Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases.

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.

Empiric Versus Clarithromycin Resistance-Guided Therapy for Helicobacter pylori Based on Polymerase Chain Reaction Results in Patients With Gastric Neoplasms or Gastric Mucosa-Associated Lymphoid Tissue Lymphoma: A Randomized Controlled Trial.

INTRODUCTION: We investigated to compare the effect of empirical therapy vs clarithromycin resistance-guided tailored therapy (tailored therapy) for eradication of Helicobacter pylori. METHODS: In this prospective, single center, open-label randomized controlled trial, we enrolled 72 patients with H. pylori infection from January 2019 through June 2019 in Korea. The patients were randomly assigned to both groups received empirical (n = 36) or tailored therapy (n = 36). Empirical therapy was defined as triple therapy with esomeprazole, amoxicillin, and clarithromycin for 10 days irrespective of clarithromycin resistance. Tailored therapy was triple or quadruple therapy with esomeprazole, metronidazole, tetracycline, and bismuth for 10 days based on genotype markers of resistance determined by gastric biopsy. Resistance-associated mutations in 23S rRNA were confirmed by multiplex polymerase chain reaction. Eradication status was assessed by C-urea breath test, and the primary outcome was eradication rates. RESULTS: H. pylori was eradicated in 27 patients (75.0%), given empirical therapy and 32 patients (88.9%) treated with tailored therapy (P = 0.136) in intention-to-treat analysis. In per protocol analysis, the eradication rate was 97.0% and 81.8% in tailoredvs empirical groups (P = 0.046). Although clarithromycin-resistant H. pylori was eradicated in 3/9 (33.3%) with empirical therapy, it was treated in 11/12 (91.7%) with tailored therapy (P = 0.009). There was no difference in compliance between 2 groups. The rate of adverse events of the tailored group was higher than that of the empirical group (P = 0.036) because quadruple therapy had more side effects than those of triple therapy (P = 0.001). DISCUSSION: Tailored therapy based on polymerase chain reaction is a good alternative to increase eradication rates in a region of high prevalence of clarithromycin resistance (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A342).

BabA and LPS inhibitors against Helicobacter pylori: pectins and pectin-like rhamnogalacturonans as adhesion blockers.

The first step in the development of Helicobacter pylori pathogenicity is receptor-mediated adhesion to gastric epithelium. Adhesins of H. pylori not only enable colonisation of the epithelium, with BabA interacting with Lewisb, but also interaction of lipopolysaccharide (LPS) with galectin-3 contributes to attachment of H. pylori to the host cells. Anti-adhesive compounds against H. pylori have been described, but specific analytical assays for pinpointing the interaction with BabA are limited. LPS-galectin-3 inhibitors have not been described until now. A sandwich ELISA with recombinant BabA547-6K was developed to investigate the interaction of BabA with Lewisb-HSA. Isothermal titration calorimetry gave thermodynamic information on the interaction between BabA, Lewisb-HSA and anti-adhesive compounds. A highly esterified rhamnogalacturonan from Abelmoschus esculentus inhibited the adhesion of H. pylori to adherent gastric adenocarcinoma (AGS) cells (IC50 550 µg/mL) and interacted with BabA (IC50 17 µg/mL). Pectins with similar rhamnogalacturonan structure showed weak anti-adhesive activity. Highly branched rhamnogalacturonans with low uronic acid content and high degree of esterification are potent BabA inhibitors. BabA represents a promising target for the development of anti-adhesive drugs against H. pylori. The rhamnogalacturonan influenced also the binding affinity of H. pylori to recombinant galectin-3 in a concentration-dependent manner with an IC50 of 222 µg/mL. Similar effects were obtained with pectin from apple fruits, while pectins from other sources were inactive.

Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl Alcohol Extract Inhibits AGS Cell Helicobacter pyloriCagA+VacA+ Promoted Invasiveness by Down-Regulating Caudal Type Homeobox Transcription Factor and Claudin-2 Expression.

