Article

High Molecular Weight Polysaccharides from Black Currant Seeds Inhibit Adhesion of Helicobacter pylori to Human Gastric Mucosa

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  • knoell Germany GmbH
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Abstract

Several crude and purified polysaccharides from black currant seeds (Ribes nigrum L.) have been isolated, analysed and examined on their effects against Helicobacter pylori in in situ adhesion studies on sections of human gastric mucosa. After pre-treatment of Helicobacter pylori with 0.01 to 0.1 % solutions of the isolated raw polysaccharide (RPS), the epithelial binding of the bacteria was considerably reduced in a concentration-dependent manner, as compared with a non-treated control suspension. Preincubation of the mucosal sections with 0.1 % solutions did not result in a reduced binding of non-treated bacteria. An anion-exchange fraction of RPS eluted with 0.1 M phosphate buffer exhibited a comparable, concentration-dependent reduction of adhesion, whereas the water-eluted fraction was ineffective at the respective concentrations. Both subfractions consisted of similar 1,3-linked galactans, decorated with side chains possessing 1,4-galacturonic acid, galactose and arabinose residues. Molecular weight profiling by GPC revealed that the antiadhesive activity of the buffer eluate correlated with high molecular weight components ranging from about 1000 Da to 340 kDa, whereas the ones of the inactive water eluate had molecular weights of about 100 and 25 kDa, respectively. None of the active fractions revealed inhibitory effects on bacterial growth in vitro. We conclude that acidic, high molecular weight galactans are responsible for the antiadhesive qualities of black currant seed extracts and that these polymers are able to block Helicobacter surface receptors, thus inhibiting their interaction with specific binding factors located on human gastric epithelia.

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... A raw polysaccharide (RSP) obtained by water extraction and ethanolic precipitation was characterized by Lengsfeld et al. fraction showed more consistent ability to inhibit in situ H. pylori adhesion to sections of human gastric mucosa from H. pylori-negative patients. This was attributed to the larger molecular weight and also to the negative charge due to the presence of galacturonic acid (120). The active acidic fraction of larger molecular weight (~ 1000 kDa) was characterized and recognized as an arabinogalactan protein (AGP) bearing ca. ...
... EPS1190 was a branched polysaccharide, free of protein and constituted mainly by glucose and galactose without presence uronic acid residues. As observed previously, the absence of negative charges deriving from uronic acid residues or sulfate groups is detrimental to the interaction with the bacteria (113,120,140,150). In support to this statement, Ascencio et al. ...
... Throughout this review, the state-of the art on the interactions of polysaccharides with H. pylori is reflected (summarized in Representation of sugar residues is according with symbol and color code nomenclature proposed in www.glycopedia.eu 1 structure proposed in (180) 2 structure proposed in (181) Weak bound to tissue sections, however acquire ability to colonize gastric mice mucosa after mouse-adaptation; not able to induce IL-8 production in Kato III (120,190,191) ATCC 43504 (or NCTC 11637 or CCUG 17874 ...
Article
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The standard eradication treatment of the hostile Helicobacter pylori (H. pylori) infection is facing increasing alarming antibiotic resistance worldwide and calls for alternative strategies to the use of antibiotics. One new perspective in this direction is cytoprotective compounds for targeted prevention of the adhesion of the bacteria to the stomach host cell and to inhibit the bacterial cell-cell communication via quorum sensing by specific inhibitors. Bacterial adhesion of H. pylori to the host cells is mainly mediated by carbohydrate-protein interactions. Therefore, the use of polyvalent carbohydrates, (e.g. plant-derived polysaccharide), as potential antiadhesive compounds, seems to be a promising tool to prevent the initial docking of the bacterium to the stomach cells. Polysaccharides are common constituents of daily food, either as starch or as dietary fiber and often also function as excipients for galenic drug-delivery formulations. In addition, polysaccharides with defined pharmacodynamics action against bacterial outer membrane proteins can have potential as therapeutic tools in the treatment of bacterial infections. Some polysaccharides are known to possess antibacterial properties against gram-positive bacteria, others to inhibit bacterial colonization by blocking specific carbohydrate-receptors involved in host-bacteria interaction. This mode of action is advocated as alternative antiadhesion therapy. Ongoing research is also seeking for polysaccharide-based nanoformulations with potential for local drug delivery at the stomach as novel H. pylori therapies. These approaches pose challenges concerned with the stability of the nanomaterials in the harsh conditions of the gastric environment and their capacity to adhere to the stomach mucosa. In a global scenario geographical diversity and social habits, namely lifestyle and dietary factors, influence the prevalence of the H. pylori-associated diseases and their severity. In this context, the exploration of the biological activity of plant-derived products or polysaccharides commonly present in foods is increasingly becoming more and more attractive. This review aims to present the current state-of-the-art on the antiadhesive capacity of different polysaccharide families, on polysaccharide-based nanosystems and the proof-of-concept evidence of their potential use as alternative medicines against H. pylori.
... To date, much attention has been paid to carbohydrates as anti-adhesive agents of potential medicinal value (Lengsfeld et al., 2004;Sharon, 2006;Wittschier et al., 2007aWittschier et al., ,b, 2009). Proanthocyanidins may represent another group of promising anti-adhesion compounds, though reasonable studies are hitherto confined to Vaccinium polyphenols for the prophylaxis of urinary tract infections and, to some extent, to Helicobacter pylori-associated gastritis (Schmidt et al., 2004;Nowack and Schmitt, 2008). ...
... However, specific interactions may well occur as evident from the current work and from studies on cranberries, with prodelphinidins and A-type proanthocyanidins as anti-adhesive compounds, respectively. Recalling the anti-Helicobacter activity (Burger et al., 2002;Beil and Kilian, 2007;Wittschier et al., 2007a,b), the mode of anti-adherence action has commonly been related to negatively charged compounds, i.e. acidic polysaccharides (Lengsfeld et al., 2004). Detection of sulphated prodelphinidins (Schötz and Nöldner, 2007) may thus provide an additional chemical rationale for the reported anti-adhesive action of EPs ® 7630, which needs to be explored by future research, taking into account coumarin sulphates and polysaccharides. ...
... na showed significant cytotoxic effects of more than 20 % which gives a realistic anti-adhesion result for those two Fomitopsis betulina extracts. In our opinion, two groups of substances could be responsible for the anti-adhesive activity: polysaccharides for the activity of the aqueous extract and triterpenes for the activity of the MeOH extract.Lengsfeld et al. (2004) demonstrated that the antiadhesive activity of blackcurrant (Ribes nigrum L.) seed against Helicobacter pylori was caused by polysaccharides141 . To the best of our knowledge, antiadhesive effects of triterpenes are till now not described.Further investigation of the single substances of this mushroom should be done to identify clearly ...
... Only the H 2 O extract of Fomitopsis betulina showed significant cytotoxic effects of more than 20 % which gives a realistic anti-adhesion result for those two Fomitopsis betulina extracts. In our opinion, two groups of substances could be responsible for the anti-adhesive activity: polysaccharides for the activity of the aqueous extract and triterpenes for the activity of the MeOH extract.Lengsfeld et al. (2004) demonstrated that the antiadhesive activity of blackcurrant (Ribes nigrum L.) seed against Helicobacter pylori was caused by polysaccharides141 . To the best of our knowledge, antiadhesive effects of triterpenes are till now not described.Further investigation of the single substances of this mushroom should be done to identify clearly the responsible compounds of the anti-adhesive effect. ...
Thesis
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Zeyad Alresly The aim of the present dissertation was to investigate the biological and chemical potential of two European mushroom species: Fomitopsis betulina and Calvatia gigantea. For this purpose, different extracts of both fungi were tested for: antimicrobial, antifungal, cytotoxic, in vitro wound healing, and anti-adhesive properties. Bioassay-guided fractionation led to the isolation of bioactive compounds, altogether 20 compounds were isolated and identified. The compounds were obtained from the ethyl acetate extracts, they included triterpenes, sterols and aromatic compounds. The separated substances from both fungi were proved for biological activities, some of them showed antimicrobial and cytotoxic activities.
... Arabinogalactan proteins have galactose and arabinose residues and additionally include xylose carbohydrate residues as well. 35,36 L-ascorbic acid (Fig. 3), also known as vitamin C, is an essential non-volatile organic acid and a potent antioxidant and free radical scavenger. Several studies have evaluated the ascorbic acid content in blackcurrants, which was found to vary between 70-280 mg per 100 g of fresh fruit. ...
... Acidic, high molecular weight galactans found in blackcurrant seed extracts were shown to have anti-adhesive effects against Helicobacter pylori in sections of the human gastric mucosa, thus carrying antidotal prospects for virtually all duodenal ulcers. 35 Although unknown, it has been postulated that the mechanism of action may involve blocking the interactions between the mucosal epithelial cells and the surface receptors of the organism. With regards to the microbial effects on the composition of the particular constituents of the blackcurrants, microbial enzymes were found to deconjugate glycosylated compounds, such as anthocyanins. ...
Article
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The blackcurrant (Ribes nigrum L., Grossulariceae), a small, perennial shrub native to central Europe and northern Asia, is cultivated throughout the world, including the United States. In addition to its anecdotal use in traditional herbal medicine, modern laboratories have demonstrated the potent anti-inflammatory, antioxidant and antimicrobial effects of blackcurrant constituents on a myriad of disease states. The properties of the blackcurrants are conferred from its biochemical constituents, some of which include anthocyans (specifically delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside), flavonols, phenolic acids and polyunsaturated fatty acids. A plethora of studies have been published with regards to its various therapeutic applications. This article attempts to summarize these studies, providing a general overview of the research in this field. Several studies focus on the therapeutic potential of blackcurrants with regards to hypertension and other cardiovascular-associated illnesses, neoplastic, neurodegenerative and ocular diseases, nephrolithiasis, and diabetic neuropathy. Safety concerns and future directions are also mentioned, suggesting the critical examination of the exact mechanism of action, specific radical-scavenging capabilities of the blackcurrants and the crucial need for well-designed clinical trials to ensure the successful use of blackcurrants in a clinical setting.
... Testing against adhesion of H. pylori Adhesion and antiadhesion tests were performed according to [9], [10]. In principle, FITC-labelled bacteria were preincubated with the test compounds (1 mg/mL). ...
... The FITC-labelled H. pylori is incubated with sections from human stomach, and epithelial adhesion is evaluated after removing non-adhering bacteria by extensive washing. Bacteria not treated with test compounds served as full adhering control, while sialyllactose and Abelmoschus esculentus extract [10] as adhesion blockers were used as positive control [9]. After preincubation (1 mg/ mL) of the bacteria with 8, a strong and reproducible anti-adhesive effect with nearly complete blockage was observed while 5 was not active (Fig. 5 and Fig. 1S in the Supporting Information, Table 2). ...
... Historically, the identification of anti-adhesive compounds against H. pylori has been based on the initial finding of antiadhesive properties of 3′-sialyllactose (Mysore et al. 1999); unfortunately, this compound failed to prevent bacterial colonisation of human stomach in a clinical pilot study (Parente et al. 2003), likely owing to rapid degradation of the compound under physiological conditions in the stomach. The search for additional anti-adhesive compounds has yielded peptides (Niehues et al. 2010), polyphenols Wittschier et al. 2007;Shmuely et al. 2004) and polysaccharides (Wittschier et al. 2009;Lengsfeld et al. 2004;Messing et al. 2014b;Menchicchi et al. 2015) that interact with different OMPs. In many of these reports, the antiadhesive activity is well documented, but it remains unclear which OMP is addressed by the test compounds. ...
