Article

A novel compound from celery seed with a bactericidal effect against Helicobacter pylori

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Abstract

The aim was to purify and characterise an antimicrobial component from celery (Apium graveolens) seeds, which have been used for centuries as a herbal medicine with reported antibacterial effects. A crude alcoholic extract of celery seeds was fractionated by organic solvent extractions, column chromatography and HPLC. Fractions were assayed for antimicrobial activity against the gastric pathogen Helicobacter pylori and other bacteria. The purified antibacterial component was characterised via MS and NMR. Preliminary investigation of its mechanism of action included morphological studies, incorporation of macromolecular precursors, membrane integrity and two-dimensional protein electrophoresis. The purified component, termed 'compound with anti-Helicobacter activity' (CAH), had potent bactericidal effects against H. pylori; the minimum inhibitory concentration and minimum bactericidal concentration were 3.15 microg/ml and 6.25-12.5 microg/ml, respectively. CAH (M(r) = 384.23; empirical formula C(24)H(32)O(4)) had specific inhibitory effects on H. pylori and was not active against Campylobacter jejuni or Escherichia coli. MS and NMR data were consistent with a dimeric phthalide structure. The results appeared to rule out mechanisms that operated solely by loss of membrane integrity or inhibition of protein or nucleic acid synthesis. CAH may be suitable for further investigation as a potent agent for treating H. pylori infections.

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... Extracts from the fruits of Apium graveolens L. (Fructus Apii grave- olens, Celery fruits, sometimes also called Celery seeds, which is bota- nically incorrect) have been used in Ayurvedic medicine for treatment of urinary calculi, kidney stones, gut diseases and visceral spasms [1]; especially a wide traditional use is documented in traditional Persian medicine [2] for treatment of uncomplicated urinary tract infections (UTI). The herbal material is also used in traditional European phy- totherapy due to its diuretic activity and anti-inflammatory activity against UTI [3]. ...
... Preclinical in vivo data or clinical studies on positive effects of Celery fruit extracts for UTI have not been published until now, but reports on potential antimicrobial effects under in vitro conditions are available [1,4]. Within the last years investigations of new drug can- didates with antiadhesive properties against uropathogenic E. coli (UPEC) have been described, indicating that the blocking of bacterial outer membrane adhesins (especially FimH) effectively prevents in- fection of eukaryotic host cells by the pathogen [5][6][7][8][9]. ...
... In principle, female BALB/c mice were orally pretreated for 4 and 7 days with CSE (200 and 500 mg/kg/day). (Rational for choosing these dosage: according lit- erature the commonly used dose for Celery fruits is 3 × 1.5 to 2 g per day for humans [1], which corresponds to about 3 × 400 mg extract, equivalent to 17 mg/kg for humans; 200 mg/kg mouse corresponds to about 20 mg per animal). ...
Article
Fruits from Apium graveolens (Celery) are used traditionally in Persian and European medicine for the treatment of uncomplicated urinary tract infections. No data are available on A. graveolens extract on the interplay between uropathogenic E. coli and the eukaryotic host cells and on quorum sensing of the bacteria. The present study aimed to characterize an antiadhesive and anti quorum sensing effect of a characterized A. graveolens extract by specific in vitro assays and to correlate these effects with in vivo data obtained by an animal infection model. Hydroalcoholic extract CSE (EtOH-water, 1:1) from A. graveolens fruits was characterized by UHPLC/+ESI-QTOF-MS and investigated on antiproliferative activity against UPEC (strain NU14) and human T24 bladder cells. Antiadhesive properties of CSE were investigated within two different in vitro adhesion assays. For in vivo studies BALB/c mice were used in an UPEC infection model. The effect of CSE on bacterial load in bladder tissue was monitored within a 4- and 7 days pretreatment (200, 500 mg/kg) of the animals. CSE was dominated by the presence of luteolin-glycosides and related flavons besides furocoumarins. CSE had no cytotoxic effects against UPEC and bladder cells. CSE exerts a dose dependent antiadhesive activity against UPEC strains NU14 and UTI89. CSE inhibited in a concentration-dependent manner bacterial quorum sensing. 4- and 7-day pretreatment of animals with CSE transurethrally infected with UPEC NU14, significantly reduced the bacterial load in bladder tissue. CSE is assessed as an antiadhesive extract for which the traditional use in phytotherapy for UTI is justified.
... Feeding waste vegetables adds to the welfare of the animals and their meat quality. For example, betalains and folic acid from beets, anthocyanins from cabbage, and phenols, carotenoids and vitamin C from papaya all have health benefits [83][84][85][86][87][88][89][90][91][92]. ...
... Soil fertility and pasture health are also improved with pastured animals, including those in movable coops [85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100]. A system of floorless coops that are moved daily over permanent grass pasture permits poultry and rabbits to harvest a substantial portion of their diet. ...
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Organic farmers raise poultry and rabbits in British Columbia using ethnoveterinary remedies and natural feedstuffs. These ethnoveterinary practices were documented from interviews and a participatory workshop. This paper includes the plants used for respiratory conditions, nutrition and dental care of rabbits. Some of the plants have been used in animal and human health for centuries such as Echinacea spp., Chenopodium spp., Artemisia spp., and Nicotiana spp. Many of the plants used are also grown in the tropics and could be used there. Ethnoveterinary medicinal use can contribute to on-farm plant biodiversity.
... This is especially good for gout, where excess uric acid crystals collect in the joint. Its diuretic action may also relieve bladder disorders, cystitis and other kidney problem including stones and gravel (Aboud et al., 2014).Extracts from the fruits of Apium graveolens used in Ayurvedic medicine for treatment of urinary calculi, kidney stones, gut diseases and visceral spasms (Zhou et al., 2009), especially a wide traditional use is documented in traditional Persian medicine (Bahmani et al., 2016) for treatment of uncomplicated urinary tract infections (UTI). The herbal material is also used in traditional European phytotherapy due to its diuretic activity and anti-inflammatory activity against UTI (Apiifructus -Selleriefrüchte, 2016). ...
... graveolens is rich in phenolic compounds which serve as a good source of antioxidants (Jung et al., 2011). Extracts from the fruits of Apium graveolens have been used in Ayurvedic medicine for treatment of urinary calculi, kidney stones, gut diseases and visceral spasms (Zhou et al., 2009). ...
... The procedures employed for culture of H. pylori and analyses of anti-microbial activity were those previously described [34]. Cultures of H. pylori strains 3339 and 26695 [35] were obtained from Prof. David Kelly (University of Sheffield) and were obtained from H pylori patients with gastro-duodenal ulcers. ...
... Cultures of H. pylori strains 3339 and 26695 [35] were obtained from Prof. David Kelly (University of Sheffield) and were obtained from H pylori patients with gastro-duodenal ulcers. These were bacterially typed as described [34] Antimicrobial activity assays were performed using 24-well microplates. These were performed in multiple wells containing 0.1 mL of compound (diluted in DMSO) with 1.0 mL of early log phase H. pylori culture in Brucella broth with foetal bovine serum (as above). ...
Article
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Substituted 4-hydroxyquinolines were synthesized from anilines and diethyl 2-(ethoxymethylene)malonate by the Gould-Jacobs reaction via cyclization of the intermediate anilinomethylenemalonate followed by hydrolysis and decarboxylation. The 4-hydroxyquinolines reacted with phosphorous oxychloride to form 4-chloroquinolines, which reacted on heating with diethyl sodiomethylmalonate in DMF to yield moderate yields of substituted ethyl 2-(quinolin-4-yl)propanoates, many of which showed potent antimicrobial activity against Helicobacter pylori.
... This had led to severe problems in patients during or after treatment outcomes. Though there is certainly cause for concern, it is unfair to pass judgement on the Cameroon TM healing systems on the basis of their worst outcomes; concerns about romanticising the traditional practices have to be taken seriously (Nkongmeneck et al., 2007;Zhou et al., 2009) ...
... This has led to abuse of significant magnitude Uses and sale of products without any instruction or inset and poor labeling. Sales of products without any scientific studies on the active principles and safety (Zhou et al., 2009) Some fundamental problems on plant medicinal research are due to the fact that some indigenous researchers publish their works without any intellectual property rights. The level of protection of innovation and inventions in plants medicines is in total contradiction with the potentials of traditional pharmacopoeia, the knowledge of traditional medicine and dynamism of researchers (Bodeker, 1994;Achoundong et al., 2003). ...
Article
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Traditional medicine refers to health practices, approaches, knowledge and beliefs incorporating plant, animal and mineral based medicines, spiritual therapies, manual techniques and exercises, applied singularly or in combination to treat, diagnose and prevent illnesses or maintain well-being. In the last decade traditional medicine has become very popular in Cameroon, partly due to the long unsustainable economic situation in the country. The high cost of drugs and increase in drug resistance to common diseases like malaria, bacteria infections and other sexually transmitted diseases has caused the therapeutic approach to alternative traditional medicine as an option for concerted search for new chemical entities (NCE). The World Health Organisation (WHO) in collaboration with the Cameroon Government has put in place a strategic platform for the practice and development of TM in Cameroon. This platform aims at harmonizing the traditional medicine practice in the country, create a synergy between TM and modern medicine and to institutionalize a more harmonized integrated TM practices by the year 2012 in Cameroon. An overview of the practice of TM past, present and future perspectives that underpins the role in sustainable poverty alleviation has been discussed. This study gives an insight into the strategic plan and road map set up by the Government of Cameroon for the organisational framework and research platform for the practice and development of TM, and the global partnership involving the management of TM in the country.