OBJECTIVE: To investigate the effects and possible mechanisms of action of Curcuma wenyujin Y. H. Chen et C. Ling n-Butyl alcohol extract (CWNAE) on repression of human gastric cancer (GC) AGS cell invasion induced by co-culturing with Helicobacter pylori (HP). METHODS: AGS cells were cultured with HP of positive or negative cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) expression (CagA+/- or VacA+/-) and divided into 5 group. Group A was cultured without HP as a control, Group B with HPCagA+VacA+, Group C with HPCagA-VacA-, Group D with HPCagA+VacA+ and CWNAE, and Group E with HPCagA-VacA- and CWNAE. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and tumor invasion assays, examinations of morphology and ultramicroscopic structures, quantitative real-time polymerase chain reaction and Western blots were performed to measure the effects and uncover the mechanisms behind these effects of HPCagA+VacA+ and CWNAE on the epithelial-mesenchymal transition (EMT) of AGS cells. RESULTS: The 10% inhibitory concentration of CWNAE against AGS cells after a 48 h incubation was 19.73±1.30 µg/mL. More AGS cells were elongated after co-culturing with HPCagA+VacA+ than after culturing with HPCagA-VacA-. In tumor invasion assays, HPCagA+VacA+ significantly enhanced the invasiveness of AGS cells compared to the other experimental groups (all P value <0.05), and this effect was inhibited by CWNAE. Treatment with CWNAE normalized tight junctions and reduced the number of pseudopodia of AGS cells co-cultured with HPCagA+VacA+. HPCagA+VacA+ up-regulated zincfinger ebox binding homeobox 1 (ZEB1) in AGS cells after co-culturing for 24 h. Expression of caudal type homeobox transcription factor (CDX-2) and claudin-2 was significantly increased by HPCagA+VacA+ (P<0.05), but not by HPCagA-VacA-. CONCLUSION: HPCagA+VacA+ promoted the invasiveness of AGS cells through up-regulation of ZEB1 transcription and claudin-2 and CDX-2 expression. CWNAE inhibited these effects of HPCagA+VacA+ on AGS cells by down-regulating ZEB1 transcription, and CDX-2 and claudin-2 expression.

Artemisinin and its derivatives prevent Helicobacter pylori-induced gastric carcinogenesis via inhibition of NF-κB signaling.

BACKGROUND: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated. PURPOSE: We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA. METHODS: The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action. RESULTS: ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation. CONCLUSION: ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.

Serum Concentrations of 15 Elements Among Helicobacter Pylori-Infected Residents from Lujiang County with High Gastric Cancer Risk in Eastern China.

Helicobacter pylori (H. pylori) infection can interfere with the absorption of most elements, and the variations of some element levels are related to the incidence of gastric cancer. However, there have been conflicting results concerning the influence of H. pylori infection on serum element levels. The present study aimed to compare the serum element concentrations of H. pylori-infected local residents with uninfected residents from Lujiang County with high gastric cancer risk in Eastern China. We used data and serum samples from the H. pylori screening-survey program which was a cross-sectional study. We took 155 samples randomly from the screening survey, identified 74 H. pylori-positive residents and 81 H. pylori-negative residents by a serological test. The serum concentrations of 15 elements (calcium, magnesium, iron, zinc, selenium, copper, molybdenum, chromium, cobalt, nickel, lead, cadmium, mercury, arsenic, and aluminum) were determined using inductively coupled plasma mass spectrometry. Serum cobalt was found at higher levels in the H. pylori-infected residents than the H. pylori-uninfected residents (0.246 vs 0.205 µg/L, P = 0.022), but no statistically significant differences in the serum levels of other elements were found. This is the first study to report the serum concentrations of 15 elements and their relationships with the infection status of H. pylori among local residents from Lujiang County with high gastric cancer risk. Although the International Agency for Research on Cancer has classified cobalt and other soluble cobalt salts as possibly carcinogenic to human beings, our results may provide a clue to the relationships between cobalt, H. pylori, and gastric cancer.