... Voucher species (IPBP 463) are retained in the archive of the authors' institute. The extract was prepared according to Lengsfeld et al. (2004). Briefly, 200 g of immature fruits were homogenised with 500 mL water for 10 min at 4°C. ...
Article
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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.
... Zawartość składników prozdrowotnych w porzeczce czarnej w znacznym stopniu zależy od genotypu, chociaż wpływ na nią mają również warunki wzrostu [16]. Analiza składu chemicznego liści, pąków i nasion porzeczki czarnej potwierdziła, że podobnie jak owoce, także i te części rośliny zawierają cenne składniki i mogą być źródłem bioak-tywnych produktów naturalnych wykorzystywanych w codziennej diecie, produkcji nutraceutyków, żywności funkcjonalnej, kosmetyków [17,20,26,28]. Wiedza na temat składu i prozdrowotnych efektów wywieranych przez bioaktywne substancje zawarte w nasionach, liściach i pąkach nie jest tak powszechna jak znajomość właściwości owoców. ...
... Wyizolowano galaktany o masie cząsteczkowej od ok. 10 3 Da do 340·10 3 Da, które in vitro hamowały adhezję Helicobacter pylori do błony śluzowej żołądka człowieka. Te polimery blokują receptory obecne na powierzchni komórek Helicobacter i w ten sposób uniemożliwiają bakteriom interakcję z błonami komórkowymi nabłonka żołądka [17]. Preparat zawierający polisacharydy uzyskane w wyniku trawienia nasion wpływał na przebieg alergii wywołanej przez cedr, podczas której obserwowano podwyższony poziom immunoglobuliny biorącej udział w reakcjach alergicznych IgE. ...
Article
Blackcurrant is a plant cultivated for its tasty fruit eaten fresh and in a processed form. The blackcurrant fruit is a valuable diet component because of its high content of health-promoting compounds such as vitamin C, phenolic compounds, and minerals. Buds, leaves, and seeds of blackcurrant constitute a relatively unknown source of bioactive compounds with pro-health and medicinal properties. Traditional medicine utilizes buds, leaves and currant seeds to treat certain diseases. Contemporary scientific research confirms the beneficial effect of those underestimated parts of the blackcurrant plant. The main bioactive compounds contained in black currant buds are essential oils including hydrocarbons and terpenes. Bud oils are characterized by a strong antibacterial and antifungal activity. Another group of bioactive substances are phenolic compounds, mainly rutin, epicatechin, and kaempferol. Owing to those substances¸ the buds have antioxidant and anti-inflammatory properties. Oil made from seeds of black currant can be an excellent source of unsaturated fatty acids and tocopherols, especially α-tocopherol. It also contains sterols known for the anti-atherosclerotic and anticancer activity. Black currant seed extracts contain large amounts of beneficial biologically active substances such as phenolic compounds and polysaccharides, mainly galactans. Owing to their high content of various phenolic compounds and essential oils, leaf extracts have antioxidant properties. Black currant leaves have a unique fatty acid composition with the potential anti-cancer, anti-inflammatory and antimicrobial activity. The potassium to sodium ratio in the leaves is high and this explains the diuretic effect of their infusions. The paper presents some application examples of the buds, seeds, and leaves. The objective of the study was to systematise the knowledge of the pro-health applications of extracts from those raw materials. © 2018, Polskie Towarzystwo Technologow Zywnosci Wydawnictwo Naukowe PTTZ. All rights reserved.
... To date, much attention has been paid to carbohydrates as anti-adhesive agents of potential medicinal value (Lengsfeld et al., 2004;Sharon, 2006;Wittschier et al., 2007aWittschier et al., ,b, 2009). Proanthocyanidins may represent another group of promising anti-adhesion compounds, though reasonable studies are hitherto confined to Vaccinium polyphenols for the prophylaxis of urinary tract infections and, to some extent, to Helicobacter pylori-associated gastritis (Schmidt et al., 2004;Nowack and Schmitt, 2008). ...
... However, specific interactions may well occur as evident from the current work and from studies on cranberries, with prodelphinidins and A-type proanthocyanidins as anti-adhesive compounds, respectively. Recalling the anti-Helicobacter activity (Burger et al., 2002;Beil and Kilian, 2007;Wittschier et al., 2007a,b), the mode of anti-adherence action has commonly been related to negatively charged compounds, i.e. acidic polysaccharides (Lengsfeld et al., 2004). Detection of sulphated prodelphinidins (Schötz and Nöldner, 2007) may thus provide an additional chemical rationale for the reported anti-adhesive action of EPs ® 7630, which needs to be explored by future research, taking into account coumarin sulphates and polysaccharides. ...
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Journal of Ethnopharmacology j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / j e t h p h a r m Evaluation of an aqueous-ethanolic extract from Pelargonium sidoides (EPs ® 7630) for its activity against group A-streptococci adhesion to human HEp-2 epithelial cells a b s t r a c t Aim of the study: The root extract of Pelargonium sidoides DC (Geraniaceae), EPs ® 7630, is currently used to treat respiratory tract infections. The therapeutic benefits are largely related to the modulation of the non-specific immune system. The present study was designed to investigate the anti-adhesive activity of this herbal medicine with Streptococcus pyogenes as model microorganism and to identify the underlying biologically active principle. Materials and methods: Adherence of fluorescent-labelled group A-streptococci (GAS) to human epithe-lial (HEp-2) cells was assessed by flow cytometry. Anti-adhesive properties of the parent extract as well as a methanol-soluble (MSF) and a methanol-insoluble fraction (MIF) derived thereof were examined. Treatment with skin powder produced polyphenol-free samples which were included for compari-son. Anti-adherence studies were extended to a series of highly purified proanthocyanidins including homogenous epicatechin-and catechin-based polyflavans, a 'mixed' procyanidin sample, an A-type proanthocyanidin mixture as well as a prodelphinidin test substance. Results: After pre-treatment of GAS with EPs ® 7630 or its subfractions MIF and MSF at concentrations of 30 ␮g/ml, adhesion of the pathogen to HEp-2 cells was inhibited by ca. 45%, ca. 35% and ca. 30%, respectively. However, following preincubation of cells with the extract and the fractions no effect was observed. This finding indicates that the anti-adhesive effects are due to interactions with binding factors on the bacterial surface. Since polyphenol-free samples proved to be inactive, proanthocyanidins appear to represent the anti-adhesive principle. Comparative studies with chemically defined proanthocyanidins revealed that the prodelphinidin nature, i.e. the pyrogallol B-ring elements of constituent flavanyl units, represented an important structural feature of the anti-adhesive potential of this herbal medicine. Conclusions: The current data provide strong evidence for a potent anti-adhesion principle of the Pelargo-nium sidoides root extract related to specific proanthocyanidins. This finding suggests an interaction with bacterial binding sites in a specific rather than non-specific manner. However, the blocked adhesion molecules remain to be identified. The anti-adhesive mechanism may well contribute to the anti-infective activity of EPs ® 7630 at an early time point of a bacterial infection.
... A range of putative host receptors for H. pylori have been identified, including sialylated and fucosylated antigens and sulfated carbohydrates [8]. A potential target for new therapies is therefore carbohydrate-based bacterial anti-adhesives that can inhibit the recognition and attachment of H. pylori to gastric epithelial tissue, leading to a diminished incidence of infection and also prevent reinfection of the stomach after antibiotic eradication therapy [6,[9][10][11]. Carbohydrates are ideal for this purpose due to their low toxicity and lack of harmful side effects. In addition, since anti-adhesive agents do not act by killing or arresting the growth of the pathogens, the problem of bacterial resistance will be emerging at a markedly lower rate than what is the current challenge with antibiotics [12]. ...
... For confirmation of these results an in situ assay on murine buccal mucosa sections was performed based on a protocol of [40,46]. Therefor bacteria were pretreated with test samples (only medium for untreated control group, TLCK (5 mM) for positive control, RA1 (100 μg/mL) for 90 minutes. ...
Article
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Background: The aerial parts of Rumex acetosa L. have been used in traditional European medicine for inflammatory diseases of the mouth epithelial tissue. The following study aimed to investigate the influence of a proanthocyanidin-enriched extract from R. acetosa extract against the adhesion of Porphyromonas gingivalis (P. gingivalis), a pathogen strongly involved in chronic and aggressive periodontitis. A further goal was to define the bioactive lead structures responsible for a potential antiadhesive activity and to characterize the underlying molecular mechanisms of the antiadhesive effects. Methodology: An extract of R. acetosa (RA1) with a defined mixture of flavan-3-ols, oligomeric proanthocyanidins and flavonoids, was used. Its impact on P. gingivalis adhesion to KB cells was studied by flow cytometry, confocal laser scanning microscopy and in situ adhesion assay using murine buccal tissue. RA1 and its compounds 1 to 15 were further investigated for additional effects on gingipain activity, hemagglutination and gene expression by RT-PCR. Principal findings: RA1 (5 to 15 μg/mL) reduced P. gingivalis adhesion in a dose-dependent manner to about 90%. Galloylated proanthocyanidins were confirmed to be responsible for this antiadhesive effect with epicatechin-3-O-gallate-(4β,8)-epicatechin-3'-O-gallate (syn. procyanidin B2-di-gallate) being the lead compound. Ungalloylated flavan-3-ols and oligomeric proanthocyanidins were inactive. RA1 and the galloylated proanthocyanidins strongly interact with the bacterial virulence factor Arg-gingipain, while the corresponding Lys-gingipain was hardly influenced. RA1 inhibited also hemagglutination. In silico docking studies indicated that epicatechin-3-O-gallate-(4β,8)-epicatechin-3'-O-gallate interacts with the active side of Arg-gingipain and hemaglutinin from P. gingivalis; the galloylation of the molecule seems to be responsible for fixation of the ligand to the protein. In conclusion, the proanthocyanidin-enriched extract RA1 and its main active constituent procyanidin B2-di-gallate protect cells from P. gingivalis infection by inhibiting bacterial adhesion to the host cell. RA1 and procyanidin B2-di-gallate appear to be promising candidates for future cytoprotective preparations for oral mouth care products.
... Historically, the identification of antiadhesive compounds against H. pylori has been based on the initial finding of antiadhesive properties of 39-sialyllactose [4]; unfortunately, this compound failed to prevent bacterial colonizaton of human stomach in a preliminary clinical study [5], likely owing to degradation of the compound under physiological conditions in the stomach. The search for additional antiadhesive compounds has yielded peptides [6], polyphenols [7][8], N-phenylpropenoyl-Lamino acid amides [9], and polysaccharides [10][11] that interact with bacterial outer membrane proteins (OMPs). The clinical and economic development of such antiadhesives is still underrepresented, in many cases because it is economically difficult to obtain sufficient amounts of these natural products at reasonable prices. ...
Article
Background: Traditional Asian and African medicine use immature okra fruits (Abelmoschus esculentus) as mucilaginous food to combat gastritis. Its effectiveness is due to polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach tissue. The present study investigates the antiadhesive effect in mechanistic detail.
... Cranberry nondialyzable materials have been found to inhibit the sialic acid-specific adhesion of antibioticresistant and nonresistant H. pylori to human gastric mucosa, a critical step in gastric ulcer development, at concentrations that is likely to be achieved after the consumption of cranberry juice cocktail (Shmuely et al., 2004). Similarly high molecular weight polysaccharides from black currant seed extracts were reported to inhibit adhesion of H. pylori to human gastric mucosa (Lengsfeld et al., 2004). Nohyenk et al. (2006) have reported that phenolic extracts (1 mg/ml concentration) from cloudberry, bilberry, black current, raspberry and strawberry could inhibit the growth of H. pylori. ...