... Cameroon has not had the opportunity to develop a single eye phytomedicine. Tde country rely more on the purchase of imported pharmaceutical products with an outcome of heavy losses of state revenue, and unfortunately the development policy has not been geared towards available local resources (mainly medicinal plants) [34][35][36][37]38]. Government late move in policy in Cameroon to provide health care services to the population indicates the inability of government to ensure provision of quality services at an affordable price to everyone and particularly to the most vulnerable groups [4,39]. ...
... They are respected members of their communities and live and work in the most rural areas. They are the most commonly consulted and most accessible primary health care providers in all African communities [38,42]. ...
Article
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Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome that is characterized by chronic hyperglycaemia, and can lead to chronic long-term complications. The prevalence of diabetes mellitus in Cameroon has been reported at 5.9% in 2017. Studies conducted in 2011, showed that only 41% of patients had a good glycaemic control which was, HbA1c < 6.5. The aim of this study was therefore to evaluate the treatment intensification with time in T2DM patients in the Yaoundé diabetic Centre in Cameroon. Methods: The study was a cross-sectional analytical study. In a group of T2DM patients followed up at the National Obesity Centre (NOC) with poorly controlled blood sugar (HbA1c ≥ 7%). The treatment intensification and outcome were evaluated between the periods January 2016 to April 2018. The data was collected from patients’ medical booklet and through a face-to-face interviewer-administered questionnaire. Results: One hundred and eleven patients (31 males, 27.9% and 80 females, 72.1%) were recruited. The mean age was between 59 ± 10 years and the mean duration of diabetes 8.6 ± 7.0 years. The patients’ treatment consisted: 1) oral anti-diabetic (OAD) agents, monotherapy (24.3%), bitherapy (28.8%), tritherapy 2.7%, 2) insulin only, 19.8% and 3) insulin mixture, 24.3%. The mean baseline HbA1c was 9.3 ± 2.0%. Within the given follow-up time of 16 [11-21] months, only 40 out of the 111 patients had their treatment intensified and 71 had no intensification (therapeutic inertia) despite poor HbA1c levels. Among the 40 with intensification, 5 had immediate intensification and the proportions according to intensification delay ≤3 months, 3-6 months, 6-12 months and >12 months . Conclusion: Therapeutic inertia affected two third of our population. Despite the high level of inertia, both patients with intensified treatment and non-intensified treatment reached treatment targets.
... Cameroon has not had the opportunity to develop a single eye phytomedicine. Tde country rely more on the purchase of imported pharmaceutical products with an outcome of heavy losses of state revenue, and unfortunately the development policy has not been geared towards available local resources (mainly medicinal plants) [34][35][36][37]38]. Government late move in policy in Cameroon to provide health care services to the population indicates the inability of government to ensure provision of quality services at an affordable price to everyone and particularly to the most vulnerable groups [4,39]. ...
... They are respected members of their communities and live and work in the most rural areas. They are the most commonly consulted and most accessible primary health care providers in all African communities [38,42]. ...
Article
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Herbal plants have played an important role traditional medicine therapy of multiple human illnesses since the existence of man in many parts of the globe .The most common eye diseases include conjunctivitis, cataract, glaucoma, eye allergies, eye inflammation. The problem of adverse drug effects of modern drugs, has led to the increased use nowadays of herbal remedies in the treatment of eye diseases. The World Health Organization (WHO), defines traditional medicine as, the knowledge, skills and practices based on theories, beliefs, and experiences indigenous to diverse cultures, be it explicable or not that are used in the maintenance of health and the prevention, diagnosis, improvement and the treatment of physical and mental diseases. In the last decade, the use of traditional medicine has gained popularity and has expanded globally. While traditional medicine is used in developing countries for primary health care, it is also being used in developed countries with advanced health care systems. Traditional medicine accounts for up to 60% of health care delivered in Cameroon, while in other African countries traditional medicine is being relied on as a result of cultural and historical beliefs and up to 80 % of the population in Africa use traditional medicine to meet their health care needs. Although, traditional medicine is widely used, issues around policy; safety; efficacy and quality control are still of prime public health concern. Traditional eye care practices are believed to be indigenous medicines used by community members for the treatment of eye diseases or ocular problems. This is the most applied form of eye treatment in Africa and other parts of Asia and Latin America. Eye care is a public health concern in Cameroon due to late diagnosis of eye pathology and limited access to medication and affordability of prescription eye glasses. This paper attempts to review the herbal medicine practice as an alternative approach to eye treatment using traditional healing, and the development of eye health promotion strategies in the primary health care system in Cameroon.
... (syn. Piper lenticellosum C.D.C.) (Piperaceae), widely used in folk medicine in tropical and subtropical South American countries and known for their anti-inflammatory and anti-ulcer action (Quilez et al., 2010); 'compound with anti-Helicobacter activity', extracted from celery (Apium graveolens) seeds (Zhou et al., 2009); and phenolic acid derivatives, acylglycoflavonoids and condensed tannins from Davilla elliptica and Davilla nitida (Kushima et al., 2009). Resveratrol, a polyphenol highly abundant in red grapes (Daroch et al., 2001) (Zaidi et al., 2009), exhibits anti-inflammatory and anti-cancer activity and has cardioprotective and neuroprotective properties (Mahady & Pendland, 2000). ...
Article
Helicobacter pylori is a common human pathogen infecting about 30% of children and 60% of adults worldwide and is responsible for diseases such as gastritis, peptic ulcer and gastric cancer. Treatment against H. pylori is based on the use of antibiotics, but therapy failure can be higher than 20% and is essentially due to an increase in the prevalence of antibiotic-resistant bacteria, which has led to the search for alternative therapies. In this review, we discuss alternative therapies for H. pylori, mainly phytotherapy and probiotics. Probiotics are live organisms or produced substances that are orally administrated, usually in addition to conventional antibiotic therapy. They may modulate the human microbiota and promote health, prevent antibiotic side effects, stimulate the immune response and directly compete with pathogenic bacteria. Phytomedicine consists of the use of plant extracts as medicines or health-promoting agents, but in most cases the molecular mode of action of the active ingredients of these herbal extracts is unknown. Possible mechanisms include inhibition of H. pylori urease enzyme, disruption of bacterial cell membrane, and modulation of the host immune system. Other alternative therapies are also reviewed.
... Heliotropium europaeum (heliotrope), which contains potent hepatotoxic pyrrolidine alkaloids, is often confused with Valeriana officinalis (garden heliotrope) known to contain valepotriates with sedative and muscle relaxant properties. Therefore, effective monitoring of safety of herbal medicine requires effective collaboration between botanists, phytochemists and pharmacologists [15]. ...
... Celery (Apium graveolens) is commonly used as food, but it could also be used as a source of exogenous natural antioxidant [5]. Celery extract (CE) contains flavonoids and phenolic compounds that not only inhibit reactive oxygen species (ROS) during inflammation [6] but also restrain bacterial colonization [7]. The management of MRSA colonization using exogenous antioxidants promotes faster healing in the skin wound through the activation of anti-inflammatory mechanisms and cell activation. ...
Article
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Background and Aim: Antimicrobial resistance is a global problem caused by extensive utilization of antibiotics that promote gene resistant among bacteria, including Staphylococcus aureus. This study aimed to analyze the potential effects of celery (Apium graveolens) extract as an antioxidant and antimicrobial agent against methicillin-resistant S. aureus (MRSA), in vitro and in vivo. Materials and Methods: Celery was extracted and tested against a MRSA isolate in vitro. The minimum inhibitory concentration (MIC) against MRSA for the celery extract (CE) was determined to be 0.1% and it was formulated into a cream. A total of 30 female Sprague Dawley rats were divided into five groups: Group 1, negative control; Group 2, positive control; Group 3, treated with 0.05% CE cream; Group 4, 0.1% CE cream; and Group 5, 0.2% CE cream. All animals in the groups were exposed to a full-thickness skin biopsy on the dorsal portion, and they were infected with 30 μL of 105 colony-forming units of the MRSA isolate. The treatment was administered twice a day for 7 days. The skin samples were collected on days 3 and 7 after the treatment. The skin tissue was examined histologically using hematoxylin and eosin, Gram staining, and immunohistochemistry against cytokeratin (CK)-17. Results: Results showed that 0.2% of CE cream was the best treatment for wounds infected with MRSA. CE (0.2%) cream increased skin reepithelialization, fibroblast proliferation, and CK-17 expression; it also decreased the percentage of wound area, inflammatory cell infiltration, and bacterial colonization in skin wound tissue compared to the other treatments (p≤0.05). Conclusion: This study demonstrated that celery could be utilized as an alternative herbal therapy against MRSA-associated skin infections.
