Research - Helicobactor pylori infection
Fucoidans Disrupt Adherence of Helicobacter pylori to AGS Cells In Vitro
Eng-Guan Chua, Phebe Verbrugghe, Timothy T. Perkins, and Chin-Yen Tay
Fucoidans are complex sulphated polysaccharides derived from abundant and edible marine algae.Helicobacter pylori is a stomach pathogen that persists in the hostile milieu of the human stomach unless treated with antibiotics. This study aims to provide preliminary data to determine, in vitro, if fucoidans can inhibit the growth of H. pylori and its ability to adhere to gastric epithelial cells (AGS). We analysed the activity of three different fucoidan preparations (Fucus A, Fucus B, and Undaria extracts). Bacterial growth was not arrested or inhibited by the fucoidan preparations supplemented into culture media. All fucoidans, when supplemented into tissue culture media at 1000 µg mL−1, were toxic to AGS cells and reduced the viable cell count significantly. Fucoidan preparations at 100 µg mL−1 were shown to significantly reduce the number of adherent H. pylori. These in vitro findings provide the basis for further studies on the clinical use of sulphated polysaccharides as complementary therapeutic agents.
Source : Evidence Based Complementary and Alternative Medicine
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The association between objective tongue color and endoscopic findings: results from the Kyushu and Okinawa population study (KOPS)
Mosaburo Kainuma12*, Norihiro Furusyo2, Yoshihisa Urita3, Masaharu Nagata1, Takeshi Ihara2, Takeshi Oji5, Toshiya Nakaguchi4, Takao Namiki5 and Jun Hayashi6
Background The relation between tongue color and gastroesophageal disease is unclear. This study was done to investigate the associations between tongue color (TC), endoscopic findings, Helicobacter.pylori infection status, and serological atrophic gastritis (SAG).
Methods The participants were 896 residents of Ishigaki Island, Okinawa, aged 28–86 years. The tongue was photographed, esophagogastroduodenoscopy was done, and serum antibody to H.pylori was measured. SAG was defined as a serum Pepsinogen (PG)Ilevel ≤70 ng/ml and a PGI/IIratio ≤3.0. TC was measured by the device-independent international commission on Illumination 1976 L*a*b* color space standards at four points: (1) edge, (2) posterior, (3) middle, and (4) apex. We also calculated the ratio of the tongue edge to the three other measured points to examine the association between the coating of the tongue and the endoscopic and laboratory findings.
Results Participants were excluded who had two or more endoscopic findings (n = 315) or who had SAG without seropositivity to H.pylori (n = 33). The remaining 548 participants were divided into three groups: SAG and seropositive to H.pylori (n = 67), seropositive to H.pylori alone (n = 56), and without SAG and seronegative for H.pylori (n = 425). We divided 425 residents into a single endoscopic finding positive group (n = 207) and a negative group, which served as a control (n = 218). The most frequent single endoscopic finding was esophageal hernia (n = 110), followed by erosive esophagitis (n = 35) and erosive gastritis (EG) (n = 45). EH was significantly associated with TC (2b*/1b*) (P < 0.05). EG was significantly associated with TC (3a*, 3b*) (P < 0.05). Seropositivity to H.pylori was significantly associated with TC (3 L*, 3 L*/1 L*) (P < 0.05, <0.01), and seropositivity to both H.pylori and SAG was significantly associated with TC (3 L*/1 L*) (P < 0.05). Multivariate analysis extracted TC (3a*, 3b*) as an independent factor associated with a differential diagnosis of EG (Odds ratio (OR) 2.66 P = 0.008, OR 2.17 P = 0.045).
Conclusions The tongue body color of the middle area reflects acute change of gastric mucosa, such as erosive gastritis. Tongue diagnosis would be a useful, non-invasive screening tool for EG.
Source : BMC Complementary and Alternative Medicine
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In vitro effect of bergamot (Citrus bergamia) juice againstcagA-positive and-negative clinical isolates of Helicobacter pylori
Angela Filocamo1, Carlo Bisignano2, Nadia Ferlazzo1, Santa Cirmi1, Giuseppina Mandalari1* and Michele Navarra1*
Helicobacter pylori infection has been associated with chronic gastritis, peptic ulcer and gastric carcinoma as over half of the world's population is colonized with this gram-negative bacterium. Due to the increasing antibiotic resistance, its eradication rates fails in a great portion of patients. A number of studies showed that molecules largely distributed in commonly consumed fruits and vegetables may have antimicrobial activity. The aim of the present study was to investigate the effect of bergamot juice (BJ) against Helicobacter pylori in vitro. The potential therapeutic combination between BJ and the antibiotics amoxicillin (AMX), clarithromycin (CLA) and metronidazole (MTZ) has also been evaluated.