Article
Epidemiological reports as well as experimental studies have demonstrated the significant health benefits provided by regular berry consumption. Berries possess both prophylactic and therapeutic potential against several chronic illnesses, such as cardiovascular, neurodegenerative and neoplastic diseases. Berries owe their health benefits to phytoconstituents, such as polyphenolic anthocyanins, ellagic acid and a diverse array of phytochemicals bestowed with potent antioxidant and anti-inflammatory effects as well as the ability to engage a multitude of signaling pathways. This review highlights the principal chemical constituents present in berries and their primary molecular targets. The article presents and critically analyzes the chemopreventive and therapeutic potential of berry extracts, fractions and bioactive components on various cancers of the gastrointestinal tract (GIT), including esophageal, stomach, intestinal and colorectal cancers as well as cancers of the upper aerodigestive tract, such as oral cancer. The current status of clinical studies evaluating berry products in several aforementioned cancers is presented. Various emerging issues including dose-ranging and dosage forms, the role of synergy and the usage of combination therapy as well as other relevant areas essential for the development of berry phytoconstituents as mainstream chemopreventive and therapeutic agents against aerodigestive and GIT cancers are critically discussed.
... In the present study, both the aand b-glucosidase activities as well the b-galactosidase activity in the distal intestine were significantly elevated under the effect of dietary blackcurrant seed oil, whereas the obesogenic diet partly counteracted those effects. However, these results may also be a consequence of other components present in large quantities in blackcurrant seeds, like flavonoid glucosides and glucose and galactose polymers [25,26], whose traces could have appeared in the oil after the extraction process. ...
Article
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Purpose: It was hypothesised that blackcurrant seed oil beneficially modulates metabolic disorders related to obesity and its complications. The study also aimed to investigate the potentially adverse effects of an unbalanced diet on the distal intestine. Methods: Male Wistar rats were randomly assigned to four groups of eight animals each and were fed a basal or obesogenic (high in fat and low in fibre) diet that contained either rapeseed oil (Canola) or blackcurrant seed oil. A two-way analysis of variance was then applied to assess the effects of diet and oil and the interaction between them. Results: After 8 weeks, the obesogenic dietary regimen increased the body weight, altered the plasma lipid profile and increased the liver fat content and the plasma transaminase activities. In addition, the obesogenic diet decreased bacterial glycolytic activity and short-chain fatty acid formation in the distal intestine. Dietary blackcurrant seed oil improved the lipid metabolism by lowering liver fat accumulation and the plasma triglyceride concentration and atherogenicity as well by increasing the plasma HDL-cholesterol concentration. However, in rats fed an obesogenic diet containing blackcurrant seed oil, the plasma HDL-cholesterol concentration was comparable with both rapeseed oil-containing diets, and a significant elevation of the plasma transaminase activities was noted instead. Conclusions: The obesogenic dietary regimen causes a number of metabolic disorders, including alterations in the hindgut microbial metabolism. Dietary blackcurrant seed oil ameliorates the lipid metabolism; however, the beneficial effect is restricted when it is provided together with the obesogenic diet, and a risk of liver injury may occur.
... Antibacteria effect [42],[43] Hypoglycemic effect [44] Inhibitory activities of mucilages & gums [45] III. RESEARCH FRAMEWORK ...
Article
Diabetes is characterized by excessive blood sugar due to body's failure to produce insulin or the consequence of insulin resistance. Nowadays, human suffering not only on the disease itself but also includes diabetes-related complications. All these abnormality are significantly important because of their effects on the liver function. Therefore this paper will provides an overview of the research framework to investigate the differential expression analysis of liver tissue in streptozotocin-induced diabetic rat in response to Abelmoschus esculentus (AE) treatment. The hypoglycemic effects of water extract prepared from the fruit of AE will be studied in diabetic rats (streptozotocin induced). All animals will be randomly divided into three group; normal healthy group (N group), streptozotocin–induced diabetic group (STZ group) and AE-treated diabetic group (AE group). Oral application of AE at doses of 100, 150 and 200 mg/kg body weight will be given to AE-treated diabetic group by single and repeated oral administration. Rats liver from these three groups will then subjected to RNA extraction for gene expression analysis. The differential expression study will be carried out by using real time RT-PCR method. Four diabetes-specific genes of interest (carboxylesterase 2, stearoyl-Coenzyme A desaturase 1, insulin-like growth factor 1 and insulin-like growth factor binding protein 2 binding protein) are chosen and the expression level of these genes will be examined quantitatively. The abnormal expression of genes in STZ group will be rescued by the AE therapy. The expected findings from both in vivo and molecular studies may reveal the anti-diabetic properties of the AE and suggest that the plant extract may be useful for the management of the disease. This paper will provide the overview of the research framework and giving insight of the experimental procedure to be implemented.
... Ribes nigrum bud essential oils exhibited powerful antibacterial activity against pathogens as Acinetobacter baumanii, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, as proved by the very low minimum inhibitory concentration values observed when applied on their strains (Oprea et al., 2008). Lengsfeld et al. (2004) observed that galactans, with high molecular weight 1,3-linked with side chains possessing 1,4-galacturonic acid, along with galactose and arabinose residues were provide the antiadhesive qualities of seed extracts. These polymers blocked Helicobacter pylori surface receptors, hindering their interaction with specific binding elements on the gastric epithelia. ...
Article
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The blackcurrant is known as a crop plant in Europe from the 16th century. Its fruits, rich in carbohydrates, fatty acids, proteins and mineral substances, are used to prepare juice, syrup, jelly or marmalade. The fruits have a general tonic, vitaminizing and remineralizing effect, being recommended in cases of overwork, in anemic conditions, in cases of iron deficiency. The flowers are also used in perfumery. Leafs are used in the herbal medicine as diuretic, in heart diseases, rheumatism, or gout. The blackcurrant contains tannins, rutin, vitamin C, trepenic volatile oil. The fruits contain vitamin C, vitamins of B complex, organic acids (citric, malic), pectins, sugars, anthocyans, fatty oil, trepenes, flavonoids (myricetol, quercetol, campherole), pectins, calcium, iron, potassium, phosphorus, vitamin PP.
... Black currant (Ribes nigrum L.) seeds also possess acidic polysaccharides with anti-adhesive properties. High molecular weight galactans are responsible for the activity, by interacting with H. pylori adhesins [209] . ...
Article
Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy.
... Black currant (Ribes nigrum L.) is grown primarily for processing into juices, cordials and jams [1], and the seed and pomace are by-products for which uses in the functional food [2][3][4] and human health [5,6] sectors are being studied. After pressing the juice from the black currant, the pomace, including seed, is air-dried and the seed is selectively sieved out, leaving the seedless pomace waste consisting of skins and varying amounts of stalks and leaves. ...
Article
The nature of the fatty acids and other lipophilic components in extracts from black currant seed and pomace (containing seed) were investigated, with a view to highlighting any potential uses. The same non-hydroxylated fatty acids were the major components in both types of extract, but total levels were less in pomace (75 582 mg 100 g−1 oil) than in seed alone (90 972 mg 100 g−1 oil) and there were less unsaturated fatty acids, including GLA (8653 and 12 625 mg 100 g−1 oil, respectively), but long chain n-20:0 – n-30:0 fatty acids (4080 and 437 mg 100 g−1 oil, respectively) were greatly increased in pomace. Phytosterols (mainly β-sitosterol), saturated n-20:0 – n-30:0 policosanols, ω-hydroxy fatty acids (mainly 16-hydroxy 16:0) and 2-hydroxy fatty acids (mainly 2-hydroxy 24:0) were present at much greater levels in pomace (2496, 2097, 958 and 46 mg 100 g−1 oil, respectively) than in seed (553, 108, 161, and 1 mg 100 g−1 oil, respectively). The pomace extract is a useful source of fatty acids, phytosterols and policosanols with potential functional properties. Practical applications: The study investigated the lipophilic components in isohexane extracts from black currant seed and pomace (containing seed). Only pomace extracts had substantial amounts of phytosterols and policosanols that have potential as cholesterol-lowering agents, whereas fatty acids such as GLA, that has anti-inflammatory properties, are mainly in the seed.
... Historically, the identification of antiadhesive compounds against H. pylori has been based on the initial finding of antiadhesive properties of 39-sialyllactose [4]; unfortunately, this compound failed to prevent bacterial colonizaton of human stomach in a preliminary clinical study [5], likely owing to degradation of the compound under physiological conditions in the stomach. The search for additional antiadhesive compounds has yielded peptides [6], polyphenols [7][8], N-phenylpropenoyl-Lamino acid amides [9], and polysaccharides [10][11] that interact with bacterial outer membrane proteins (OMPs). The clinical and economic development of such antiadhesives is still underrepresented, in many cases because it is economically difficult to obtain sufficient amounts of these natural products at reasonable prices. ...
Article
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Traditional Asian and African medicine use immature okra fruits (Abelmoschus esculentus) as mucilaginous food to combat gastritis. Its effectiveness is due to polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach tissue. The present study investigates the antiadhesive effect in mechanistic detail. A standardized aqueous fresh extract (Okra FE) from immature okra fruits was used for a quantitative in vitro adhesion assay with FITC-labled H. pylori J99, 2 clinical isolates, AGS cells, and fluorescence-activated cell sorting. Bacterial adhesins affected by FE were pinpointed using a dot-blot overlay assay with immobilized Lewis(b), sialyl-Lewis(a), H-1, laminin, and fibronectin. (125)I-radiolabeled Okra FE polymer served for binding studies to different H. pylori strains and interaction experiments with BabA and SabA. Iron nanoparticles with different coatings were used to investigate the influence of the charge-dependence of an interaction on the H. pylori surface. Okra FE dose-dependently (0.2 to 2 mg/mL) inhibited H. pylori binding to AGS cells. FE inhibited the adhesive binding of membrane proteins BabA, SabA, and HpA to its specific ligands. Radiolabeled compounds from FE bound non-specifically to different strains of H. pylori, as well as to BabA/SabA deficient mutants, indicating an interaction with a still-unknown membrane structure in the vicinity of the adhesins. The binding depended on the charge of the inhibitors. Okra FE did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. Non-specific interactions between high molecular compounds from okra fruits and the H. pylori surface lead to strong antiadhesive effects.
... Within agar diffusion assay no direct cytotoxicity of the polysaccharide against H. pylori in the concentration range of 1 to 5 mg/mL was observed. On the other side, several reports have been published recently on polysaccharides from different origins with strong antiadhesive activities against H. pylori [18][19][20][21][22]; in these cases antiadhesion will result in inactivation of bacterial outer membrane proteins which are responsible for recognition of host cell surface structure and binding to the eukaryotic host cells. ...