... The plants of the Apiaceae (Umbelliferae) family remain in use through thousands of years ( Zhou et al., 2009). For instance, celery (Apium graveolens L.) seeds were firstly mentioned by Aulus Cornelius Celsus in 30 A.D., to be used to decrease the pain (Murti, Abidin, & Yusof, 2013). ...
Article
Apiaceae plants exhibit a broad spectrum of activities, for instance, antithrombotic, hypotensive, antioxidant, and insecticidal. They also provide a source of phthalides, which display antimicrobial activity. Considering the fact of rising resistance of both bacteria and fungi against commonly used antibiotics, developing of new naturally derived compounds is undeniably attractive approach. To our best knowledge, there are no other reviews concerning this subject in the literature. In view of above, an attempt to summarize an antimicrobial potential of isolated compounds and extracts from Apiaceae plants has been made, by specifying techniques of activity determination and methods of extraction. Techniques of antimicrobial activity evaluation are mainly based on bioautography, diffusion, and dilution methods. Therefore, we focused on in vitro data described in literature so far.
... 4. Determination of purity of the fractions A-The fraction obtained from column were applied on TLC plates separately. TLC plates (GF 254, Merk Germany) and the mobile phase was hexane -ethyl acetate (7:3) (Zhou et al., 2014). B-Gas chromatography was done in a gas chromatography (hp, model 6890), equipped with a flam ionization detector, manual injection, HP5 fused silica column (5% phenylmethyl polysiloxane), 30 m , 0.25 mm i.d., film thickness 0.25 mm, and hp ChemStation software system, temperature of oven was adjusted at 60 ℃, raising at 3 ℃ per mint to 250 ℃ and then held 20 min at 250 ℃; injector temperature: 250 ℃; carrier gas: helium at 1.0 mL per min; splitting ratio 1: 10; detectors temperature: 300℃ (Marongiu et al., 2013). ...
... Experimental studies on rodents have proved anti-inflammatory effect and antiulcer property of seed extract of A. graveolens [64,65]. A phthalide dimer isolated from the alcoholic extract of A. graveolens (A-CSE) inhibited the action of Helicobacter pylori which is a causative factor for peptic ulcer [66]. ...
Article
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Plant based traditional medicine system occupies a key role in treating various disease conditions. Medicinal plants are considered to be the backbone of herbal medicine as they contain several unique bioactive compounds. Herbal medicines have been used extensively in both tropical and subtropical places for curing and treating medical ailments. Herbal medicines are formulated using different parts of a plant. The active components present in different parts of the plant work synergistically to fight against several diseases. Celery (Apium graveolens; family Apiaceae) is used as a medicinal agent in Ayurveda and Unani medicine system. Scientific evidence indicates that leaf, stem, root and seed extracts of celery are reported to possess remarkable medicinal properties. Seeds are also important in human nutrition as they are a rich source of fatty acids, proteins, phytochemicals and micronutrients. Active compounds such as alkaloids, coumarins, flavonoids, glycosides, limonene, myrcene, phenols, phthalides, and steroids present in celery seeds are responsible for different medicinal properties. Medicinal properties of celery seeds include anticancer, antidiabetic, anti-hyperlipidemic, antioxidant, antimicrobial and anti-inflammatory activity. This review paper provides information on phytochemical constituents and medicinal properties of celery seeds that provide further research opportunities to unravel and exploit other unknown medicinal properties of celery seeds for the optimal benefit of mankind.
... The purified component, termed (CAH), isolated from the crude alcohol extract of celery (Apium graveolens L., Apiaceae) seeds, had potent bactericidal effects against H. pylori; the MIC and MBC were 3.15 lg/ml and 6.25–12.5 lg/ml, respectively . CAH formula is C 24 H 32 O 4 with a dimeric phthalide structure (Zhou et al., 2009). All part (root, stem, leaf, seed, and pod) extracts of Impatiens balsamina L., Balsaminaceae exhibited bactericidal activity against H. pylori. ...
Article
Ulcerative colitis is an inflammatory chronic disease that affects the mucosa and submu-cosa of the colon and rectum. Several types of drugs are available such as aminosalicylates. Peptic ulcer disease (PUD) is a common disorder that affects millions of individuals worldwide and it can be considered one of the most important common diseases in the world. Treatment of peptic ulcers depends on using a number of synthetic drugs that reduce the rate of stomach acid secretion (Anti-acids), protect the mucous tissues that line the stomach and upper portion of the small intestine (Demulcents) or to eliminate Helicobacter pylori (H. pylori). In most cases, incidence of relapses and adverse reactions is seen in the following synthetic antiulcer therapy. Accordingly, the main concern of the current article is to introduce a safe drug (or more) of natural origin, to be used for the management of gastric ulcers without side effects. A widespread search has been launched to identify new anti-ulcer therapies from natural sources. Herbs, medicinal plants, spices, vegetables and crude drug substances are considered to be a poten-tial source to control various diseases including gastric ulcer and ulcerative colitis. In the scientific literature, a large number of medicinal plants and their secondary metabolites with potential anti-ulcer (anti-peptic ulcer and antiulcerative colitis) activities have been reported. Treatment with nat-ural products produces promising results and fewer side effects. Our goal is to collect the published
... 51 The "compound with anti-Helicobacter activity" isolated from the alcoholic extract of seeds, according to NMR and MS data, of a dimeric phthalide structure, has a strong bactericidal effect against H. pylori, exhibiting a strong anti-adhesive activity. 54,55 The methanol extract also showed 100% mortality for nematodes and mosquito larvae. 56 Antiulcer, antisecretory and cytoprotective properties of A. graveolens are known. ...
Article
Phytochemical composition data of various parts of celery (Apium graveolens L.) and pharmacological activity thereof are analyzed herein. Flavonoids, organic acids, hydroxycinnamic acids, ether oil terpenoids, tannins, vitamins and microelements are A. graveolens biologically active substances (BAS). Rich composition of BAS causes multiple both biological and pharmacological effects of herbal raw materials extracts mainly due to antioxidant activity. Furthermore, the extracts have neuroprotective, anti-inflammatory, hypolipidemic, antihypertensive and antibacterial effects. A. graveolens possesses wide spectrum of pharmacological activities and is a nontoxic plant; A. graveolens-based medicines will have high margin of safety. The results obtained provide opportunities for making herbal pharmaceutical celery-based substances and introduction thereof into the academic medicine.
... An MIC value of 100 µg/ml by 8-geranyloxy psoralenrich hexane extract of Prangos uloptera roots was able to inhibit growth of Staphylococcus epidermidis and Candida kefyr (Razavi et al., 2009). Against Gram-negative bacteria, a purified component from ethanol extract of celery (Apium graveolens) seeds had an activity against Helicobacter pylori at 3.15 µg/ml MIC and 6.25-12.5 µg/ml MBC (Zhou et al., 2009). Antiplasmodial activity against Plasmodium falciparum was assessed by hexane extract of Ferula pseudalliacea roots, rich in sanandajin, with an IC 50 value of 2.6 µM (Dastan et al., 2012). ...
Article
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The objective of this work was to examine the phytochemicals present in different aqueous and organic extracts from different organs of Daucus crinitus Desf. and to evaluate their antimicrobial activity. Phytochemical screening was done to characterize the secondary metabolites in various solvent extracts, and antimicrobial activity was evaluated by agar disk diffusion and broth microdilution to determine inhibition zone diameters and MICs. A remarkable antimicrobial effect was observed in organic extracts of stems and seeds (MIC = 0.31-0.83 mg/ml on S. aureus, B. cereus, and C. albicans) containing many phytochemical families such as coumarins, flavonoids, reducing sugars, steroids, tannins, and terpenes. Daucus crinitus may be a good source of bioactive molecules endowed with antimicrobial activity.
... Friedmen (2002) showed that celery seed extracts have bactericidal activities against Campylobacter jejuni, Escherichia coli, Listeria monocytogenes and Salmonella enterica (Friedman 2002), while a methanolic extract has antifungal, mosquitocidal and nematicidal activities (Momin et al. 2000;Momin and Nair 2001). Recently, Zhou et al. (2009) showed that the alcoholic extract of celery seed (A-CSE) and a phthalide dimer isolated from this extract inhibited Helicobacter pylori in vitro (Rainsford and Liu 2006). ...