MethodsThe minimum inhibitory concentration (MIC) of BJ, AMX, CLA and MTZ against 2 ATCC and 32 clinical isolates of H. pylori was assayed according to CLSI. The checkerboard method was used to determine the efficacy of the association BJ with the three reference antibiotics.
Killing curves were performed on the two cagA-positive ATCC strains of H. pylori (ATCC 43504 and ATCC 49503), on the clinical isolate cagA-positive HP6 strain of H. pylori and on the clinical isolatecagA-negative HP61 strain of H. pylori.
ResultsBJ (2.5 %, v/v) inhibited the growth of 50 % of the H. pylori clinical isolates, whereas 5 % (v/v) inhibited 90 %. AMX was the most effective antibiotic against the reference strains and the clinical isolates, followed by CLA and MTZ. In the combination assays, synergism was observed between BJ and AMX and between BJ and MTZ against both the reference strains and the clinical isolates. Indifference was observed between BJ and CLA.
Conclusions BJ was effective in vitro against H. pylori and the genotype status of the clinical strains may have an impact on its susceptibility. The synergistic combination of BJ and antibiotics could be used to prevent or treat resistance.
Source : BMC Complementary and Alternative Medicine
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Dietary functional benefits of Bartlett and Starkrimson pears for potential management of hyperglycemia, hypertension and ulcer bacteria Helicobacter pylori while supporting beneficial probiotic bacterial response
Pear has potential for phenolic-linked management of type 2 diabetes associated hyperglycemia and hypertension.
Fermented pear juices also possess inhibitory activity of stomach ulcer relevant bacteriumHelicobacter pylori.
Pear cultivars have relevance to be included in dietary strategies for better management of early stage hyperglycemia.
This in vitro study provides conceptual foundation for animal and clinical studies involving pear to combat type 2 diabetes.
Phenolic-linked health benefits of Bartlett and Starkrimson pear cultivars were investigated for the potential relevance in managing type 2 diabetes and hypertension using in vitro enzyme models. Further effects of fermented (0, 24, 48, and 72-h with Lactobacillus helveticus) pear juice on inhibition of Helicobacter pyloriand proliferation of probiotic Bifidobacterium longum were also evaluated. High total phenolic content along with high 2,2 diphenyl-1-picrylhydrazyl-linked free radical scavenging antioxidant activities were observed in peel extracts of both cultivars. In vitro enzyme assays with peel and pulp extracts also indicated high inhibitory activity of α-glucosidase and α-amylase used as models for anti-hyperglycemia benefits. Only the aqueous pulp extract of Bartlett pear had angiotensin I-converting enzyme inhibitory activity used as model for anti-hypertension benefits. Fermented acidic pH samples of both cultivars showed H. pylori inhibition at 48 and 72 h, while fermented sample of Starkrimson even showed inhibition at 24 h. Both cultivar extracts did not inhibit growth of probiotic B. longum
Source : Food Research International
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A REVIEW ON THE ANTI-INFLAMMATORY ACTIVITY OF POMEGRANATE IN THE GASTRO-INTESTINAL TRACT
1Elisa Colombo, 1Enrico Sangiovanni, 1, 2Mario Dell'Agli*
1Department of Pharmacological and Biomolecular Sciences, and 2Research Centre for
Characterization and Safe Use of Natural Compounds-G. Galli, Università degli Studi di Milano, Via Balzaretti 9, Milano, Italy
PG is used in the traditional medicine of different Asian cultures for the treatment of a variety of ailments. The biological activity of pomegranate has been widely investigated, including in vitro, in vivo and clinical studies. The beneficial effects are mostly the cardiovascular protective role, neuroprotective activity, hypoglycemic effect and anticancer properties, in particular against prostate, colon and breast cancer; the anticancer effect are limited only to in vitro and animal studies. The gastrointestinal tract represents an important barrier between the human hosts and microbial populations. One potential consequence of host-microbial interactions is the development of mucosal inflammation, which can lead to gastritis and ulcer. Gastritis defined as inflammation of the gastric mucosa can be caused by endogenous and exogenous factors including acid, pepsin, stress, and noxious agents such as alcohol, non-steroidal anti-inflammatory drugs, Helicobacter pylori infection and smoking. Conversely, inflammatory bowel diseases, among which Crohn’s disease and ulcerative colitis, are the most common inflammatory-related diseases in the gut; inflammatory bowel diseases occur in response to genetic or environmental factors and are characterized by the uncontrolled response of the intestinal immune system against the normal enteric microflora, leading to abdominal pain and chronic diarrhoea.
Although the anti-inflammatory properties of pomegranate and its major components have been widely described in the literature and some papers have been published at this regard, surprisingly this effect has not been reviewed till now. The aim of the present review is to summarize the evidence for or against the efficacy of pomegranate for coping inflammatory conditions of the gastro-intestinal tract.