Article
EPS1190 was isolated from skim milk fermented with Stretococcus thermophilus CRL1190. The polysaccharide consisted of 33% glucose and 66% galactose with 1,4- and 1,4,6-galactose residues as main building blocks beside a high amount of 1,4-linked glucose. The polymer was characterized additionally concerning viscosity and zeta potential. EPS1190 stimulated cellular vitality and proliferation of human stomach AGS cells and human buccal KB cells significantly. EPS1190 stimulated phagocytosis rate of murine macrophages RAW264.7 significantly. NO-release or anti-inflammatory effects by inhibition of LPS-induced NO release were not observed. Confocal laser scanning microscopy revealed that EPS1190 is partially internalized into AGS cells via endosomes. The bioadhesive absorption of FITC-labeled EPS1190 into the mucus layer on the apical side of the epithelium using histological tissue sections from human stomach was observed. Specific interaction of EPS1190 with mucin can be excluded as shown by microviscosimetry studies. EPS1190 increased the adhesion of H. pylori to AGS cells, which resulted in increased secretion of proinflammatory cytokines TNFa, IL-6 and IL-8. Summarizing, EPS1190 seems to stimulate epithelial cell regeneration and immunological innate defense mechanisms, which again can rationalized the use of this polysaccharide as cytoprotective compound in probiotioc preparations.
... There are very few reports on how fruit fibre can modulate gut microflora by altering their adhesion to the gut wall. Acidic polysaccharides isolated from blackcurrant seeds, when pre-incubated with Helicobacter pylori, were found to inhibit their adhesion to gastric mucosa (Lengsfeld et al., 2004). Kiwifruit is a rich source of fibre (Schrö der et al., 2001) whose gut health functionalities have not been adequately explored. ...
Article
The role of kiwifruit pectin as a functional food ingredient capable of beneficial gut health effects in vitro was investigated. Six different pectins were obtained from the kiwifruit cultivar Actinidia deliciosa ‘Hayward’ (ZESPRI™ GREEN) by selective re-solubilisation of the fruit fibre with different chemical treatments. The potential gut health benefit of kiwifruit pectin was tested with respect to its influence on bacterial adhesion to intestinal epithelial cells (Caco-2) in vitro. The most effective kiwifruit pectin (monoK pectin), obtained by re-solubilisation with monopotassium phosphate, was compared with three commercial functional polysaccharides - citrus pectin, guar gum and inulin. The monoK pectin was superior to inulin, a standard prebiotic in enhancing the adhesion of Lactobacillus rhamnosus and decreasing the adhesion of Salmonella typhimurium to Caco-2 cells. The adhesion of Bifidobacterium bifidum was significantly enhanced only by inulin and citrus pectin, while guar gum had no effect on adhesion of any of these bacteria.
... Furthermore, research was conducted on the fibre (Nawirska & Kwaśniewska, 2005), phytosterols (Yang, Koponen, Tahvonen, & Kallio, 2003), polyphenols (Lu & Foo, 2003) and the antioxidant potential of the seeds or the seed oils (Bushman et al., 2004;Parry et al., 2005). The protective effect of black currant seeds towards helicobacter pylori adhesion to the gastric mucosa of human was investigated by Lengsfeld, Deters, Faller, and Hensel (2004). Black currant seeds are recommended as edible inclusion in breakfast cereals (Tahvonen et al., 1998). ...
Article
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Berry seeds are distinguished by longevity though clear scientific appraisals cannot be made. Besides a hard seed coat other protecting substances are presumed in the seeds. Commonly the seeds are utilized as a source of oils. After pressing, there is a residue left that is still rich in bioactive ingredients. This paper gives an overview of the health-beneficial ingredients remaining in the residue of various berry seeds (bilberry, cranberry, rose hip, strawberry, elder, and black currant) with special focus on black currant. The fatty acid distribution and the content of fat, tocopherols and tocotrienols, phytosterols, carotenoids, vitamin C, fibre, protein, amino acids, dry matter, ashes, minerals, total phenols (gallic acid equivalent) and antioxidant capacity (TEAC) were determined. The investigation of berry seed press residues revealed that the total phenols and tocopherols were quantitatively the most important features of this material but there were significant differences between batches and cultures.
... For confirmation of these results an in situ assay on murine buccal mucosa sections was performed based on a protocol of [40,46]. Therefor bacteria were pretreated with test samples (only medium for untreated control group, TLCK (5 mM) for positive control, RA1 (100 μg/mL) for 90 minutes. ...
Article
Periodontitis is a disease with considerable impact on the whole organism and worldwide prevalence. The gram-negative bacterium Porphyromonas gingivalis is regarded as one of its main etiological agents. Essential for the progression of this disease are highly specialized virulence factors of P. gingivalis, Lys-gingipain (Kgp) and Arg-gingipain (Rgp). Both proteinases are involved in the process of adhesion to host cells, in the bacterial invasion into the cells, acquisition of nutrients and the modulation of the host's local immune response. In the context of developing oral hygiene products with antiadhesive activity against P. gingivalis a proanthocyanidin-rich acetone-water extract (7:3) of Rumex acetosa L. (Polygonaceae) [1] proved to be highly effective under in vitro conditions. Treatment of P. gingivalis with the extract led to concentration dependant gingipain inhibition. Especially Rgp activity was inhibited, by approximately 20, 60 and 80% at extract concentrations of 5, 10 and 50 µg/mL. For pinpointing active principles, dimeric and trimeric proanthocyanidins were isolated and their structural features characterized. Their influence on Kgp and Rgp activity was determined. While procyanidin B2 had no significant effect, epicatechin-3-O-gallate-(4b→8)-epicatechin-3-O-gallate showed about 80% inhibition of Rgp at a concentration of 5µM. An isolated A-type procyanidin, epicatechin-(2b→7, 4b→8)- epicatechin-(4b→8)-epicatechin, inhibited Rgp selectively, without influencing Kgp. Therefore unspecific tannin-like astringent effects as reason for gingipain inhibition can be excluded with the utmost probability. Corresponding structure-activity relations can be used for development of novel inhibitors of bacterial gingipains for oral application. Reference: [1] Bicker A, Petereit F, Hensel A (2009) Proanthocyanidins and a phloroglucinol derivative from Rumex acetosa L. Fitoterapia. 80(8); 483 – 95.
... However, our finding that IL-8 levels in TNFa-treated cells were unchanged in the presence of manuka honey (Fig. 1E) suggests that the effect of the honey might be antibacterial rather than antiinflammatory at the concentrations used in our experiments. H. pylori adherence is a precursor of CagA translocation and CagA-induced release of IL-8 in AGS cells (Lai et al., 2008) and there is evidence that carbohydrate-rich foods interfere with this process (Lengsfeld et al., 2004). Honey is essentially a complex mixture of sugars and our observation of significantly reduced IL-8 levels in the presence of 0.6% (v/v) manuka honey despite near normal bacterial growth (Fig. 1H) suggested that honey might affect the ability of H. pylori to adhere to AGS cells. ...
Article
Full-text available
Inflammation is widely recognized as a risk factor for gastric H. pylori-associated disease and disruption of this process provides a potential target for intervention. Using an in vitro system, broccoli sprouts, manuka honey and omega-3 oil, singly and in combination, were screened for their ability to limit H. pylori-associated inflammation. Each food significantly attenuated the release of IL-8 by H. pylori-infected cells, although the magnitude of this effect was variable. Only broccoli sprouts (0.125 mg/mL, w/v) were able to inhibit IL-8 release in response to TNFα, suggesting it acted by a different mechanism to the other two foods. The combination of manuka honey (1.25%, v/v) with omega-3 oil (0.006%, v/v) failed further to reduce IL-8 levels below those observed with honey alone, but the same concentrations of omega-3 oil and manuka honey independently enhanced the antiinflammatory effect of the isothiocyanate-rich broccoli sprouts. The results suggest that in the future certain foods may find increased clinical use as a non-antimicrobial approach for reducing the inflammation that is a major risk factor for H. pylori-associated disease, notably gastric cancer. Copyright © 2012 John Wiley & Sons, Ltd.
... Such molecules are currently investigated for treatment of Helicobacter pylori-associated diseases. [33][34][35][36] Currently, however, preventing UTI by anti-adhesion mechanisms is a concept brought forward only for cranberry products. This is reasonable, as there is strong evidence for cranberry-restricted A-type PAC as anti-adhesive compounds, sufficient evidence for PAC bioavailability in humans [29][30][31] and the preservation of anti-adhesive activity in the urine after oral ingestion. ...
Article
Full-text available
Rainer Nowack, Rainer Birck Nephrology/Dialysis Clinic, Lindau, Germany Abstract: Cranberry (Vaccinium macrocarpon) juice and extracts are widely used and recommended as folk remedy for prophylaxis of urinary tract infections (UTIs). Its putative mechanism is an anti-adhesive effect that prevents docking of bacteria on host tissues. The anti-adhesion quality is attributed to A-type proanthocyanidins (PACs), a group of polyphenols that has a restricted occurrence in cranberries and a few related plants. Clinical trials with cranberry have provided a mixed evidence on behalf of UTI prophylaxis. In some trials, a benefit could not be detected due to lower than calculated UTI recurrence rates, in others failure had retrospectively been blamed on underdosing of cranberry products. To circumvent such problems, cranberry products need to be standardized for the bioactive principle of PAC and administered at a sufficient dose. Further characterization of PAC bioavailability, improvement of the currently inconvenient prescriptions, and above all of the palatability for patients is strongly recommended. Larger staged trials should then be carried out in patients with relevant UTI risks. Keywords: cranberry (Vaccinium macrocarpon Aiton), urinary tract infection, proanthocyanidins, anti-adhesion, p-fimbriae
... Flavonoids [13][14][15] , anthocyanins 16,17 , tannins 18 , phenolic acids 15,16 , lignoids 19 and essential oils [20][21][22] have been found in Ribes species. Various biological activity studies have been reported about Ribes species such as antioxidant 13,16,[23][24][25][26][27][28] , anti-inflammatory 18,[29][30][31] , antihypertensive 32,33 , antiviral [34][35][36][37][38][39] , antimicrobial 24,[40][41][42][43][44][45][46] and antitumor 47,48 activities. Antiviral and antimicrobial researches have focused berries and products derived from berries of Ribes species, especially cultivated form of R. nigrum and R. rubrum; also R. alpinum and R. uva-crispa 24,40,43 . ...
Article
Full-text available
Leaves and branches extracts of eight Ribes species were evaluated for antiviral, antibacterial, antifungal and antimycobacterial activities. Antiviral activities of the extracts were evaluated against Bovine Herpes Virus Type-1 (BHV-1) (Cooper strain). Generally, the extracts showed cytotoxic effect. The lyophilized water extract of R. multiflorum branches showed antiviral activity with minimum and maximum CPE values 15.62 and 31.25 μg/mL, respectively. Antibacterial and antifungal activities of the extracts were screened against gram-negative bacteria (Klebsiella pneumonia, Escherichia coli), gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis) and fungi (Candida albicans and C. parapsilosis). The extracts showed antibacterial activity against gram-positive bacteria, especially against Staphylococcus aureus. However, no antifungal activity was detected. Lyophilized water extracts of leaves and branches of Ribes species were assessed for antimycobacterial activity against clinical isolate of Mycobacterium tuberculosis and M. tuberculosis H37Rv ATCC 27294. The extracts showed a stronger effect against M. tuberculosis H37Rv ATCC 27294 than clinical isolate of M. tuberculosis. To the best of our knowledge, this study is the first investigation of antiviral and antimycobacterial activities of Ribes species growing in Turkey.
... The antimicrobial activities of dietary plant bioactive compounds against pathogenic bacteria have been extensively reviewed by many authors [3,16,54]. Regarding the polysaccharides present in blackcurrant seeds, Lengsfeld et al. [40] in in vitro study observed a lower adhesion rate of Helicobacter pylori to gastric mucosa. The anti-adhesive properties of raw polysaccharides from BC seeds result from the presence of acidic high-molecular weight galactans, which are able to bind to H. pylori receptors, and thus can inhibit their ability to implementation in gastric epithelium. ...