Article
An extract of the seed from celery (Apium graviolens) (CSE), and fractions thereof, have been found to possess anti-inflammatory activity, gastro-protective activity, and anti-Helicobacter pylori activity. In view of the potential for employing these extracts for therapeutic use, toxicological investigations were undertaken with an alcoholic extract (A-CSE) which has previously been shown to have the above pharmacological activities. A 28-day toxicity study was performed in rats according to Good Laboratory Practice (GLP) conditions. Eighteen adult male and 18 adult female rats were randomly assigned to 3 treatment groups of 6 rats/sex/group and were dosed orally with A-CSE of 0, 150 or 5,000 mg/kg per day. Daily observations of vital signs and body weights were recorded and ophthalmological investigations were performed. At autopsy, the principal organs were weighed and sections collected for histological analysis. Serum and urine samples were collected at termination for routine clinical chemistry. Under non-GLP conditions alpha-2-μ-globulin immunohistochemistry was performed on kidney tissues and hepatic cytochrome P450 protein was determined, as well as, the enzymatic activities of the principal isoforms. All animals survived treatments with no visible or behavioral signs of toxicity being observed during the study. There were no statistically significant differences in body weight gains, body weight gains per day or cumulative absolute body weight gains, for either sex, in any treatment groups when compared with controls. Slightly increased liver weight and liver to body and brain weight ratios were observed in female rats and in liver to body weight ratios in male rats given high dose A-CSE which was a test article effect, but the absence of any microscopic correlates for the liver weight increases suggests that these were not toxicologically significant. Treatment related macroscopic changes were not observed at necropsy and microscopic findings were limited to minimal increases in gastric eosinophils in several male and female rats in the 5,000 mg/kg per day treatment groups. Minimal focal degeneration of renal tubules was observed sporadically in both sexes assigned to all treatment groups including control and was consistent with early spontaneous nephropathy of laboratory rats and thus was not considered to represent a pathologic change associated with the test article. Increased serum globulin and phosphorus levels were observed in male rats given 5,000 mg/kg per day A-CSE and decreased serum triglycerides levels in female animals given 150 or 5,000 mg/kg per day A-CSE. The increase in serum globulin and phosphorus in male animals was small in magnitude and not considered toxicologically significant. The mechanism for the decrease in serum triglycerides in female rats was not apparent. Changes in urinalysis parameters were limited to small decreases in urine pH in female animals in the 150 and 5,000 mg/kg per day groups and were not deemed toxicologically significant. Alpha-2-μ-globulin immunohistochemistry was performed on kidney tissues from all animals and found to be within normal physiologic limits. Minor corneal mineralization occurred in some animals from all treatment groups. Cataracts were observed in one in the control and one in an animal that had 5,000 mg/kg per day but since the cataracts occurred in the metabolically inactive region of the lens, these were not considered indicative of test article related lesions. There were no changes in total hepatic microsomal protein or in total cytochrome P450 protein. Although male rats appeared to have to higher levels of total microsomal protein than female rats, there appeared to be no treatment effect in either male or female animals. As regards the activity of the various isoforms tested (CYP2B1/2, CYP1A1/2, CYP3A1/2), with the large range of activities detected for each P450 isoform, no clear change in activity or protein were observed, however, these data were not statistically analyzed. These results suggest that there are no toxicologically significant sub-chronic effects of oral A-CSE in rats. The no adverse effect level for systemic toxicity would appear to be 5,000 mg/kg per day.
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Helicobacter pylori (H. pylori) successfully colonizes the human stomach of the majority of the human population. This infection always causes chronic gastritis, but may evolve to serious outcomes, such as peptic ulcer, gastric carcinoma or mucosa-associated lymphoid tissue lymphoma. H. pylori first line therapy recommended by the Maastricht-4 Consensus Report comprises the use of two antibiotics and a proton-pomp inhibitor, but in some regions failure associated with this treatment is already undesirable high. Indeed, treatment failure is one of the major problems associated with H. pylori infection and is mainly associated with bacterial antibiotic resistance. In order to counteract this situation, some effort has been allocated during the last years in the investigation of therapeutic alternatives beyond antibiotics. These include vaccines, probiotics, photodynamic inactivation and phage therapy, which are briefly revisited in this review. A particular focus on phytomedicine, also described as herbal therapy and botanical therapy, which consists in the use of plant extracts for medicinal purposes, is specifically addressed, namely considering its history, category of performed studies, tested compounds, active principle and mode of action. The herbs already experienced are highly diverse and usually selected from products with a long history of employment against diseases associated with H. pylori infection from each country own folk medicine. The studies demonstrated that many phytomedicine products have an anti-H. pylori activity and gastroprotective action. Although the mechanism of action is far from being completely understood, current knowledge correlates the beneficial action of herbs with inhibition of essential H. pylori enzymes, modulation of the host immune system and with attenuation of inflammation.
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Background: Apium graveolens L. (commonly known as celery) seeds have been used traditionally to treat a variety of conditions including bacterial infections and inflammation. There is also considerable recent interest in its use as a complementary medicine. However, they are yet to be tested for the ability to inhibit the growth of bacterial triggers of autoimmune diseases. Methods: Antimicrobial activity was assessed using disc diffusion and liquid dilution minimum inhibitory concentration (MIC) assays against a panel of bacterial triggers of some autoimmune diseases. Interactions between the A. graveolens extracts and conventional antibiotics were studied and classified using the sum of the fractional inhibitory concentration (∑FIC). Notable synergistic interactions were further examined across a range of ratios using isobologram analysis. The toxicity of the individual samples and the combinations was assessed using the Artemia lethality assay (ALA) assay. Results: Apium graveolens seed extracts displayed notable antibacterial activity against the bacterial trigger of rheumatoid arthritis (P. mirabilis), but were ineffective against K. pneumoniae, A. baylyi, P. aeruginosa and S. pyogenes. The ethyl acetate extract was a particularly good inhibitor of P. mirabilis growth, with an MIC of 64µg/mL recorded. The hexane (MIC=256μg/mL) and methanolic extracts (MIC=750μg/mL) also displayed noteworthy inhibitory activity towards P. mirabilis. Furthermore, combining the extracts with conventional antibiotics resulted in significant potentiation of the inhibitory activity for
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La diarrhée infectieuse se distingue en trois grandes nosologies selon le germe qui la provoque: diarrhée bactérienne, la diarrhée virale, la diarrhée parasitaire. À celles-ci se rajoute une diarrhée plus ou moins chronique ou récidivante qui est celle de la diarrhée par surinfection d’un état de colopathie fonctionnelle.
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Celery preparations have been used extensively for several millennia as natural therapies for acute and chronic painful or inflammatory conditions . This chapter reviews some of the biological and chemical properties of various celery preparations that have been used as natural remedies. Many of these have varying activities and product qualities. A fully standardized celery preparation has been prepared known as an alcoholic extract of the seeds of a plant source derived from northern India . This is termed, Celery Seed Extract (CSE) and has been found to be at least as effective as aspirin, ibuprofen, and naproxen in suppressing arthritis in a model of polyarthritis . CSE can also reduce existing inflammation in rats. CSE has also been shown to provide analgesia in two model systems. CSE, in addition to acting as an analgesic and inflammatory agent, has been shown to protect against and/or reduce gastric irritation caused by NSAIDs, as well as act synergistically with them to reduce inflammation. The CSE was fractionated by organic solvent extractions, then subjected to column chromatography followed by HPLC and was characterized by mass spectrometry. This yielded a purified component that had specific inhibitory effects on Helicobacter pylori but was not active against Campylobacter jejuni or Escherichia coli. Additionally, toxicology studies did not reveal any clear signs of toxicity at doses relevant to human use. Also, unlike many dietary supplements, the available data suggest that CSE does not significantly affect the p450 enzyme systems and thus is less likely to alter the metabolism of drugs the individual may be taking. CSE may be a prototype of a natural product that can be used therapeutically to treat arthritis and other inflammatory diseases.
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The present study was aimed to study the antibacterial and antioxidant activity of different solvent extracts viz., Methanol, Diethyl ether and aqueous of Apium graveolens seeds. Uropathogens isolated from UTI samples, were tested against 10 different antibiotics that are commercially used for the treatment. The antibiotic resistant bacteria Escherichia coli and Pseudomonas aeruginosa isolated from Urinary Tract infected patients were used to determine the inhibitory potential of A.graveolens seed extract by using agar diffusion well method. From the analysis, methanol extract was showed highest inhibition, against bacterial pathogens when compared with other solvent extracts and standard antibiotics. The antioxidant activity of A.graveolens seed extracts was carried out 2, 2-Diphenyl-1- picrylhydrazyl (DPPH) assay method. Among the different extract tested Methanol extract was showed higher antioxidant activity than that of standard Gallic acid. Therefore, A.graveolens seed extract exhibiting enormous significance in therapeutic aspects and can applied for treating the UTI.
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Peptic ulcer is a disease of the Gastro-intestinal tract (GIT), which includes both gastric and duodenal ulcers. The occurrence of peptic ulcer disease has been attributed to the imbalance between aggressive factors like acid, pepsin, and Helicobacter infection on one hand and the local mucosa defenses like bicarbonate and mucus secretion and prostaglandins synthesis on the other hand. The most serious complications of peptic ulcer disease include hemorrhage, perforation, penetration, and gastric outlet obstruction. Ulcerative colitis is a form of inflammatory bowel disease (IBD). It is a form of colitis, a disease of the colon that includes characteristic ulcers, or open sores. IBD is often confused with irritable bowel syndrome. Ulcerative colitis is associated with a general inflammatory process that affects many parts of the body. Sometimes these associated extra-intestinal symptoms are the initial signs of the disease, such as painful arthritic knees in a teenager and may be seen in adults also. Several classes of pharmacological agents have proved to be effective in the management of the acid peptic disorders viz., antacids, acid suppressive agents, anticholinergic, cytoprotective agents, etc. A widespread search has been launched to identify new anti-ulcer therapies from natural sources to replace currently used drugs of doubtful efficacy and safety. Herbs, medicinal plants, spices, vegetables and crude drug substances are considered to be a potential source to control various diseases including gastric ulcer and ulcerative colitis. In the scientific literature, a large number of medicinal plants and their secondary metabolites with anti-ulcer potential have been reported. As the gastro protective effect can be linked to different mechanisms, once demonstrated the activity, the extracts and more appropriately the active compounds should be assessed for action mechanisms to elucidate their mode of action. Besides, new action mechanisms may be discovered.
