells; Gastric Mucosa; Gene Expression Regulation, Enzymologic; Helicobacter Infections; Helicobacter pylori; Humans

Infection of epithelial cells by the microbial pathogen Helicobacter pylori leads to activation of the transcription factor nuclear factor kappaB (NF-kappaB), the induction of pro-inflammatory cytokine/chemokine genes, and the motogenic response (cell scattering). Here we report that H. pylori-induced NF-kappaB activation and the subsequent release of interleukin 8 (IL-8) are inhibited by curcumin (diferuloylmethane), a yellow pigment in turmeric (Curcuma longa L.). Our results demonstrate that curcumin inhibits IkappaBalpha degradation, the activity of IkappaB kinases alpha and beta (IKKalpha and beta), and NF-kappaB DNA-binding. The mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2) and p38, which are also activated by H. pylori infection, were not inhibited by curcumin. Further, the H. pylori-induced motogenic response was blocked by curcumin. We conclude that curcumin, due to inhibition of NF-kappaB activation and cell scattering, should be considered as a potential therapeutic agent effective against pathogenic processes initiated by H. pylori infection.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Movement; Curcumin; Dose-Response Relationship, Drug; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; NF-kappa B

Methanol extracts of the rhizomes of Sanguinaria canadensis, and the roots and rhizomes of Hydrastis canadensis, two plants used traditionally for the treatment of gastrointestinal ailments, were screened for in vitro antibacterial activity against 15 strains of Helicobacter pylori. The rhizome extracts, as well as a methanol extract of S. canadensis suspension-cell cultures inhibited the growth of H. pylori in vitro, with a MIC50 range of 12.5-50.0 microg/ml. Three isoquinoline alkaloids were identified in the active fraction. Sanguinarine and chelerythrine, two benzophenanthridine alkaloids, inhibited the growth of the bacterium, with an MIC50 of 50.0 and 100.0 microg/ml, respectively. Protopine, a protopine alkaloid, also inhibited the growth of the bacterium, with a MIC50 of 100 microg/ml. The crude methanol extract of H. canadensis rhizomes was very active, with an MIC50 of 12.5 microg/ml. Two isoquinoline alkaloids, berberine and beta-hydrastine, were identified as the active constituents, and having an MIC50 of 12.5 and 100.0 microg/ml, respectively.

Topics: Alkaloids; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Helicobacter Infections; Helicobacter pylori; Humans; Hydrastis; Isoquinolines; Microbial Sensitivity Tests; Phytotherapy; Plant Extracts; Plant Roots; Sanguinaria