Management of gastric mucosa-associated lymphoid tissue lymphoma in patients with extra copies of the MALT1 gene.

AIM: To identify the clinical features of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with extra copies of MALT1. METHODS: This is a multi-centered, retrospective study. We reviewed 146 patients with MALT lymphoma in the stomach who underwent fluorescence in situ hybridization analysis for t(11;18) translocation. Patients were subdivided into patients without t(11;18) translocation or extra copies of MALT1 (Group A, n = 88), patients with t(11;18) translocation (Group B, n = 27), and patients with extra copies of MALT1 (Group C, n = 31). The clinical background, treatment, and outcomes of each group were investigated. RESULTS: Groups A and C showed slight female predominance, whereas Group B showed slight male predominance. Mean ages and clinical stages at lymphoma diagnosis were not different between groups. Complete response was obtained in 61 patients in Group A (69.3%), 22 in Group B (81.5%), and 21 in Group C (67.7%). Helicobacter pylori (H. pylori) eradication alone resulted in complete remission in 44 patients in Group A and 13 in Group C. In Group B, 14 patients underwent radiotherapy alone, which resulted in lymphoma disappearance. Although the difference was not statistically significant, event-free survival in Group C tended to be inferior to that in Group A (P = 0.10). CONCLUSION: Patients with t(11;18) translocation should be treated differently from others. Patients with extra copies of MALT1 could be initially treated with H. pylori eradication, similar to patients without t(11;18) translocation or extra copies of MALT1.

Can Diet Modulate Helicobacter pylori-associated Gastric Pathogenesis? An Evidence-Based Analysis.

Helicobacter pylori is involved in the pathogenesis of gastritis, peptic ulcer, and gastric cancer. The infection is prevalent in more than half of the world's population. Although the infection may lead to detrimental consequences, still the majority of the infected individuals only develop mild gastritis. Several factors are behind this paradoxical outcome including virulence of the infecting H. pylori strains, genetic background of the host, and factors related to lifestyle such as dietary habits. Among these, lifestyle including dietary factors was not in the limelight, until recently, as one of the important factors that could modulate H. pylori-linked gastric diseases. This review is directed to gather and elucidate the role of dietary components in augmenting or attenuating pathological processes initiated by H. pylori. Available evidence strongly supports the notion that the diet may play a critical role in defining the final outcome of H. pylori infection particularly if certain dietary components are taken on a regular basis for a long time. Despite a recent surge in research related to the role of dietary ingredients, further studies involving large-scale clinical trials are required to gain a better understanding of the precise role played by the dietary ingredients in H. pylori-associated pathogenesis.

INHIBITORY ACTIVITY OF MANGIFERIN ON HELICOBACTER PYLORI-INDUCED INFLAMMATION IN HUMAN GASTRIC CARCINOMA AGS CELLS.

BACKGROUND: Gastric cancer is a serious health issue caused by H. pylori and claims more lives in developing and undeveloped countries. Hence, the need for a natural drug with several pharmacological activities with no adverse effect are highly recommended. The target of this study was to verify the anti-H. pyloric efficacy of mangiferin (MF) on H. pylori-infected AGS cells. MATERIALS AND METHODS: AGS cells were co-cultured with H. pylori and incubated with increased concentration of MF (10, 20, 50 and 100 µg/mL) or amoxicillin (AMX) and DMSO (control) group to assess its anti-H. pyloric effect by checking inhibitory zone, bacterial drug sensitivity test (MIC and MBC), adhesion and invasive property and various inflammatory markers. RESULTS: Co-culturing of H. pylori-infected AGS cells with MF (100 µg) considerably increased (p<0.05) the inhibitory zone as well as substantially lowered (p<0.05) in the levels of MBC and MIC with decreased adhesion and invasive property in a dose-dependent manner and thus endorsing its anti H. pyloric activity and are almost equivalent to antibiotic AMX. Meanwhile, inflammatory markers such as NF-κΒ subunit p65, interleukins-1ß, IL-8, and TNF-α were also markedly suppressed (p<0.01) on treatment with MF. In addition, the protein expression of inflammatory enzymes like COX-2 and iNOS were notably downregulated (p<0.05) in AGS cells incubated with MF. CONCLUSION: We, concluded that MF treatment with H. pylori-infected AGS cells significantly suppressed the adhesion and invasion process as well as deactivated NF-p65 thereby blocking inflammatory response and thus lower the incidence of gastric carcinoma.

Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Suppressed Helicobacter pylori-associated gastric tumorigenesis in Fat-1 transgenic mice producing endogenous ω-3 polyunsaturated fatty acids.

Dietary approaches to preventing Helicobacter pylori (H. pylori)-associated gastric carcinogenesis are widely accepted because surrounding break-up mechanisms are mandatory for cancer prevention, however, eradication alone has been proven to be insufficient. Among these dietary interventions, omega-3-polyunsaturated-fatty acids (ω-3 PUFAs) are often the first candidate selected. However, there was no trial of fatty acids in preventing H. pylori-associated carcinogenesis and inconclusive results have been reported, likely based on inconsistent dietary administration. In this study, we developed an H. pylori initiated-, high salt diet promoted-gastric tumorigenesis model and conducted a comparison between wild-type (WT) and Fat-1-transgenic (TG)-mice. Gross and pathological lesions in mouse stomachs were evaluated at 16, 24, 32, and 45 weeks after H. pylori infection, and the underlying molecular changes to explain the cancer preventive effects were investigated. Significant changes in: i) ameliorated gastric inflammations at 16 weeks of H. pylori infection, ii) decreased angiogenic growth factors at 24 weeks, iii) attenuated atrophic gastritis and tumorigenesis at 32 weeks, and iv) decreased gastric cancer at 45 weeks were all noted in Fat-1-TG-mice compared to WT-mice. While an increase in the expression of Cyclooxygenase (COX)-2, and reduced expression of the tumor suppressive 15-PGDH were observed in WT-mice throughout the experimental periods, the expression of Hydroxyprostaglandin dehydrogenase (15-PGDH) was preserved in Fat-1-TG-mice. Using a comparative protein array, attenuated expressions of proteins implicated in proliferation and inflammation were observed in Fat-1-TG-mice compared to WT-mice. Conclusively, long-term administration of ω-3 PUFAs can suppress H. pylori-induced gastric tumorigenesis through a dampening of inflammation and reduced proliferation in accordance with afforded rejuvenation.

Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases.

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.

The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance.

Extranodal marginal zone (MZ) B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) arise from lymphoid populations that are induced by chronic inflammation in extranodal sites. The best evidence of an etiopathogenetic link is provided by the association between Helicobacter pylori-positive gastritis and gastric MALT lymphoma. Indeed, successful eradication of this microorganism with antibiotics can be followed by gastric MALT lymphoma regression in most cases. Other microbial agents have been implicated in the pathogenesis of MZ lymphoma arising at different sites. Apart from gastric MALT lymphoma, antibiotic therapies have been adequately tested only in ocular adnexal MALT lymphomas where upfront doxycycline may be a reasonable and effective initial treatment of patients with Chlamydophila psittaci-positive lymphoma before considering more aggressive strategies. In all other instances, antibiotic treatment of nongastric lymphomas remains investigational. Indeed, there is no clear consensus for the treatment of patients with gastric MALT lymphoma requiring further treatment beyond H pylori eradication or with extensive disease. Both radiotherapy and systemic treatments with chemotherapy and anti-CD20 antibodies are efficacious and thus the experience of individual centers and each patient's preferences in terms of adverse effects are important parameters in the decision process.