The review has been organized in three parts: 1) a first one is devoted to the modifications of pomegranate active compounds in the gastro-intestinal tract, with particular attention to the intestinal metabolites; 2) a second one considering the literature regarding the anti-inflammatory effect of pomegranate and individual compounds at gastric level; 3) a third part considering the antiinflammatory effect of pomegranate and individual compounds in the gut, taking into account also the main metabolites which are formed by microbial biotransformation after pomegranate consumption. In vivo studies performed on the whole fruit or juice, peel and flowers demonstrate high anti-ulcer effect in a variety of animal models. Ellagic acid was found to be the main responsible for this effect, although other individual ellagitannins, which have not yet been studied, could contribute to the biological activity of the mixture.Different preparations of pomegranate, including extracts from peels, flowers, seeds, and juice, show a significant anti-inflammatory activity in the gut. Oil derived from PG seeds and its major 3 component punicic acid, inhibits the expression of pro-inflammatory cytokines through the modulation of PPAR-γ and δ, whereas pomegranate peel extracts, and the pure compounds
punicalagins and ellagic acid, inhibit the expression and secretion of several inflammatory mediators. The inhibitory effect is ascribed to the inhibition of the NF-κB pathway and involves the MAPKs system as well. Between urolithins, urolithins A has been shown to possess a significant antiinflammatory activity both in vitro and in vivo, thus suggesting that this compound, and not its
precursor EA, could be the main responsible for the anti-inflammatory properties observed with PG extracts in the gut. Unfortunately, no clinical studies addressing the anti-inflammatory activity of PG at the gastro-intestinal level have been found, thus suggesting that future clinical studies on antiinflammatory activity at the gastrointestinal tract are necessary to clarify the beneficial effects of pomegranate for human health.
Few in vitro studies have been performed with PG peel extracts to evaluate anti H. pylori activity. These extracts are able to reduce significantly the growth of this pathogen, which is considered the aetiological agent mainly responsible for human gastritis.
In vivo studies performed on the whole fruit or juice, peel and flowers, demonstrate high anti-ulcer effect in a variety of animal models. EA was found to be the main responsible for this effect, although other individual ETs, which have not yet been studied, could contribute to the biological activity of the mixture. With the exception of EA, the effect of the pure compounds at the gastric
level was not investigated; this should be carefully considered for the future studies, since these molecules appear to be unmodified at the gastric level. Conversely, the positive effect of EA has been widely demonstrated, and the effect is corroborated by other studies performed on other plants: ethanolic extract from Ficus glomerata fruit (FGE) contained 0.36% w/w of EA and showed significant dose-dependent anti-ulcerogenic in different models of induced gastritis (pylorus ligation, ethanol and cold stress) ; moreover, the hydroalcoholic extract of Anogeissus latifolia (50% alcohol) containing 0.25% w/w of EA, has been shown to possess gastro-protective activity  due to the presence of EA. In addition, methanol stem bark extract of Lafoensia pacari containing 23.4% 19 of EA showed gastro-protective and ulcer healing effects in animal models strictly associated to the
presence of great amounts of EA in the extract , and an improvement of the gastric symptoms in patients with H. pylori gastritis was observed . The mechanism of action by which EA shows anti-ulcer activity is partially attributed to the inhibitory effect on the gastric H+, K+-ATPase, in addition to the anti-H. pylori activity .
Unfortunately, no clinical studies coping with the anti-inflammatory activity of PG at the gastric level have been found, thus suggesting that the effect of the extracts and individual compounds in this area need to be elucidated. In particular, it is necessary to draw clinical trials considering the effects of PG extracts in patients with H. pylori-induced gastritis, alone or in combination with antibiotics. Different preparations of PG, including extracts from peels, flowers, seeds, in addition to the juice, show a significant anti-inflammatory activity in the gut. From all the studies taken into consideration in the present review, some conclusions can be drawn. First of all, the pure compounds occurring in PG fruits seem to act through different pathways. Oil derived from PG seeds and its major component PuA, could inhibit the expression of pro-inflammatory cytokines (such as IL-6, IL-8, IL-23, IL-12 and TNF-α) through the modulation of PPAR-γ and δ. This is not true for PG peel extracts, as well as their components punicalagins and EA, since they do not show any effect on PPAR signalling; conversely, the main effect is due to the inhibition of the expression and secretion of several inflammatory mediators (i.e. IL-6, IL-8, MCP-1, iNOS, COX-2 and PGE2). The inhibitory effect is ascribed to the inhibition of the NF-κB pathway and involves the MAPKs system as well. This effect was confirmed both in vitro and in vivo for the extracts and the pure compound punicalagin, while contradictory results were found for EA, since it seems to be effective also in studies performed in vivo. This might be explained considering the metabolic fate of PG phenolic compounds. In fact, different studies demonstrate a strong interaction between gut microbiota and PG polyphenols (i.e EA) that are metabolized by intestinal microflora to urolithins. These metabolites themselves could modulate gut microbiota, enhancing the growth of beneficial strains in spite of pathogenic ones. Between urolithins, urolithins A has been shown to possess a significant antiinflammatory activity both in vitro and in vivo, thus suggesting that this compound, and not its precursor EA, could be the main responsible for the anti-inflammatory properties observed with PG extracts in the gut. However it has been also showed that the inflammatory status alters the composition of intestinal microbiota, changing its metabolic capacity and the bioavailability of phenolic compounds . This statement is corroborated by observation that, after consumption of PG extract, the phenolic profile of faeces obtained from healthy and DSS-fed rats is deeply changed: in normal conditions EA and punicalagin are completely metabolized to urolithins A, whereas in inflammatory conditions they can be found unmodified in the colon . This suggests that 20 biological effects of urolithins, and consequently PG, could be strictly related to the composition of individual microbiota and to the intestinal inflammatory status. For this reason, although the studies reported herein seem to recommend PG consumption to prevent or treat gastro-intestinal inflammation, future clinical studies on anti-inflammatory activity at the gastrointestinal tract are necessary to clarify the beneficial effects of PG for human health.