Objective: To evaluate the efficacy of Chinese patent medicine wenweishu /yangweishu in the treatment of Helicobacter pylori (H. pylori) positive patients with chronic gastritis and peptic ulcer. Methods: A randomized, controlled and multicenter trial was conducted in 642 H. pylori positive patients with chronic gastritis or peptic ulcer. They were randomized to three groups: PCM group (n = 222, pantoprazole 40 mg twice a day, clarithromycin 500 mg twice a day, metronidazole 400 mg twice a day, for 7 days); PCM plus wenweishu group (n = 196); and PCM plus yangweishu group (n = 224). (14)C breath test was performed 4 weeks after therapy. For the patients with gastric ulcer, ulcer healing was determined by endoscopy after therapy. Results: Intention-to-treat H. pylori eradication rate for PCM group, PCM plus wenweishu group, and PCM plus yangweishu group were 57.2% (127/222), 62.2% (122/196), 60.3% (135/224), respectively (P = 0.295, 0.512). Per-protocol H. pylori eradication rates were 62.3% (127/204), 70.1% (122/174), 65.2% (135/207), respectively (P = 0.108, 0.532).Per-protocol analysis gastric ulcer healing rate were 61.9% (13/21) 100.0% (18/18), 86.4% (19/22) respectively. The healing rate in PCM plus wenweishu groups was statistically significantly higher than the rate in PCM group (P = 0.004). The rates of symptom relief in PCM plus wenweishu groups and PCM plus yangweishu were statistically significantly higher than the rate in PCM group (both P < 0.01). Side-effects were rare and comparable between groups. Conclusion: Although PCM combined with wenweishu or yangweishu in the treatment of H. pylori positive patients with chronic gastritis and peptic ulcer can not reach a significantly higher eradication rate, it can increase the rates of both gastric ulcer healing and symptom relief.
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Oleoresin is a mixture of volatile and nonvolatile components available in whole extract of natural herb or spice. It principally comprises essential oils and resin. Lemongrass oleoresins come from the Cymbopogon species, which grow in the tropical and subtropical regions of the world. Oleoresin of lemongrass is a dark green-colored viscous liquid having a characteristic lemon aroma and flavor and is mostly used as a flavoring ingredient. The lemon prefix in the lemongrass specifies the characteristic lemon-like odor, which is due to the availability of citral content (mixture of two isomeric aldehydes, geranial and neral). It has been utilized in synthesizing flavors, perfumes, cosmetics, detergents, and in the food and pharmaceutical industries. Different methods are used to extract the lemongrass essential oil, but steam distillation is the most suitable method as it doesn’t alter the quality of the obtained oil. The chemical composition of lemongrass oil varies depending on its extraction methods, genetic differences, harvest period, photoperiod, plant age, farming practices, and geographical origin. Lemongrass essential oil has shown several biological activities, including antimicrobial, antifungal, antiprotozoan, antioxidant, antidiarrheal, antimutagenic, antiinflammatory, antimalarial, antinociceptive, antihepatotoxic activities, etc. Lemongrass oil is a potent food preservative because of its extraordinary antifungal and antibacterial activities.
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With the increase in life expectancy, the prevalence of chronic diseases of the digestive tract, such as peptic ulcers and inflammatory bowel disease, and the metabolic syndrome associated with the current obesity epidemic have increased in the population. High cost and adverse reactions have led to the search for herbal medicines. However, the market is more demanding, and it is necessary to look for safer and more effective alternatives that can prevent and cure these diseases. The two projects carried out by Prof. Wagner Vilegas’ group (“Sustainable Use of Brazilian Biodiversity: Pharmacological and Chemical Prospection on Higher Plants” and “Standardized Extracts for the Treatment of Chronic Diseases”), led to an extensive chemical and pharmacological screening of Brazilian plants with ethnopharmacological indications for the treatment of cancer, ulcers, inflammation, diarrhea too. The first project aimed to investigate plant extracts more thoroughly under the chemical and pharmacological basis, whereas the second project was designed in order to standardize the method of preparationof the extracts, to evaluate the and qualitative and quantitative chemical composition of the extracts according to pharmacopoeial standards, as well as to deeply investigate the mechanistic basis of the biological activities observed. Several alkaloids, flavonoids, terpenoids, saponins, fatty acids, catechins, tannins and phenolic compounds were isolated, identified and/or detected. Pharmacological studies have indicated that some of these medicinal species, commonly used by the population, have proven efficacy for various disorders, with promising results. Therefore, next steps intend the production of pharmaceutical formulations that must have effectiveness and safety of use, which will also facilitate the access to the population to these phytopreparations.
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Helicobacter pylori (H. pylori), which is found in the stomach of approximately 50% of humans, remains there for almost the entire lifetime of the infected individual, leading to various gastrointestinal tract-associated disorders following full-blown infection. Due to the emergence of antibiotic resistance, recurrence and high cost of therapy, most antibiotic-based treatment strategies are not very effective in eradicating H. pylori infections. The quest for an alternative treatment free of these inconveniences is currently in demand. One of the important alternatives is propolis, produced by the honeybee Apis mellifera, which has been used to treat different diseases since it possesses a wide range of biochemical properties. Propolis has been reported as a useful therapeutic regimen against H. pylori, which is an important cause of gastric inflammation, peptic ulcer, gastric cancer, and lymphomas of mucosa-associated lymphoid tissues. Apart from propolis, various active compounds of other natural products have also been confirmed to be effective. This review compiles the scientific evidence of the role of propolis and other natural products against H. pylori-associated gastrointestinal tract-related health complexities by acing as an anti-angiogenic, anti-inflammatory, and antioxidant factor as well as via modulation of enzymatic activities. © 2017 Faculty of Health and Social Sciences, University of South Bohemia in Ceske Budejovice.
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In this era of increased concern on safety of chemical food additives, natural methods of preservation and natural preservatives are receiving increased attention. Despite their demonstrated potential use in food as preservatives, spices still remain primarily as food condiments. A lot of research has been done in the effort to demonstrate the antimicrobial potency of spices in cultured media. Though spices are less effective in foods than in cultured media, it is the use in foods that is of practical importance. This has not been exploited vis-a-vis the chemical additives. The antioxidant components of spices have been investigated but with minimal commercial utilization. Spices mostly used as antimicrobials and antioxidants do not exhibit toxicity at levels consumed. These are therefore evidently a group of plants, which have not fully been utilized in food technology. This review discusses and evaluates the antimicrobial and antioxidant potency of spices and advocates for more research and commercial utilization in foods. Br> Key words: Spices, chemical additives, anti-microbials, antioxidants J Food Tech in Africa (2002) 7, 39-44
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The starvation-survival response of Staphylococcus aureus as a result of glucose, amino acid, phosphate, or multiple-nutrient limitation was investigated. Glucose and multiple-nutrient limitation resulted in the loss of viability of about 99 to 99.9% of the population within 2 days. The remaining surviving cells developed increased survival potential, remaining viable for months. Amino acid or phosphate limitation did not lead to the development of a stable starvation-survival state, and cells became nonculturable within 7 days. For multiple-nutrient limitation, the development of the starvation-survival state was cell density dependent. Starvation survival was associated with a decrease in cell size and increase in resistance to acid shock and oxidative stress. There was no evidence for the formation of a viable but nonculturable state during starvation as demonstrated by flow cytometry. Long-term survival of cells was dependent on cell wall and protein biosynthesis. Analysis of [35S]methionine incorporation and labelled proteins demonstrated that differential protein synthesis occurred deep into starvation.
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The galactose oxidase-sodium borohydride method was used to specifically label the terminal N-acetylgalactosamine of three glycosphingolipids, Gm2-ganglioside, asialo-Gm2-ganglioside, and globoside. All of the compounds showed a minimum of 95% radiopurity, and generally more than 90% of the total radioactivity was located in the terminal galactosamine moiety. Globoside and asialo-Gm2-ganglioside were labeled to high specific activities comparable with those of the sphingolipids with a terminal galactose moiety, labeled with the same procedure. These labeled compounds were well suited as substrates for the study of specific sphingolipid N-acetylgalactosaminidase. Gm2-ganglioside, however, was a poor substrate for galactose oxidase, and its specific activity was only a small percentage of the others. Furthermore, because of the low specific activity of the galactosamine moiety, it was necessary to pretreat Gm2-ganglioside with unlabeled sodium borohydride to reduce the nonspecific labeling of other portions of the molecule. The use of labeled sodium borohydride of a very high specific activity may yield specifically labeled Gm2-ganglioside suitable for metabolic studies. Thus, the method is useful for labeling not only terminal galactose but also terminal N-acetylgalactosamine of glycosphingolipids.