Article
Blackcurrant (BC) is a well-known and appreciated berry fruit in our country and Poland is the largest BC producer among European Union countries and the second, after Russia, producer in the world. Due to the short shelf life of BC, its consumption in fresh form is relatively low , therefore the berries are processed into juices, jams, jellies, and freeze-dried products or alcoholic beverages. The high nutritional value of BC berries result from high content of bioactive compounds (among others, vitamin C, anthocyanins, pectins, organic acids, as well as polyunsaturated fatty acids contained in seeds of the fruit). Anthocyanins (ANTs) create the largest group among all polyphenolic compounds contained in BC. The results from different studies confirm that ANTs are important in attenuation oxidative stress parameters in the organism, and therefore can reduce the risk of certain non-communicable chronic diseases. Consumption of unprocessed and processed blackcurrants (i.e. juices and products containing fruit extracts) may support the nutrition therapy of cardiovascular diseases, certain eye diseases and may normalize the lipid profile of the blood plasma. Additionally, the beneficial profile of unsaturated fatty acids from BC seeds supports the therapy of autoimmune diseases. This article is attempts to summarize the results of the studies on the anti-inflammatory, immunomodulatory, anti-tumor and antimicrobial effects of BC bioactive compounds including the mechanisms of their action depending on the form of the fruit (e.g. juice, whole fruit extract, dried pomace, or seed oil). The article also highlights the potential use of BC in production of functional food, important in the dietary prevention of non-communicable chronic diseases resulting from increased oxidative stress in the organism.
... After extraction, the obtained dry extract was again extracted thrice with bidistilled water in the ratio of 1:25. The seed polysaccharides were precipitated with absolute alcohol, filtered, dialysed and lyophilized considering their inhibitory properties against Helicobacter pylori (Lengsfeld et al., 2004). Defatting is an essential process involved in the removal of fatty acids that are present in larger amounts to increase the availability of other bioactives, in this case polysaccharides. ...
Article
Seeds are the greatest storage reservoir of phytoconstituents, especially polysaccharides in which saccharides are one of the important constituents in our daily diet. Polysaccharides have messenger potential, act as biological carriers and have several medicinal values due to their complex chemical structure with diverse biological activities. Although the seed polysaccharides have been identified as potential pharmacological agents, they remain clandestine due to the cost incurred on processes such as extraction, isolation and purification. The aim of this review was to summarize the extraction and purification methods, structural characterization and biological activities of the seed polysaccharides. Classically, temperature- and pressure-dependent extraction techniques were exploited, but the developing technologies have paved the way for an easy and efficient recovery of pure seed polysaccharides. There are diversified seed polysaccharides with structural complexity and morphological differences. Thus, this review will give a new guidance on the different extraction and purification methods, structural characterization and biological activities for the production of seed polysaccharides.
... Indeed, ellagic acid, another polyphenol present in red and black berries, is known to exert antibacterial activity against H. pylori as well as other bacteria [17,51,52]. In addition, Lengsfeld et al. demonstrated that berryderived polysaccharides can combat H. pylori infection in vivo by preventing bacterial binding to the gastric mucosa [53]. Additional studies have shown antibacterial effects for berry-derived sanguiin H-6 [35] and rubusoside [54]. ...
Article
Full-text available
Helicobacter pylori infection is commonly treated with a combination of antibiotics and proton pump inhibitors. However, since H. pylori is becoming increasingly resistant to standard antibiotic regimens, novel treatment strategies are needed. Previous studies have demonstrated that black and red berries may have antibacterial properties. Therefore, we analyzed the antibacterial effects of black and red raspberries and blackberries on H. pylori. Freeze-dried powders and organic extracts from black and red raspberries and blackberries were prepared, and high-performance liquid chromatography was used to measure the concentrations of anthocyanins, which are considered the major active ingredients. To monitor antibiotic effects of the berry preparations on H. pylori, a high-throughput metabolic growth assay based on the Biolog system was developed and validated with the antibiotic metronidazole. Biocompatibility was analyzed using human gastric organoids. All berry preparations tested had significant bactericidal effects in vitro, with MIC90 values ranging from 0.49 to 4.17%. Antimicrobial activity was higher for extracts than powders and appeared to be independent of the anthocyanin concentration. Importantly, human gastric epithelial cell viability was not negatively impacted by black raspberry extract applied at the concentration required for complete bacterial growth inhibition. Our data suggest that black and red raspberry and blackberry extracts may have potential applications in the treatment and prevention of H. pylori infection but differ widely in their MICs. Moreover, we demonstrate that the Biolog metabolic assay is suitable for high-throughput antimicrobial susceptibility screening of H. pylori.
... Blackcurrant juice has antimicrobial properties, and its anthocyanins inhibit the adhesion of Typhimurium Salmonella to human epithelial colorectal adenocarcinoma cells (Caco-2) by up to 39% [73]. Polysaccharides from blackcurrant seed extracts are found to inhibit H. pylori adhesion to the human gastric mucosa [120]. Phenolic extracts (concentration 1 mg/mL) from blueberries, blackcurrants, raspberries, and strawberries can inhibit the growth of H. pylori [121]. ...
Article
Full-text available
Functional plant-based foods (such as fruits, vegetables, and berries) can improve health, have a preventive effect, and diminish the risk of different chronic diseases during in vivo and in vitro studies. Berries contain many phytochemicals, fibers, vitamins, and minerals. The primary phytochemicals in berry fruits are phenolic compounds including flavonoids (anthocyanins, flavo-nols, flavones, flavanols, flavanones, and isoflavonoids), tannins, and phenolic acids. Since berries have a high concentration of polyphenols, it is possible to use them for treating various diseases pharmacologically by acting on oxidative stress and inflammation, which are often the leading causes of diabetes, neurological, cardiovascular diseases, and cancer. This review examines commonly consumed berries: blackberries, blackcurrants, blueberries, cranberries, raspberries, black raspberries, and strawberries and their polyphenols as potential medicinal foods (due to the presence of pharmacologically active compounds) in the treatment of diabetes, cardiovascular problems, and other diseases. Moreover, much attention is paid to the bioavailability of active berry components. Hence, this comprehensive review shows that berries and their bioactive compounds possess medicinal properties and have therapeutic potential. Nevertheless, future clinical trials are required to study and improve the bioavailability of berries' phenolic compounds and extend the evidence that the active compounds of berries can be used as medicinal foods against various diseases.
... Within agar diffusion assay no direct cytotoxicity of the polysaccharide against H. pylori in the concentration range of 1 to 5 mg/mL was observed. On the other side, several reports have been published recently on polysaccharides from different origins with strong antiadhesive activities against H. pylori [18][19][20][21][22]; in these cases antiadhesion will result in inactivation of bacterial outer membrane proteins which are responsible for recognition of host cell surface structure and binding to the eukaryotic host cells. ...
Article
This work evaluated the ability of the probiotic Streptococcus thermophilus CRL1190 strain and its exopolysaccharides to adhere to gastric mucosa. Probiotic bacteria attachment to the human stomach epithelium was confirmed in human stomach tissue samples and the gastric epithelial cell line AGS. In addition, it was demonstrated that S. thermophilus CRL1190 strain reduced Helicobacter pylori adhesion and attenuated inflammatory response in AGS cells. This is the first demonstration of the capacity of S. thermophilus CRL1190 to adhere to the stomach gastric mucosa, and improve protection against H. pylori through the reduction of its adhesion and the modulation of the inflammatory response. Therefore, S. thermophilus CRL1190 fermented milk is a good candidate for further in vivo studying of the protective effect of functional food against H. pylori infection and gastric inflammatory damage.
... Napary z owoców i liści czarnej porzeczki (Ribes nigrum L.) stosuje się najczęściej w leczeniu dolegliwości ze strony układu krwionośnego (miażdżyca, nadciśnienie tętnicze), gorączki, krwawienia dziąseł i stanów zapalnych jamy ustnej oraz w łagodzeniu bólów żołądka (36,37). Wśród substancji izolowanych z owoców porzeczki wymienia się: nienasycone kwasy tłuszczowe, antocyjany, flawonoidy, pektyny, kwasy organiczne oraz polisacharydy (36,38). Zaobserwowano, że związki cukrowe izolowane z porzeczek mają zdolność do aktywacji makrofagów i hamowania wzrostu komórek nowotworowych, co zależne było od indukcji syntezy cytokin IL-2, IL-4, IL-10 oraz IFN-γ (39). ...
Article
Full-text available
The mucus layer that covers the stomach surface is a strongly hydrophilic colloid composed of numerous high molecular weight mucins. These glycoproteins play a key role in the protection against proteolytic enzyme activity and the acidic pH of gastric juice. They act as receptors for the mucosal microorganisms, including Helicobacter pylori. Adhesion of microorganisms to epithelial cells is essential for efficient colonization because it favors the virulence factors delivery to eukaryotic cells and prevents the microorganisms removal from the host organism. Because of this, disturbance of the interaction between bacteria and gastric mucosa sugar structures can protect against the development of infection. Polysaccharides derived from algae and plants have many useful features that increase their application, i.e. high stability, biodegradability, non-toxicity and ability to form gels. They show a number of beneficial biological activities including anti-inflammatory, antioxidant, immunomodulating, detoxifying and anti-adhesive. Therapy with polysaccharides isolated from algae and plants may be effective in reducing gastric mucosa inflammation and preventing H. pylori reinfection after completion of eradication therapy. Citation: Krzyżek P. [Algal and plant polysaccharides in the treatment of diseases caused by Helicobacter pylori]. Post. Fitoter. 2017; 18(3): 196-202.
... [55] Such outcome may especially benefit pregnant women where antibiotic treatment is not recommended. [56] Lengsfeld et al., [57] have also demonstrated that acidic high molecular weight galactans from blackcurrant seeds could inhibit adhesion of H. pylori to human gastric mucosa. An acidic polysaccharide from Aloe vera showed also a potent in-vitro anti-adhesive effect against H. pylori. ...
Article
Full-text available
Helicobacter pylori (H. pylori) is a worldwide infection that affects millions of people. Some people develop only minor symptoms or even no symptoms at all, whereas others complain of terrible stomach and chest pain, diarrhea, bloating, nausea, vomiting, heartburn, headaches, depression, anxiety and rashes. H. pylori can be eradicated by using conventional medical treatments or a natural approach. However, both approaches can also fail miserably due to patient incompliance and antimicrobial resistance of the infecting H. pylori strain. Therefore, a non-antibiotic agent that is both effective and free from side effects might be of considerable importance for the eradication of H. pylori.
... Lengsfeld et al. [20] have shown that adhesion of H pylori to human stomach sections was almost completely inhibited by pre-incubating H pylori with a fresh juice preparation of the fruit of the okra plant [Abelmoschus esculentus (L.) Moench]. Lengsfeld et al. [21] have also demonstrated that acidic high molecular weight galactans from blackcurrant seeds could inhibit adhesion of H pylori to human gastric mucosa tissue sections. Moreover, Lee et al. [22] have demonstrated the inhibition of H pylori adhesion by polysaccharide fractions of Panax ginseng and Artemisia capillaris to a human gastric adenocarcinoma epithelial cell line. ...