EVIDENCE BASE OF LACTOBACILLUS REUTERI EFFICACY IN THE TREATMENT OF DISEASES ASSOCIATED WITH HELICOBACTER PYLORI.

Helicobocterpylori (HP) - the human infection that persists for a long time in the stomach and can cause chronic gastritis, gastric and duodenal ulcer, MALT-lymphoma, gastric adenocarcinoma. There is a well-adapted niche-specific microbial community in the stomach represented by Lactobocillus, Streptococcus ahd other bacteria. Use of probiotics is considered to be an alternative or supplement to eradication therapy Among the Lactobacillus the most promising is Loctobocillus reutert who are able to have the anti-HP activity L. reureri produces powerful antimicrobial compounds such as reuterin, reuteritsin 6, reutetsiklin and metabolites that inhibit the growth of I-/P (volatile fatty acids, lactic acid, hydrogen peroxide, etc.). These compounds could reduce the adhesion of HP to gastric epithelial cells, inhibit growth HP, which leads to a significant reduction in the degree of contamination of HP and the severity of gastric mucosal inflammation. The data on the effectiveness of L. re uteri as monotherapy in patients with HP without absolute indications for eradication, and as an additional component, which increase the effectiveness of eradication are presented.

Acetylated Rhamnogalacturonans from Immature Fruits of Abelmoschus esculentus Inhibit the Adhesion of Helicobacter pylori to Human Gastric Cells by Interaction with Outer Membrane Proteins.

Polysaccharide containing extracts from immature fruits of okra (Abelmoschus esculentus) are known to exhibit antiadhesive effects against bacterial adhesion of Helicobacter pylori (H. pylori) to stomach tissue. The present study investigates structural and functional features of polymers responsible for this inhibition of bacterial attachment to host cells. Ammonium sulfate precipitation of an aqueous extract yielded two fractions at 60% and 90% saturation with significant antiadhesive effects against H. pylori, strain J99, (FE60% 68% ± 15%; FE90% 75% ± 11% inhibition rates) after preincubation of the bacteria at 1 mg/mL. Sequential extraction of okra fruits yielded hot buffer soluble solids (HBSS) with dose dependent antiadhesive effects against strain J99 and three clinical isolates. Preincubation of H. pylori with HBSS (1 mg/mL) led to reduced binding to 3'-sialyl lactose, sialylated Le(a) and Le(x). A reduction of bacterial binding to ligands complementary to BabA and SabA was observed when bacteria were pretreated with FE90%. Structural analysis of the antiadhesive polysaccharides (molecular weight, monomer composition, linkage analysis, stereochemistry, and acetylation) indicated the presence of acetylated rhamnogalacturonan-I polymers, decorated with short galactose side chains. Deacetylation of HBSS and FE90% resulted in loss of the antiadhesive activity, indicating esterification being a prerequisite for antiadhesive activity.

Treatment Strategy for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Recent trends and current knowledge on the diagnosis and treatment strategy for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are reviewed. Helicobacter pylori infection plays the causative role in the pathogenesis, and H pylori eradication is the first-line treatment of this disease, which leads to complete remission in 60% to 90% of cases. A Japanese multicenter study confirmed that the long-term outcome of gastric MALT lymphoma after H pylori eradication is excellent. Treatment strategies for patients not responding to H pylori eradication including "watch and wait" strategy, radiotherapy, chemotherapy, rituximab immunotherapy, and combination of these should be tailored in consideration of the disease extent in each patient.

Review: Pharmacological ins and outs of medicinal plants against Helicobacter pylori: A review.