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Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.
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Helicobacter pylori can transform from its normal helical bacillary morphology to a coccoid morphology. Since this coccoid form cannot be cultured in vitro, it has been speculated that it is a dormant form potentially involved in the transmission of H. pylori and in a patient's relapse after antibiotic therapy. In this study we determined the effects of aging, temperature, aerobiosis, starvation, and antibiotics on the morphologic conversion rate and culturability of H. pylori. Aerobiosis and the addition of a bactericidal antibiotic to the culture medium resulted in the highest conversion rate. During the conversion to coccoid forms, the cultures always lost culturability at the stage where 50% of the organisms were still in bacillary form; this result indicated that culturability and coccoid morphology are two separate but related entities. Independent of the conditions used to induce the conversion into coccoids, the morphological conversion was accompanied by several marked antigenic and ultrastructural changes. Also, both the total amounts and the integrity of RNA and DNA were significantly reduced in coccoid forms. With the potential-sensitive probe diOC(5)-3, a clear loss of membrane potential in coccoid forms was observed. Inhibition of protein or RNA synthesis by the addition of bacteriostatic antibiotics did not prevent the conversion to coccoid forms but resulted in an increased conversion rate. Hence, we conclude that conversion of H. pylori from the bacillary to the coccoid form is a passive process that does not require protein synthesis. Our data suggest that the coccoid form of H. pylori is the morphologic manifestation of bacterial cell death.
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A unique Helicobacter species, MZ640285, was isolated from a patient with X-linked hypogammaglobulinemia suffering from recurrent abdominal abscesses and was identified by 16S rRNA gene sequence analysis. In the phylogenetic tree, the isolate fell into a cluster which included Flexispira rappini, Helicobacter bilis, and Helicobacter sp. strain Mainz. Helicobacters are being increasingly recognized as pathogens in immunocompromised hosts. These fastidious bacteria are not easily cultured in the routine diagnostic laboratory, and this is the first report of their identification by 16S rRNA gene sequencing performed directly from a clinical specimen.
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Superoxide dismutase (SOD) is a nearly ubiquitous enzyme among organisms that are exposed to oxic environments. The single SOD ofHelicobacter pylori, encoded by the sodB gene, has been suspected to be a virulence factor for this pathogenic microaerophile, but mutations in this gene have not been reported previously. We have isolated mutants with interruptions in thesodB gene and have characterized them with respect to their response to oxidative stress and ability to colonize the mouse stomach. The sodB mutants are devoid of SOD activity, based on activity staining in nondenaturing gels and quantitative assays of cell extracts. Though wild-type H. pylori is microaerophilic, the mutants are even more sensitive to O2 for both growth and viability. While the wild-type strain is routinely grown at 12% O2, growth of the mutant strains is severely inhibited at above 5 to 6% O2. The effect of O2 on viability was determined by subjecting nongrowing cells to atmospheric levels of O2 and plating for survivors at 2-h time intervals. Wild-type cell viability dropped by about 1 order of magnitude after 6 h, while viability of the sodBmutant decreased by more than 6 orders of magnitude at the same time point. The mutants are also more sensitive to H2O2, and this sensitivity is exacerbated by increased O2 concentrations. Since oxidative stress has been correlated with DNA damage, the frequency of spontaneous mutation to rifampin resistance was studied. The frequency of mutagenesis of ansodB mutant strain is about 15-fold greater than that of the wild-type strain. In the mouse colonization model, only 1 out of 23 mice inoculated with an SOD-deficient mutant of a mouse-adapted strain became H. pylori positive, while 15 out of 17 mice inoculated with the wild-type strain were shown to harbor the organism. Therefore, SOD is a virulence factor which affects the ability of this organism to colonize the mouse stomach and is important for the growth and survival of H. pylori under conditions of oxidative stress.
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Resistance of Helicobacter pylori to clarithromycin has been associated with A2142G and A2143G point mutations in the 23S rRNA gene. Thus, the purpose of the present study was to determine the prevalence of each mutation in 52 clarithromycin-resistant H. pylori strains and to characterize the influence each type of mutation on the MIC. The MIC for clarithromycin was determined by the agar dilution method, and the point mutations of H. pylori were detected by PCR followed by restriction fragment length polymorphism. Clarithromycin MICs ranged from 2 to >256 microgram ml-1 among the 52 strains included in this study. Both the A2142G and the A2143G mutations were present in 94.2% of clarithromycin-resistant H. pylori strains examined. A relationship was observed between the presence of the A2142G mutation and the highest MIC values (p = 0.01). In an H. pylori-infected population, the A2142G mutation may incur to a greater probability of treatment failure if clarithromycin is used.
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A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
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Three new ligustilide derivatives (3-5) were isolated from the crude drug toki, the dried roots of the Umbelliferae plant Angelica acutiloba, together with a known ligustilide dimer, levistolide A (2), and four known oxygenated ligustilide derivatives, senkyunolide E (6), senkyunolide F (7), senkyunolide H (8) and senkyunolide I (9). Compound 3 was shown to be the angeloyl ester of 7. Compounds 4 and 5, designated tokinolide A and tokinolide B, are dimeric ligustilide derivatives with Diels-Alder-type (5) and cyclobutane-type (4) cyclization systems, respectively. The occurrence of compounds 2 to 9 in a fresh A. acutiloba sample was confirmed.
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Bioassay-directed isolation and purification of the hexane extract of Apium graveolens L. seeds led to the characterization of three compounds: beta-selinene (1), 3-n-butyl-4,5-dihydrophthalide (2) and 5-allyl-2-methoxyphenol (3). The structures of these compounds were established by using H-1 and C-13 NMR spectral methods. Compounds, 1-3 demonstrated 100% mortality on fourth-instar Aedes aegyptii larvae at 50, 25, and 200 mu g mL(-1), respectively, in 24 h. Also, 2 inhibited the growth of Candida albicans and Candida kruseii at 100 mu g mL(-1). It inhibited both topoisomerase-I and -II enzyme activities at 100 mu g mL(-1). Compound 2 displayed 100% mortality at 12.5 and 50 mu g mL(-1), respectively, when tested on nematodes Panagrellus rediuivus and Caenorhabditis elegans. The triglyceride 1,3-di[(cis)-9-octadecenoyl]-2-[(cis,cis)-9,12-octadecadienoyl]glycerol (4) and 3 were isolated for the first time from A. graveolens seeds, although 4 was not biologically active.
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Helicobacter pylori is a spiral, slow growing gram-negative microaerophilic bacterium. It has been shown to be the etiological agent of gastroduodenal diseases, such as chronic gastritis, gastric and duodenal ulcers, and gastric cancer. To address the influence of oxidative stress and its underlying mechanisms, we have compared proliferation, urease activity and protein expression profile of H. pylori incubated under normal microaerophilic (5% O2) and aerobic stress (20% O2) conditions. Oxidative-stress cells displayed coccoid morphology and time-dependent decrease in proliferation. The urease activity was completely abrogated after 32 h. We have further compared the protein expression profiles of H. pylori under normal growing and oxidative-stress conditions by a global proteomic analysis, which includes high-resolution 2-DE followed by MALDI-TOF-MS and bioinformatic databases search/peptide-mass comparison. The results revealed that more than ten proteins were differentially expressed under oxidative stress. Most notably, the protein expression levels of urease accessory protein E (UreE, an essential metallochaperone for urease activity) and alkylhydroperoxide reductase (AhpC) with antioxidant potential are greatly decreased under stress conditions. Measurements of messenger RNA transcription level by performing RT-PCR on total mRNA also confirmed that gene expressions for these two proteins are consistently repressed under oxygen tension. These changes form a firm basis to account for the loss of urease activity and anti-oxidative ability of H. pylori after long-term exposure to reactive oxygen. Conceivably, UreE and AhpC may thus be listed as potential targets for the development of therapeutic drugs against H. pylori.
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Z-Ligustilide (1), riligustilide (2), Z-6.6′,7.3a′-diligustilide (7), isovanillin and 4-hydroxy-3-methoxycinnamic acid, were isolated from the roots of Ligusticum porteri C. & R. (family Umbelliferae; common name: chuchupate), which are used in traditional medicine. The chemical characterization of 3,8-dihydro derivative of 7 (9), allowed the structural reassignment of a constituent previously isolated from L. wallichii.
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The United States Patent and Trademark Office webpage was searched for recent applications related to analgesia. The search identified 475 applications filed since March 15, 2001 containing the word “pain” in the title. In this first part of a multipart series examining trends in analgesic research and application, the list is presented. Future articles in the series will present individual applications.