Source : Evidence Based Complementary and Alternative Medicine
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Antibacterial activity of Tabebuia impetiginosa Martius ex DC (Taheebo) against Helicobacter pylori
Byeoung-Soo Park a, Hyun-Kyung Lee a, Sung-Eun Lee b, Xiang-Lan Piao c, Gary R. Takeoka d, Rosalind Y. Wong d, Young-Joon Ahna, Jeong-Han Kima,∗
a School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea
b Department of Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, Honolulu HI 96822, USA
c College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea
d Western Regional Research Center, Agricultural Research Service, U.S. Department of Agriculture, Albany CA 94710, USA
The growth-inhibiting activity of Tabebuia impetiginosa Martius ex DC dried inner bark-derived constituents against Helicobacter pylori ATCC 43504 was examined using paper disc diffusion and minimum inhibitory concentration (MIC) bioassays. The activity of the isolated compounds was compared to that of the commercially available anti-Helicobacter pylori agents, amoxicillin, metronidazole, and tetracycline. The biologically active components of Tabebuia impetiginosa dried inner bark (taheebo) were characterized by spectroscopic analysis as 2-(hydroxymethyl)anthraquinone,anthraquinone-2-carboxylic acid, and 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone (lapachol). With the paper disc diffusion assay 2-(hydroxymethyl)anthraquinone exhibited strong activity against Helicobacter pylori ATCC 43504 at 0.01 mg/disc. Anthraquinone-2-carboxylic acid, lapachol and metronidazole were less effective, exhibiting moderate anti-Helicobacter pylori activity at 0.1 mg/disc. Amoxicillin and tetracycline were the most potent compounds tested, displaying very strong activity at 0.005 mg/disc. 2-(Hydroxymethyl)anthraquinone exhibited moderate activity at this dose. Tetracycline still had strong activity at 0.001 mg/disc while amoxicillin had little activity at this dose. In the MIC bioassay, 2-(hydroxymethyl)anthraquinone (2g/mL), anthraquinone-2-carboxylic acid (8 g/mL), and lapachol (4 g/mL) were more active than metronidazole (32 g/mL) but less effective than amoxicillin (0.063 g/mL) and tetracycline (0.5 g/mL). The anti-Helicobacter pylori activity of seven 1,4-naphthoquinone derivatives (structurally related to lapachol), 1,4-naphthoquinone, 5,8-dihydroxy-1,4-naphthoquinone (naphthazarin), 2-methyl-1,4-naphthoquinone (menadione), 2-hydroxy-1,4-naphthoquinone (lawsone), 5-hydroxy-2-methyl-1,4-naphthoquinone (plumbagin), 5-hydroxy-1,4-naphthoquinone (juglone), and 2,3-dichloro-1,4-naphthoquinone (dichlone) was also evaluated using the paper disc assay. Menadione and plumbagin were the most potent compounds tested with the later still exhibiting very strong activity at 0.001 mg/disc. Menadione, juglone and tetracycline had strong activity at this low dose while the latter two compounds and amoxicillin had very strong activity at 0.005 mg/disc. Lawsone was unusual in that it had very strong activity at 0.1 and 0.05 mg/disc but weak activity at doses of 0.01 mg/disc and lower. Naphthazalin, lapachol and dichlone had similar activities while metronidazole had the lowest activity of all compounds tested.
These results may be an indication of at least one of the pharmacological actions of taheebo. The Tabebuia impetiginosa dried inner barkderived materials, particularly 2-(hydroxymethyl)anthraquinone, merit further study as potential Helicobacter pylori eradicating agents or lead compounds.
Source : Journal of Ethnopharmacology
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