Article
AIM: To investigate the bactericidal and anti-adhesive properties of 25 plants against Helicobacter pylori (H pylori). METHODS: Twenty-five plants were boiled in water to produce aqueous extracts that simulate the effect of cooking. The bactericidal activity of the extracts was assessed by a standard kill-curve with seven strains of H pylori. The anti-adhesive property was assessed by the inhibition of binding of four strains of FITC-labeled H pylori to stomach sections. RESULTS: Of all the plants tested, eight plants, including Bengal quince, nightshade, garlic, dill, black pepper, coriander, fenugreek and black tea, were found to have no bactericidal effect on any of the isolates. Columbo weed, long pepper, parsley, tarragon, nutmeg, yellow-berried nightshade, threadstem carpetweed, sage and cinnamon had bactericidal activities against H pylori, but total inhibition of growth was not achieved in this study. Among the plants that killed H pylori, turmeric was the most efficient, followed by cumin, ginger, chilli, borage, black caraway, oregano and liquorice. Moreover, extracts of turmeric, borage and parsley were able to inhibit the adhesion of H pylori strains to the stomach sections. CONCLUSION: Several plants that were tested in our study had bactericidal and/or anti-adhesive effects on H pylori. Ingestion of the plants with anti-adhesive properties could therefore provide a potent alternative therapy for H pylori infection, which overcomes the problem of resistance associated with current antibiotic treatment.
... [55] Such outcome may especially benefit pregnant women where antibiotic treatment is not recommended. [56] Lengsfeld et al., [57] have also demonstrated that acidic high molecular weight galactans from blackcurrant seeds could inhibit adhesion of H. pylori to human gastric mucosa. An acidic polysaccharide from Aloe vera showed also a potent in-vitro anti-adhesive effect against H. pylori. ...
Article
Full-text available
Abstract: Helicobacter pylori (H. pylori) is a worldwide infection that affects millions of people. Some people develop only minor symptoms or even no symptoms at all, whereas others complain of terrible stomach and chest pain, diarrhea, bloating, nausea, vomiting, heartburn, headaches, depression, anxiety and rashes. H. pylori can be eradicated by using conventional medical treatments or a natural approach. However, both approaches can also fail miserably due to patient incompliance and antimicrobial resistance of the infecting H. pylori strain. Therefore, a non-antibiotic agent that is both effective and free from side effects might be of considerable importance for the eradication of H. pylori.
Article
Background Increasing drug resistance of Helicobacter pylori has highlighted the search for natural compounds with antiadhesive properties, interrupting the adhesion of H. pylori to stomach epithelia. Basella alba, a plant widely used in Asian traditional medicine, was investigated for its antiadhesive activity against H. pylori. Methods B. alba extract FE was prepared by aqueous extraction. Polysaccharides were isolated from FE by ethanol precipitation and arabinogalactan-protein (AGP) was isolated with Yariv reagent. Carbohydrate analyses was performed by standard methods and sequence analysis of the protein part of AGP by LC-MS. In vitro adhesion assay of fluorescent-labelled H. pylori J99 to human AGS cells was performed by flow cytometric analysis. Results Raw polysaccharides (BA1) were isolated and 9% of BA1 were identified as AGP (53.1% neutral carbohydrates L-arabinose, D-galactose, rhamnose, 5.4% galacturonic acid, 41.5% protein). After deglycosylation of AGP, the protein part (two bands at 15 and 25 kDa in tricine SDS-PAGE) was shown to contain peptides like ribulose-bisphosphate-carboxylase-large-chain. Histological localization within the stem tissue of B. alba revealed that AGP was mainly located at the procambium ring. Functional assays indicated that neither FE nor BA1 had significant influence on viability of AGS cells or on H. pylori. FE inhibited the bacterial adhesion of H. pylori to AGS cells in a dose dependent manner. Best anti-adhesive effect of ~67% was observed with BA1 at 2 mg/mL. Conclusion The data obtained from this study characterize in part the mucilage and isolated polysaccharides of B. alba. As the polysaccharides interact with the bacterial adhesion, a potential uses a supplemental antiadhesive entity against the recurrence of H. pylori after eradication therapy may be discussed.
Article
Unlabelled: On the basis of LC/UV/MS analysis, 35 compounds from the extracts of seeds of black, red, and white currants (2 cultivars of each) were identified. Black currants cultivars contained protocatechuic acid and p-hydroxybenzoic acid, and traces of nitril containing phenolic acids. The presence of synapoyl glucoside was characteristic for cv. Malling Jewel. Sesquiterpenoid glycosides and carboxymethylindol glycosides were present mainly in white and red currant cultivars. Blackcurrant seeds contained higher amounts of flavonoids, especially rutin, isoquercetin, and taxifolin. The currant seed extracts were tested for in vitro protective effect on chromosome aberrations in peripheral human lymphocytes using cytochalasin-B blocked micronucleus (CBMN) assay. The frequency of MN was scored in binucleated cells, and the cultivars of black currants showed the best antioxidant potential. At a concentration of only 0.17 mg/mL, extract of the seed cv. Malling Jewel effected a decrease in the frequency of MN of 60% compared with control cell cultures. Practical application: Our results provide evidence of protective effects of currant seed extracts and isolated pure compounds on cytogenetic damages in human lymphocytes. Thus, currant seed extracts could exert beneficial effects in quite a few diseases, for many of the biological actions have been attributed to their antioxidant properties.
Article
Dans cet article, l’auteur veut intéresser les acteurs de la phytothérapie à des plantes dont on ne parle que rarement et qui portent des fruits ou des baies qui ont eu une importance économique pour les populations des zones où elles poussent Ces baies, qui perdurent dans des contrées au climat difficile mais biologiquement assez protégées, ont des propriétés qui peuvent intéresser demain les amateurs de plantes alimentaires sauvages qui peuvent concourir à l’équilibre de leur santé. The author’s aim in this article is to raise awareness in phytotherapy professionals of little-known plants that produce fruit or berries with significant economic impact on populations living in the areas where they grow. These berries, which endure in countries with harsh, yet biologically wellprotected, climates, have properties that could interest supporters of wild food plants believed to contribute to maintaining stable health.
Article
Cranberry juice (Vaccinium macrocarpon) is a widely used and recommended North-American folk remedy for prophylaxis of urinary tract infections (UTI). Clinical trials have documented its efficacy in women with recurrent UTI, but so far not in other groups of patients. The composition of effective cranberry products and its dosage in UTI prophylaxis have not been defined. Intriguing experimental research has identified an anti-adhesive mechanism of cranberry juice that prevents docking of bacteria on host tissues. This efficacy mechanism can be traced in patients’ urine following oral intake of cranberry products and appears to be due to proanthocyanidins with an A-type linkage of flavanols. The application of this anti-adhesion mechanism of cranberry-proanthocyandins is currently also investigated in other common diseases of bacterial pathogenesis, for example Helicobacter pylori-associated gastritis and dental caries/periodontal disease. The use of cranberry products appears to be safe and provide additional benefits by anti-oxidant and cholesterol-lowering activity.
Article
In a previous study, high-molecular glycosylated compounds (polysaccharides and glycoproteins) from the immature fruits of the okra plant, Abelmoschus esculentus (L.) MOENCH, were shown to have a strong in vitro antiadhesive activity against Helicobacter pylori, leading to an inhibition of the binding to mucosal epithelia from human stomach in situ. For a further evaluation of okra compounds, aqueous extracts and polysaccharides were investigated concerning antiadhesive effects against the adhesion of Campylobacter jejuni on intestinal epithelia from chicken. In an in vitro adhesion model with fluorescent-labelled C. jejuni, the bacterial adhesion was shown to occur predominantly on jejunum and colon tissue, but only to a low extend on stomach, ileum and caecum tissue. Under these in vitro conditions, isolated okra polysaccharides strongly inhibited the microbial adhesion to colonic tissue. Within a controlled in vivo infection study over 42 days with chicken broilers infected by C. jejuni and fed with okra aqueous extract (50 and 100g/kg) no significant reduction in Campylobacter excretion was observed, indicating that intestinal decontamination is not possible by the oral application of these compounds.
Article
Cell adhesion mediated by cell adhesion molecules (CAMs) constitutes essential life phenomenon. In inflammation, immunity, infection, tumor, cardiovascular injury, and wound healing, cell adhesion comes into being the basic physiological and pathological process. Intervening with cell adhesion has been the important therapeutic and prophylactic strategies for diseases. Accumulated evidence has indicated that plant polysaccharides especially those exacted from Chinese traditional and herbal medicine (most of plant medicine) displayed various pharmacological effects such as anti-inflammation, antitumor, anti-infection, immunomodulation, cardiovascular protective effects, and so on. Focusing on cell adhesion, further research is expected to reveal the therapeutic mechanism of plant polysaccharides in disease processes.
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The article summarizes current data concerning distribution, major regions of cultivation, and new perspective pharmacological effects (anti-Alzheimer’s, neuroprotective, antitumour, antiviral, immunostimulant, hypolipidemic) of lemon balm (Melissa officinalis).
Article
Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. Bacterial adhesins affected were identified by overlay assay with immobilized ligands. 125I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects.
Article
Ethnopharmacological relevance: The genus Ribes Linn., which belongs to the Grossulariaceae family, contains 160 species distributed mainly in temperate and cold regions of the Northern Hemisphere. There are 59 species in southwest, northwest and northeast China. Some species of Ribes have been used as traditional and local medicines for the treatment of glaucoma, cardiovascular disease, stomachache, hepatitis, hyperlipidemia, hypertension and other ailments. However, the data provided in recent years have not been collated and compared. Aim of the study: This review aims to summarize the current status of ethnopharmacological uses, phytochemistry, pharmacology, clinical applications, and pharmacokinetics of the genus Ribes to better understand the therapeutic potential of the genus Ribes in the future and hope to provide a relatively novel perspective for further clinical application on the genus. Materials and methods: The literature on Ribes was collected through a series of scientific search engines including Elsevier, ACS, Springer, Web of Science, PubMed, Google Scholar, Baidu Scholar, Wiley, China National Knowledge Infrastructure (CNKI) and books. Results: Ribes species have been used for detoxification, glaucoma, cardiovascular disease, stomachache, hepatitis, hyperlipidemia, hypertension and other ailments. These plants mainly contain phenolic glycosides, flavonoids, proanthocyanidins, polysaccharides, etc. Most traditional uses are related to biological activity and have been confirmed by modern research. Pharmacological studies in vitro and in vivo revealed that the extracts and pure compounds possessed significant hypolipidemic, antioxidant, anti-inflammatory, antitumor, antibacterial, and antiviral activity, eyesight protection and other effects. Conclusions: The traditional uses, phytochemistry, pharmacology, pharmacokinetics, and clinical applications described in this article explained that the Ribes species has numerous activities, and these findings will promote further action in the area of mechanism research. However, very few preclinical and clinical studies have focused on the toxicology and pharmacokinetics of crude extracts and pure compounds from the genus Ribes. Moreover, several clinical evidence to support the health benefits of Ribes plants. The development of new medicines based on Ribes species as ingredients may be restricted. The pharmacological activity, clinical efficacy and safety of Ribes species need to be verified by systematic and comprehensive preclinical studies and clinical trials.