Since Helicobacter pylori was discovered in 1980, it has been considered as a major cause in the pathogenesis of gastric ulcer, mucosa-associated lymphoid tissue (MALT) lymphomas, and gastric cancer. Eventually antibiotics were designed to eradicate this bacterium, which not only prevent peptic ulcer recurrence but also decrease the chances of developing gastric cancer. Propitious consequences of these antibiotic regimens and better hygienic conditions, particularly in developed countries, resulted in significant decline in the prevalence of H. pylori infection. However, persistent high H. pylori infection in developing countries, decreased patience compliance and emerging antibiotic resistance forced researchers to quest for novel candidates. Herbal medicines have always served as a leading source in drug discovery. Since time immemorial, herbs have been used to treat various disorders covering from minor illnesses as pain to life threatening conditions like cancer. Ample amount of studies from different parts of the world have shown promising activities of medicinal herbs not only against H. pylori but also associated disorders while employing in vitro, in vivo and clinical studies. In this review, these multiple pharmacological effects of medicinal plants and their chemical constituents will be discussed in relation to H. pylori not only to scientifically evaluate the beneficial effects of these medicinal plants but to also critically analyze their plausible role as chemo preventive agents against H. pylori-associated disorders.

In vivo treatment of Helicobacter pylori infection with liposomal linolenic acid reduces colonization and ameliorates inflammation.

Helicobacter pylori infection is marked by a vast prevalence and strong association with various gastric diseases, including gastritis, peptic ulcers, and gastric cancer. Because of the rapid emergence of H. pylori strains resistant to existing antibiotics, current treatment regimens show a rapid decline of their eradication rates. Clearly, novel antibacterial strategies against H. pylori are urgently needed. Here, we investigated the in vivo therapeutic potential of liposomal linolenic acid (LipoLLA) for the treatment of H. pylori infection. The LipoLLA formulation with a size of ∼ 100 nm was prone to fusion with bacterial membrane, thereby directly releasing a high dose of linolenic acids into the bacterial membrane. LipoLLA penetrated the mucus layer of mouse stomach, and a significant portion of the administered LipoLLA was retained in the stomach lining up to 24 h after the oral administration. In vivo tests further confirmed that LipoLLA was able to kill H. pylori and reduce bacterial load in the mouse stomach. LipoLLA treatment was also shown to reduce the levels of proinflammatory cytokines including interleukin 1ß, interleukin 6, and tumor necrosis factor alpha, which were otherwise elevated because of the H. pylori infection. Finally, a toxicity test demonstrated excellent biocompatibility of LipoLLA to normal mouse stomach. Collectively, results from this study indicate that LipoLLA is a promising, effective, and safe therapeutic agent for the treatment of H. pylori infection.

Genetic polymorphisms and tissue expression of interleukin-22 associated with risk and therapeutic response of gastric mucosa-associated lymphoid tissue lymphoma.

Chronic Helicobacter pylori-stimulated immune reactions determine the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. We aimed to explore the genetic predisposition to this lymphoma and its clinical implication. A total of 68 patients and 140 unrelated controls were genotyped for 84 single-nucleotide polymorphisms in genes encoding cytokines, chemokines and related receptors that play important roles in T cell-mediated gastrointestinal immunity. Five genotypes in IL-22, namely CC at rs1179246, CC at rs2227485, AA at rs4913428, AA at rs1026788 and TT at rs7314777, were associated with disease susceptibility. The former four genotypes resided in the same linkage disequilibrium block (r(2)=0.99) that conferred an approximately threefold higher risk. In vitro experiments demonstrated that co-culturing peripheral mononuclear cells or CD4(+) T cells with H. pylori stimulated the secretion of interleukin-22 (IL-22), and that IL-22 induced the expression of antimicrobial proteins, RegIIIα and lipocalin-2, in gastric epithelial cells. Furthermore, patients with gastric tissue expressing IL-22 were more likely to respond to H. pylori eradication (14/22 vs 4/19, P<0.006). We conclude that susceptibility of gastric MALT lymphoma is influenced by genetic polymorphisms in IL-22, the product of which is involved in mucosal immunity against H. pylori and associated with tumor response to H. pylori eradication.