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The structure and stereochemistry of angeolide (1), a novel dimeric lactone isolated from Angelica glauca Edgew., have been determined by X-ray analysis. Angeolide has been found to be the dimer of the butylidenephthalide 2 (ligustilide). The two isomeric ligustilides have been isolated from this plant and their stereochemistry has been determined. The relationship between angeolide (1) and ligustilide has been confirmed by chemical transformation. Angeolid, ein neues Lacton aus Angelica glauca Die Struktur und Stereochemie von Angeolid (1), einem neuen dimeren Lacton aus Angelica glauca Edgew. wurde mittels Röntgenstrukturanalyse aufgeklärt. Angeolid stellte sich als das Dimere von Butylidenphthalid 2 (Ligustilid) heraus. Die beiden isomeren Ligustilide wurden aus der oben genannten Pflanze gewonnen und ihre Stereochemie wurde aufgeklärt. Die Verwandtschaft von Angeolid (1) und Ligustilid wurde auf chemischem Wege nachgewiesen.
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Previous studies showed that some anti-inflammatory celery seed extracts (CSEs) were not gastrotoxic, in contrast to many OTC NSAIDs, when dosed to arthritic rats. The present investigation was designed to quantify the potential activity of CSEs against NSAID injury in rats with severe acute or chronic inflammation and to define the possible relationship of this to effects on mucosal prostaglandin production. Oral doses of alcoholic (A-CSE) (150-300 mg/kg) and supercritical fluid (S-CSE)(20-50 mg/kg) extracts of seeds of wild celery Apium graveolens from north India (Beagle Int. Nerang, Qld.) profoundly suppressed gastric injury elicited in disease-stressed female rats (Wistar, DA) with (a) chronic arthritic inflammation or (b) severe acute inflammation (from oleyl alcohol, 0.1 ml in tail base), fasted overnight and then dosed either (i) orally with ibuprofen (50 mg/kg), sodium naproxen (27.5 mg/kg), ketoprofen (5 mg/kg) or acidic ethanol (150 mg/kg); or (ii) parenterally with piroxicam (5 mg/kg) or nabumetone (100 mg/kg). By contrast several conventional gastroprotectants, e.g. sucralfate, cimetidine, bismuth salts, all given orally were ineffective in preventing gastric injury from parenteral piroxicam. Gastroprotection by CSEs was not over-ridden by co-dosing with isotonic HCl. Most other celery seed ''oils'' were ineffective in these assays. A-CSE was found to have marked inhibitory effects on PGE2 production by porcine gastric (fundic) mucosal explants in organ culture. Quercetin and mycrecetin which are reported components of some CSEs also inhibited PGE2 production in concentrations of 10 M, whereas limonene, another reported component of CSEs had little effect at the same concentration. These results suggest that gastroprotective effects of CSEs are probably mediated through non-prostaglandin mechanisms.
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The aroma volatiles of a local variety of celery from Libya were analysed using routine procedures. Nine of the identified components have not previously been reported as celery volatiles. Unusually, three constituents alone made up ca 70% of the total volatiles, 4,7-dimethoxy-5-(prop-2-enyl)benzo-1,3-dioxolan or apiole (ca 23%), 3-butylphthalide (ca 22%) and 3-butyltetrahydrophthalide or sedanolide (ca 24%). The latter two compounds are known to possess strong characteristic celery aroma. Some of the relatively uncommon celery volatiles, including three newly identified, have also been detected in parsley leaves and may, therefore, be characteristic to some extent of the Umbelliferae.
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A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
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Until recently, broth cultivation techniques for Campylobacter pylori were unavailable. We developed a method to cultivate bacterial cells within 24 h in liquid media. Cultivation in broth depended on the adequate dispersion of appropriate gases. A static broth at 37 degrees C in a GasPak jar (BBL Microbiology Systems, Cockeysville, Md.) with a CampyPak (BBL) envelope did not support growth after 5 days of incubation. A broth placed in a flask on a Gyrotory water bath shaker (150 rpm; New Brunswick Scientific Co., Inc., Edison, N.J.) fitted with a gassing hood connected to a gas mixture of 10% CO2, 5% O2, and 85% N2 supported good growth. An initial inoculum of 10(5), 10(3) to 10(4), or 10(2) CFU/ml resulted in greater than or equal to 10(8) CFU/ml after incubation for 24, 48, or 72 h, respectively. Under these conditions, the bacteria grew as motile, spiral bacilli rather than the oval and coccal bacilli occasionally reported. Several bases supported good growth when supplemented with serum. For the determination of basal growth conditions, brucella broth base was used. Fetal calf serum (1%) provided maximum growth. Vitox was not necessary for growth and did not augment growth. C. pylori grew over a wide optimal pH range of 5.5 to 8.5.
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Biopsy specimens were taken from intact areas of antral mucosa in 100 consecutive consenting patients presenting for gastroscopy. Spiral or curved bacilli were demonstrated in specimens from 58 patients. Bacilli cultured from 11 of these biopsies were gram-negative, flagellate, and microaerophilic and appeared to be a new species related to the genus Campylobacter. The bacteria were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer and thus may be an important factor in the aetiology of these diseases.
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The ability of flow cytometry to detect and enumerate viable bacteria during survival in a lakewater microcosm was assessed using Staphylococcus aureus as a model organism. Counts of colony-forming units (c.f.u.) on nutrient agar were not significantly different from those obtained by flow cytometric detection of rhodamine 123 stained bacteria and there was no evidence for a viable but nonculturable state using these methods. However c.f.u. were significantly lower when estimated using mannitol salts agar compared with nutrient agar. S. aureus was also enumerated immunofluorescently after staining with FITC-IgG. There was no significant difference between the population estimated immunofluorescently and by acridine orange direct counting, and unlike estimations of viability, only slight reductions in total cell numbers were observed. Changes in the protein and nucleic acid content of S. aureus during survival were also measured by flow cytometry to investigate any potential heterogeneity arising within the starved population. Flow cytometric determinations were found to correlate significantly with their respective chemical determinations. These results demonstrate the ability of flow cytometry to detect viable bacteria during starvation and to study changes in macromolecular content. They also illustrate the importance of using appropriate methods for the detection of viable bacteria in environmental samples.
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Various dyes were assessed for their ability to discriminate between viable and non-viable bacteria. Two methods of killing were employed: by heat treatment or by gramicidin treatment. Staining was carried out in two ways; by staining directly in the medium or by washing cells prior to staining in buffer. Carbocyanine and rhodamine 123 dyes only exhibited small changes in fluorescence between viable and non-viable populations of bacteria. Both oxonol dye (bis 1,3-dibutylbarbituric acid trimethine oxonol) and calcafluor white proved much more useful.
Article
Lipid A constitutes the outer monolayer of the outer membrane of Gram-negative bacteria and is essential for bacterial growth. Synthetic antibacterials were identified that inhibit the second enzyme (a unique deacetylase) of lipid A biosynthesis. The inhibitors are chiral hydroxamic acids bearing certain hydrophobic aromatic moieties. They may bind to a metal in the active site of the deacetylase. The most potent analog (with an inhibition constant of about 50 nM) displayed a minimal inhibitory concentration of about 1 microgram per milliliter against Escherichia coli, caused three logs of bacterial killing in 4 hours, and cured mice infected with a lethal intraperitoneal dose of E. coli.
Article
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Article
Two membrane potential sensitive dyes (Rhodamine 123 and bis-oxonol) and three nucleic acid dyes (propidium iodide, SYTO-13, and SYTO-17) were used to assess the effect of surfactants on Escherichia coli. The ability of E. coli to be stained by these probes was validated at different physiological states. Propidium iodide was used to assess the integrity of cell envelopes. Two double staining methods based on propidium iodide with SYTO-13 and bis-oxonol with SYTO-17 were used to improve the discrimination between bacteria and micelles or aggregated particles generated by the presence of surfactants. A rapid (1 h contact time between cells and surfactants, and less than 5 min for staining and obtaining data) Rhodamine 123 flow cytometric assay was developed to assess the bactericidal effect of surfactants.
Article
Seven new phthalide compounds with anti-Helicobacter pylori activities were isolated from the basidiomycete Phanerochaete velutina CL6387. The two most potent phthalide compounds, CJ-12,954 and CJ-13,014, have MICs of 5 ng/ml. The structure-activity relationship shows that the presence of a spiroketal part in addition to the phthalide part, greatly enhances the activity. The phthalide compounds appear to be specific for H. pylori, since they did not show antibacterial activities when tested against a panel of other microorganisms.
Article
Adherence may be an important virulence factor for Helicobacter pylori. Current methods available for quantitation of adherence are time consuming and liable to observer error. A new direct technique for fluorescent labelling of bacteria has been developed to quantitate adherence of H. pylori to epithelial cells by fluorescence activated cell sorting (FACS). Type strains of H. pylori, H. mustelae, H. cinaedi and H. fennelliae were grown microaerobically in broth culture for 24 h and fluorescently labelled by incubation with carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) at 37 degrees C. After washing to remove excess CFDA-SE, bacteria were co-incubated (ratio 10:1) with gastric epithelial cells at 37 degrees C for up to 24 h. After washing to remove non-adherent bacteria, epithelial cells were detached with EDTA (2 mM) and fixed with formaldehyde for flow cytometry. Adherence was quantitated both in terms of the proportion of cells with adherent H. pylori and as the mean number of adherent bacteria per cell. All H. pylori strains adhered to gastric-type epithelial cells. The proportion of cells with bound bacteria varied from 40-99% and the number of bacteria per cell from 1-50, both of which correlated with microscopy (r = 0.6, and r = 0.8 respectively, n = 35). Time course studies demonstrated saturation of binding by H. pylori within 90 min. For H. mustelae, H. cinaedi and H. fennelliae the proportion of cells with bound bacteria varied from 5-15% and the mean number of bacteria per cell was < 4. Binding of H. pylori to epithelial cells could be partly blocked by pre-incubation with polyclonal anti-sera or using oligosaccharides against potential binding epitopes of gastric mucus. Fluorescent labelling of H. pylori with CFDA-SE in combination with flow cytometry provides a quick, specific, and sensitive method to quantitate in vitro the adherence of H. pylori.