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Helicobacter pylori is an important bacterial pathogen that causes chronic infection of the human stomach, leading to gastritis, peptic ulcer disease and gastric cancer. Treatment with appropriate antibiotics can eliminate H. pylori infection and reduce the risk for severe disease outcomes. However, since H. pylori is becoming increasingly resistant to standard antibiotic regimens, novel treatment strategies are needed. Previous studies have demonstrated that black and red berries may have antibacterial properties. Therefore, we analyzed organic extracts and powders from black and red raspberries and blackberries and determined their antibacterial effects on multiple H. pylori strains. We used high-performance liquid chromatography to measure berry anthocyanins, which are considered the major active ingredients. To monitor antibiotic effects of the berry preparations on H. pylori , we developed a high-throughput metabolic growth assay based on the OmniLog™ system. All berry preparations tested had significant bactericidal effects in vitro , with MIC 90 values ranging from 0.49 to 4.17%. We next used human gastric epithelial organoids to evaluate biocompatibility of the berry preparations and showed that black raspberry extract, which had the strongest antimicrobial activity, was non-toxic at the concentration required for complete bacterial growth inhibition. To determine whether dietary black raspberry application could eliminate H. pylori infection in vivo , mice were infected with H. pylori and then were placed on a diet containing 10% black raspberry powder. However, this treatment did not significantly impact bacterial infection rates or gastric pathology. In summary, our data indicate that black and red raspberry and blackberry products have potential applications in the treatment and prevention of H. pylori infection, because of their antibacterial effects and good biocompatibility. However, delivery and formulation of berry compounds needs to be optimized to achieve significant antibacterial effects in vivo .
Article
Helicobacter pylori is the main pathogen that induces chronic gastritis, peptic ulcers, atrophic gastritis, and other gastric disorders, and it is classified as a group I carcinogen. To eradicate H. pylori infection, triple therapy consisting of two antibiotics and a proton pump inhibitor is the most widely recommended first‐line therapeutic strategy. Antimicrobial resistance to antibiotics contained in triple therapy could lead to therapeutic regimen failures. Recent studies showed that many natural products, including fruits, vegetables, spices, and medicinal plants, possess inhibitory effects on H. pylori, indicating their potential to be alternatives to prevent and manage H. pylori infection. This review summarizes the effects of natural products on H. pylori infection and highlights the mechanisms of action.
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Ribes nigrum is indigenous to central and northern Europe, Caucasus, Central Siberia and Himalaya.
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The results of studies of medicinal plants are given. The peculiarity their biology, physiology and phytochemistry, reproduction and cultivation, use in medicine and industry was considered.
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The bacterium Helicobacter pylori is recognized as the main causal agent of active chronic gastritis and peptic ulcer. For many years, traditional medicine has made use of several plants for the treatment of these afflictions; nevertheless, their possible effect upon the bacterium has just begun to be investigated. This study summarizes and analyzes the studies, conducted up to date, of plants with anti-H. pylori activity. It is proposed that their action on H. pylori is mainly directed to the depletion of bacterial population rather than to its eradication, as the current anti-ulcer therapy does. Plant species are presented as a very diverse source of bactericidal compounds, as well as for the development of new therapies for H. pylori control.
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Helicobacter pylori (H. pylori) is one of the leading causes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric adenocarcinoma. The current treatment of H. pylori infection with antibiotics and proton pump inhibitors has several limitations, including poor adherence and intrinsic patient-related factors, drug resistance, and the absence of adequate treatments. This review summarizes the current therapeutic approaches to eradicating H. pylori, the difficulties associated with its treatment, and several new perspectives aimed at improving existing treatment strategies.
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Colonization of the mucosa of the stomach and the duodenum by Helicobacter pylori is the major cause of acute and chronic gastroduodenal pathologies in humans. Duodenal ulcer formation strongly correlates with the expression of an antigen (CagA) that is usually coeexpressed with the vacuolating cytotoxin (VacA), a protein that causes ulceration in the stomach of mice. However, the relationship between these two virulence factors is unknown. To define whether CagA and VacA are coexpressed in all clinical isolates and their relationships, we collected 43 clinical isolates of H. pylori and studied their genetic and phenotypic properties. Based on this analysis, most of the strains could be classified into two major types. Type I bacteria had the gene coding for CagA and expressed the CagA protein and the vacuolating cytotoxin. Type II bacteria did not have the gene coding for CagA and did not express either the CagA protein or the vacuolating cytotoxin. Type I and type II bacteria represented 56 and 16%, respectively, of the 43 clinical isolates, while the remaining 28% had an intermediate phenotype, expressing CagA independently of VacA or vice versa. This finding shows that although it is present in most cytotoxic strains, CagA is not necessary for the expression of the vacuolating cytotoxin.
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Helicobacter pylori is a microaerophilic bacterium found in the stomach of asymptomatic humans as well as patients with acid peptic disease and gastric adenocarcinoma. We have developed an in situ adherence assay to examine the cell lineage-specific nature of binding of this organism and to characterize the nature of cell surface receptors that recognize its adhesin. Fluorescein isothiocyanate-labeled H. pylori strains were bound to surface mucous cells present in the pit region of human and rat gastric units but not to mucous neck, parietal, or chief cell lineages present in the glandular domains of these units. Binding was abolished by proteinase K treatment of tissue sections and by pretreatment of the bacteria with bovine submaxillary gland mucin, a rich source of fucosylated and sialylated carbohydrates. Several lines of evidence suggest that binding to surface mucous cells is not dependent upon terminal nonsubstituted alpha 2,3- and alpha 2,6-linked sialic acids in the adhesin receptor: (i) binding was not inhibited by incubating H. pylori strains with sialylated glycoconjugates such as fetuin and free sialyllactose; (ii) immunohistochemical stainings using the sialic acid-specific Sambucus nigra and Maackia amurensis lectins and the cholera toxin B subunit did not detect any sialylated glycoconjugates in these epithelial cells; and (iii) binding was not sensitive to metaperiodate under conditions that selectively cleaved carbons 8 and 9 of terminal nonmodified sialic acids. A role for fucosylated epitopes in the glycoprotein(s) that mediate binding of H. pylori to surface mucous cells was suggested by the facts that this lineage coexpresses the adhesin receptor and major fucosylated histo-blood group antigens, that monoclonal antibodies specific for histo-blood group antigens H, B, and Leb block binding, and that the lectin Ulex europaeus type 1 agglutinin, which is specific for alpha-L-fucose, also bound to the same cells that bound the bacteria. Furthermore, human colostrum secretory IgA inhibited adhesion in a metaperiodate- and alpha-L-fucosidase-sensitive but neuraminidase-independent fashion. The in situ adherence assay should be useful in further characterizing the H. pylori adhesin and its receptor and for identifying therapeutically useful compounds that inhibit strain-specific and cell lineage-specific binding of this human pathogen.
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Isolated for the first time in 1982 from human gastric biopsy, Helicobacter pylori is responsible for gastritis, peptic ulcer, and gastric cancer. A pathogenicity island acquired by horizontal transfer, coding for a type IV secretion system, is a major determinant of virulence. The infection is now treated with antibiotics, and vaccines are in preparation. The geographic distribution suggests coevolution of man and Helicobacter pylori.
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The total lipid content of fruit seeds of theRibes family ranges by weight from 18.3% in gooseberries (Ribes uva Crispa) to 30.5% in black currants (Ribes nigrum). Isolation procedures and analytical methods (gas chromatography, mass spectrometry, high performance thin layer chromatography and stereospecific analysis) demonstrate that the oils fromRibes seeds contain up to 19% by weight of γ-linolenic acid (γ-LA, C18∶3, n−6) in black currant oil. This lastRibes species thus constitutes one of the richest natural sources in γ-LA yet described. These oils appear promising for critically ill patients who seem unable to convert linoleic acid into subsequent EFA fractions.
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A polymethylene of molecular weight of 3.3 million was prepared by the catalytic decomposition of diazomethane. This polymer is highly crystalline and has a crystal melting point of 132°. This temperature is close to the convergence temperature for straight-chain paraffins. Some of the physical properties of the polymethylene are described and a mechanism of the polymerization is presented.
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Because previous studies have shown that a high molecular mass constituent of cranberry juice inhibited adhesion of Escherichia coli to epithelial cells and coaggregation of oral bacteria, we have examined its effect on the adhesion of Helicobacter pylori to immobilized human mucus and to erythrocytes. We employed three strains of H. pylori all of which bound to the mucus and agglutinated human erythrocytes via a sialic acid-specific adhesin. The results showed that a high molecular mass constituent derived from cranberry juice inhibits the sialic acid-specific adhesion of H. pylori to human gastric mucus and to human erythrocytes.
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A simple and rapid method is described for the preparation of alditol acetates from monosaccharides. It can be performed in a single tube without transfers or evaporations. Monosaccharides are reduced with sodium borohydride in dimethyl sulphoxide and the resulting alditols acetylated using 1-methylimidazole as the catalyst. Removal of borate is unnecessary and acetylation is complete in 10 min at room temperature. Monosaccharides are quantitatively reduced and acetylated by this procedure. The alditol acetates are completely separated by glass-capillary, gas-liquid chromatography on Silar 10C. The method has been applied to the analysis of monosaccharides in acid hydrolysates of a plant cell-wall.
Article
An improved procedure for the methylation analysis of oligosaccharides and polysaccharides is described. Steps in the procedure were examined and optimised for quantitative recovery and speed. Methylation was shown to be complete by using [14C]methyl iodide. All operations were performed in the same tube and the need to concentrate solutions containing acetylated alditols of methylated sugars was eliminated, thus minimising losses due to volatilization. The method is convenient, gives high recoveries of acetylated alditols of methylated sugars, and allows analysis of the glycosyl linkages of oligo- or poly-saccharides to be completed within a working day. A wide range of oligo- and poly-saccharides were methylated by this procedure.
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A microscale colorimetric assay for neutral sugars, in which neutral sugars react with resorcinol in the presence of 75% sulfuric acid solution is described. This assay, based on the use of microtiter plates with 96 U-shaped wells is simple and easy to handle; it allows accurate determinations with small samples (20 microliters) containing 1 to 100 nmol of neutral sugars and is quite convenient for detection of glycoconjugates in chromatographic column effluents.
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Reaction of hydroxy acids with water-soluble carbodiimides leads to the formation of lactones which can be reduced with sodium borohydride to the corresponding alcohols. In a similar manner polyuronides and glycosaminoglycuronans react with water-soluble carbodiimides. The exact nature of the products formed from the polymers has not been established but they appear to be lactones or intramolecular esters. These products can be reduced with sodium borohydride to convert the uronic acid residues in the polymers to the corresponding neutral sugars. Reduction facilitates acid hydrolysis of the acid-resistant glycosyluronic acid bonds in the polymer by replacing them with the more acid-labile glycosyl bonds. When hyaluronic acid, chondroitin sulfate, and heparin are subjected to this reduction and acid hydrolysis reaction sequence, more than 90% of the original uronic acid glycosidic bonds are cleaved. The remaining acid-resistant amino sugar glycosidic linkages are cleaved with nitrous acid to complete the essentially quantitative, nondestructive depolymerization of these polymers.
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A new method for determination of uronic acids with meta-hydroxydiphenyl is introduced. It is simpler, quicker, more sensitive, and more specific than other methods, and it needs lesser amounts of fluid. It is recommended for determination of acid mucopolysaccharides in biological materials.
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The total lipid content of fruit seeds of the Ribes family ranges by weight from 18.3% in goose-berries (Ribes uva crispa) to 30.5% in black currants (Ribes nigrum). Isolation procedures and analytical methods (gas chromatography, mass spectrometry, high performance thin layer chromatography and stereospecific analysis) demonstrate that the oils from Ribes seeds contain up to 19% by weight of gamma-linolenic acid (gamma-LA, C18:3, n-6) in black currant oil. This last Ribes species thus constitutes one of the richest natural sources in gamma-LA yet described. These oils appear promising for critically ill patients who seem unable to convert linoleic acid into subsequent EFA fractions.
Article
A particle agglutination assay (PAA) using fetuin (Ft) covalently coupled to carboxylate-modified latex (CML) particles was evaluated for rapid detection of sialic acid-specific haemagglutinins/lectins (SALs) of Helicobacter pylori isolates which bind sialoglycoconjugates. Sixty-three percent (20/32) of the isolates examined gave a positive PAA test. Cell-bound SALs were extracted by washing the bacteria with deionized water or isotonic saline, and their expression was influenced by pH and culture conditions. The Ft-CML reactivity of the PAA-positive isolates was inhibited by bovine submaxillary mucin, transferrin, fetuin, orosomucoid, vitronectin and lactoferrin in a manner which suggested that the isolates contain a lectin recognizing the alpha(2-6) linkage of terminal sialic acid. Western blots of strain NCTC 11637 SALs probed with horseradish peroxidase (HRP)-labelled Ft identified three bands (MW 64 kD, 62 kD, 56 kD) which also reacted with HRP-labelled mucin, transferrin, lactoferrin, orosomucoid, vitronectin and laminin. Sera from patients with a H. pylori infection and one polyclonal rabbit antiserum (strain NCTC 11637) also reacted with the SALs. Immunogold labelling of a polyclonal rabbit antiserum raised against the 64 kD protein of strain NCTC 11637 that reacted strongly with Ft-CML showed that abundant SALs were loosely cell-associated with the cell surface of both spiral and coccoidal forms of H. pylori. SALs were also present in low amounts on the surface of strain NCTC 11638 and 66, a clinical isolate that did not react with Ft-CML.
Article
Helicobacterpylori, the ulcer pathogen residing in the human stomach, binds to epithelial cells of the gastric antrum. We have examined binding of 13 bacterial isolates to epithelial cell lines by use of a sensitive microtiter plate method in which measurement of bacterial urease activity provides the means for quantitation of bound organisms. Several established human gastrointestinal carcinoma cell lines grown as monolayers were compared for suitability in these assays, and the duodenum-derived cell line HuTu-80 was selected for testing bacterial binding inhibitors. When bacteria are pretreated with oligosaccharides, glycoproteins, and glycolipids, a complex picture of bacterial-epithelial adherence specificities emerges. Among the monovalent inhibitors tested, 3'-sialyllactose (NeuAc alpha2-3Gal beta1-4Glc; 3'SL) was the most active oligosaccharide, inhibiting adherence for recent clinical isolates of H. pylori with a millimolar 50% inhibitory concentration (IC50). Its alpha2-6 isomer (6'SL) was less active. Most of the recent clinical isolates examined were inhibited by sialyllactose, whereas long-passaged isolates were insensitive. Among the long-passaged bacterial strains whose binding was not inhibited by 3'SL was the strain ATCC 43504, also known as NCTC 11637 and CCUG 17874, in which the proposed sialyllactose adhesin was recently reported to lack surface expression (P. G. O'Toole, L. Janzon, P. Doig, J. Huang, M. Kostrzynska, and T. H. Trust, J. Bacteriol. 177:6049-6057, 1995). Pretreatment of the epithelial monolayer with neuraminidase reduced the extent of binding by those bacteria that are sensitive to inhibition by 3'SL. Other potent inhibitors of bacterial binding are the glycoproteins alpha1-acid glycoprotein, fetuin, porcine gastric and bovine submaxillary mucins, and the glycolipid sulfatide, all of which present multivalent sialylated and/or sulfated galactosyl residues under the conditions of the binding assay. Consistent with this pattern, a multivalent neoglycoconjugate containing 20 mol of 3'SL per mol of human serum albumin inhibited bacterial binding with micromolar IC50. The H. pylori isolate most sensitive to inhibition by 3'SL was least sensitive to inhibition by sulfatide, gastric mucin, and other sulfated oligosaccharides. Bacteria that have been allowed to bind epithelial cells are also effectively detached by 3'SL. These results describe a heterogeneous adherence repertoire for these bacteria, but they also confirm the critical role of the 3'SL structure on human gastric epithelial cells as an adherence ligand for recent isolates of H. pylori.
Article
Helicobacter pylori NCTC11637 expresses a lipopolysaccharide (LPS) that comprises an O antigen side-chain with structural homology to the human blood group antigen Lewis X (Le(x)). The role of this molecule in adhesion of H. pylori to gastric epithelial cells was investigated. Mutants expressing truncated LPS structures were generated through insertional mutagenesis of rfbM and galE; genes encode GDP mannose pyrophosphorylase and galactose epimerase respectively. Compositional and structural analysis revealed that the galE mutant expressed a rough LPS that lacked an O antigen side-chain. In contrast, an O antigen side-chain was still synthesized by the rfbM mutant, but it lacked fucose and no longer reacted with anti-Le(x) monoclonal antibodies (Mabs). The ability of these mutants to bind to paraffin-embedded sections from the antrum region of a human stomach was assessed. Adhesion of the wild type was characterized by tropic binding to the apical surface of mucosal epithelial cells and cells lining gastric pits. In contrast, both the rfbM and galE mutants failed to demonstrate tropic binding and adhered to the tissue surface in a haphazard manner. These results indicate that LPS and, more specifically, Le(x) structures in the O antigen side-chain play an important role in targeting H. pylori to specific cell lineages within the gastric mucosa. The role of Le(x) in this interaction was confirmed by the tropic binding of synthetic Le(x), conjugated to latex beads, to gastric tissue. The observed pattern of adhesion was indistinguishable from that of wild-type H. pylori.
Article
The significance of acid-primed recognition of ligands by Helicobacter pylori urease is unknown. This study aimed to further characterize the specificity of urease adherence in vitro and verify whether specific inhibition will translate into in vivo suppression of colonization. A highly sensitive competitive enzyme-linked ligand capture assay was used to quantify the capacity of each test inhibitor to compete with labeled mucin for binding sites on immobilized native urease. A model polymer that strongly bound urease was used in an in vivo trial using euthymic hairless mice as an infection model. The blockage of urease-gastric mucin interaction by certain inhibitors revealed an acid-functional lectin-like activity by urease, specifically recognizing bacterial lipopolysaccharides and certain species of polysaccharides, nonbacterial glycolipids, and glycoproteins. Dextran sulfate significantly (P < 0.01) suppressed colonization of mice by H. pylori when given before and/or after challenge. The acid-driven high-affinity adherence of H. pylori urease to mucin and lipopolysaccharides contributes to gastric mucosal colonization by the bacterium based on in vivo targeting experiments using specific polysaccharides in a mouse model with acute infection. Acid-functional urease-homing polysaccharides that can interfere with urease-mucin or H. pylori whole cell-mucin interaction in vitro can significantly interfere with colonization by the bacterium in vivo.
Article
Because previous studies have shown that a high molecular mass constituent of cranberry juice inhibited adhesion of Escherichia coli to epithelial cells and coaggregation of oral bacteria, we have examined its effect on the adhesion of Helicobacter pylori to immobilized human mucus and to erythrocytes. We employed three strains of H. pylori all of which bound to the mucus and agglutinated human erythrocytes via a sialic acid-specific adhesin. The results showed that a high molecular mass constituent derived from cranberry juice inhibits the sialic acid-specific adhesion of H. pylori to human gastric mucus and to human erythrocytes.
Article
Fifteen anthocyanin structures are reported from an extract of black currant berries (Ribes nigrum L.). These are the 3-O-glucosides and the 3-O-rutinosides of pelargonidin, cyanidin, peonidin, delphinidin, petunidin, and malvidin, cyanidin 3-O-arabinoside, and the 3-O-(6' '-p-coumaroylglucoside)s of cyanidin and delphinidin. The anthocyanins were characterized by means of size exclusion chromatography, high-performance liquid chromatography, UV-visible spectroscopy, and electrospray mass spectrometry. The four main pigments (the 3-O-glucosides and the 3-O-rutinosides of delphinidin and cyanidin) made up >97% of the total anthocyanin content. The minor pigments were enriched from the extract by successive partition against ethyl acetate and by gel fractionation. These chromatographic steps were successfully used to isolate the acylated anthocyanins from the ethyl acetate layer and to separate cyanidin 3-O-arabinoside from the mixture of anthocyanins. The amounts of anthocyanin rutinosides were found to be higher than the amount of the corresponding glucosides for all detected pigments having the same aglycon moiety.
Article
In Asian medicine the fruit of the okra plant, Abelmoschus esculentus (L.) Moench., is used as a mucilaginous food additive against gastric irritative and inflammative diseases. To find a rational basis for its use against these diseases, several crude and purified carbohydrate-containing fractions from immature okra fruits were isolated and analyzed, and their effects against Helicobacter pylori in an in situ adhesion model on sections of human gastric mucosa were determined. Pretreatment of the bacteria with a fresh juice preparation inhibited the bacterial adhesion almost completely. Lyophilization and reconstitution of an extract solution led to a reduction of this effect. A crude polysaccharide (RPS) isolated from the fresh juice by ethanolic precipitation showed strong inhibitory effects. Further fractionation of RPS revealed a purified, highly acidic subfraction (AF III) with high antiadhesive qualities. Carbohydrate analysis revealed the presence of rhamnogalacturonans with a considerable amount of glucuronic acid, whereas other inactive subfractions contained little glucuronic acid or were glucuronic acid-free. After heat denaturation of the fresh juice or protein precipitation with 5% TCA the antiadhesive activity of the fresh extract was reduced, indicating that besides polysaccharides, protein fractions also exhibited antiadhesive properties. SDS-PAGE analysis of the precipitate revealed several bands of glycosylated proteins between 25 and 37 kDa that were almost diminished in the nonactive supernatant. Preincubations of gastric tissue with any of the active fractions did not lead to reduced bacterial binding. The antiadhesive activity is therefore due to the blocking capacity of specific Helicobacter surface receptors that coordinate the interaction between host and bacterium. Neither of the active fractions showed inhibitory effects on bacterial growth in vitro. The antiadhesive qualities of okra were assumed to be due to a combination of glycoproteins and highly acidic sugar compounds making up a complex three-dimensional structure that is fully developed only in the fresh juice of the fruit.
  • H D Behlitz
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Behlitz HD, Grosch W. Lehrbuch der Lebensmittelchemie. ; 4. Aufl Springer Verlag, Berlin, Heidelberg: 1985: 739
Anthocyanins from black currants (Ribes nigrum L.)
  • R Slimestad
  • H Solheim
Slimestad R, Solheim H. Anthocyanins from black currants (Ribes nigrum L.). J Agric Food Chem 2002; 50: 3228 ± 31
Rapid permethylation of glycolipids and polysaccharides, catalysed by sulfinyl carbanion in dimethylsulfoxide
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Hakamori SJ. Rapid permethylation of glycolipids and polysaccharides, catalysed by sulfinyl carbanion in dimethylsulfoxide. J Biochem 1964; 55: 205 ± 10
Helicobacter pylori virulence and genetic geography. Review
  • A Covacci
  • J L Telford
  • Del Giudice
  • G Parsonet
  • J Rappuoli
Covacci A, Telford JL, Del Giudice G, Parsonet J, Rappuoli R. Helicobacter pylori virulence and genetic geography. Review. Science 1999; 284: 1328 ± 33