Article
This study investigated the growth of Helicobacter (H.) pylori in Brucella broth supplemented with either IsoVitaleX (1% vol/vol), hemin (.01% wt.vol), agar (0.3% wt/vol), or blood agar blocks (1.5% wt/vol agar). IsoVitaleX was found to significantly shorten the lag phase, while hemin inhibited the growth within the first 24 hours but later acted as a growth stimulant. There was a tendency toward stronger growth when blood agar blocks were added to the medium. Subsequent electron microscopic evaluation revealed that cells of H. pylori were attached to blood agar block surfaces. In contrast, the supplementation of Brucella broth with agar did not significantly increase the cell density. When H. pylori was grown in the presence of IsoVitaleX, strongly stainable electron-dense bodies (140-200 nm) were seen in the cytoplasms. Incubation of cultures on rotary shakers at 10 rpm significantly enhanced growth. The addition of glycerol (15% vol/vol) or fetal bovine serum (15% vol/vol) showed good ultrastructural preservation of bacteria with undamaged cell walls and cytoplasmic membranes, and cytoplasms were ribosome-dense. Cell counts revealed that cultures stored in glycerol or fetal bovine serum had a significantly lower loss in viability when compared with cultures stored without cryopreservatives. Unprotected cells of H. pylori showed on electron micrographs, clumping, cell lysis, and flagellar damage. Finally, the survival rates of H. pylori after multiple thawing from storage at -80 degrees C were best in Brucella broth/glycerol, Brucella broth/fetal bovine serum, and Brucella broth without cryopreservative (in descending order).
Article
Helicobacter pylori lipopolysaccharides (LPS) express human oncofetal antigens Lewis X and Lewis Y. The synthesis of Lewis Y involves the actions of alpha (1,3) and alpha (1,2) fucosyltransferases (FucTs). Here, we report the molecular cloning and characterization of genes encoding H. pylori alpha (1,2) FucT (Hp fucT2) from various H. pylori strains. We constructed Hp fucT2 knock-out mutants and demonstrated the loss of Lewis Y production in these mutants by enzyme-linked immunosorbent assay (ELISA) and immunoelectron microscopy. The Hp fucT2 gene contains a hypermutable sequence [poly (C) and TAA repeats], which provides a possibility of frequent shifting into and out of coding frame by a polymerase slippage mechanism. Thus, the Hp fucT2 gene displays two major genotypes, consisting of either a single full-length open reading frame (ORF; as in the strain UA802) or truncated ORFs (as in the strain 26695). In vitro expression of Hp fucT2 genes demonstrated that both types of the gene have the potential to produce the full-length protein. The production of the full-length protein by the 26695 fucT2 gene could be attributed to translational-1 frameshifting, as a perfect translation frameshift cassette resembling that of the Escherichia coli dnaX gene is present. Examination of the strain UA1174 revealed that its fucT2 gene has a frameshifted ORF at the DNA level, which cannot be compensated by translation frameshifting, accounting for its Lewis Y off phenotype. In another strain, UA1218, the fucT2 gene is apparently turned off because of the loss of its promoter. Based on these data, we proposed a model for the variable expression of Lewis Y by H. pylori, in which regulation at the level of replication slippage (mutation), transcription and translation of the fucT2 gene may all be involved.
Article
There have been a number of reports that natural foods such as garlic, honey, and capsaicin can inhibit Helicobacter pylori in vitro and each report has suggested the natural ingredient be used for treatment of the infection. We investigated whether garlic or capsaicin-containing peppers would actually inhibit H. pylori in vivo. We performed a prospective crossover study in healthy H. pylori-infected adults. We used the urea breath test to assess the status of the H. pylori infection. On separate days subjects received three test meals consisting of beef, tortillas, and salad with one of the following: fresh garlic (10 sliced cloves), capsaicin (six sliced fresh jalapeños), two tablets of bismuth subsalicylate (Pepto-Bismol, positive control), or nothing added (negative control). Breath testing was done before the first meal, the evening meal, and the following morning. At least 2 days elapsed between the test substances. Twelve subjects participated (seven men, five women), with an average age of 41.4 yr, range 27-51 yr. Ten subjects received garlic, six received jalapeños, and 11 received bismuth. Neither garlic nor capsaicin had any in vivo effect on H. pylori (median urease activity 28.5 vs 39.8 and 43.7 vs 46.6 before and after garlic and jalapeños, respectively) (p > 0.8). Bismuth had a marked inhibitory effect (median 55.8 vs 14.3 before and after bismuth) (p < 0.001), respectively. This study did not support a role for either garlic or jalapeños in the treatment of H. pylori infection. Caution must be used when attempting to extrapolate data from in vitro studies to the in vivo condition.
Article
Herbs have been used as food and for medicinal purposes for centuries. Research interest has focused on various herbs that possess hypolipidemic, antiplatelet, antitumor, or immune-stimulating properties that may be useful adjuncts in helping reduce the risk of cardiovascular disease and cancer. In different herbs, a wide variety of active phytochemicals, including the flavonoids, terpenoids, lignans, sulfides, polyphenolics, carotenoids, coumarins, saponins, plant sterols, curcumins, and phthalides have been identified. Several of these phytochemicals either inhibit nitrosation or the formation of DNA adducts or stimulate the activity of protective enzymes such as the Phase II enzyme glutathione transferase (EC 2.5.1.18). Research has centered around the biochemical activity of the Allium sp. and the Labiatae, Umbelliferae, and Zingiberaceae families, as well as flaxseed, licorice root, and green tea. Many of these herbs contain potent antioxidant compounds that provide significant protection against chronic diseases. These compounds may protect LDL cholesterol from oxidation, inhibit cyclooxygenase and lipoxygenase enzymes, inhibit lipid peroxidation, or have antiviral or antitumor activity. The volatile essential oils of commonly used culinary herbs, spices, and herbal teas inhibit mevalonate synthesis and thereby suppress cholesterol synthesis and tumor growth.
Article
Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm that the infection has been cured 4 to 6 weeks later. Antimicrobial resistance is largely responsible for treatment failures. Resistance to metronidazole can frequently be overcome by increasing the dose and duration of treatment with acid suppression. Clarithromycin is the most effective antibiotic against H. pylori but, unfortunately, resistance to it is increasing and can not be overcome by increasing the dose or duration of therapy with clarithromycin. The choice of therapy should be based on local susceptibility patterns. Re-treatment regimens for treatment failure should exclude antibiotics where acquired resistance is expected (i.e., clarithromycin and possibly metronidazole). Where available, treatment failure should prompt endoscopy and culture and susceptibility testing. Overall, higher doses and longer durations of treatment result in the best cure rates. When multiple treatment regimens fail, salvage therapy regimens such as bismuth or furazolidone quadruple therapy (a bismuth and tetracycline HCl 4 times a day along with a proton pump inhibitor twice a day, and either metronidazole 400 or 500 mg three times daily or furazolidone 100 mg three times daily for 14 days) can be used. Newer agents are needed to cope with the increasing prevalence of antibiotic resistance among H. pylori.
Article
Bioassay-directed isolation and purification of the hexane extract of Apium graveolens L. seeds led to the characterization of three compounds: beta-selinene (1), 3-n-butyl-4,5-dihydrophthalide (2) and 5-allyl-2-methoxyphenol (3). The structures of these compounds were established by using (1)H and (13)C NMR spectral methods. Compounds, 1-3 demonstrated 100% mortality on fourth-instar Aedes aegyptii larvae at 50, 25, and 200 microg mL(-)(1), respectively, in 24 h. Also, 2 inhibited the growth of Candida albicans and Candida kruseii at 100 microg mL(-)(1). It inhibited both topoisomerase-I and -II enzyme activities at 100 microg mL(-)(1). Compound 2 displayed 100% mortality at 12.5 and 50 microg mL(-)(1), respectively, when tested on nematodes, Panagrellus redivivus and Caenorhabditis elegans. The triglyceride, 1,3-di[(cis)-9-octadecenoyl]-2-[(cis,cis)-9, 12-octadecadienoyl]glycerol (4) and 3 were isolated for the first time from A. graveolens seeds, although 4 was not biologically active.
Article
To perform a meta-analysis of studies comparing twice daily, one-week triple therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A) (PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole (N) (PCN) for H. pylori eradication. Selection criteria: Comparative randomized trials of PCA vs. PCN were included. Data sources: PubMed database and abstracts from congresses until September 1999. Statistics: Meta-analysis was performed combining the Odds Ratios (OR) of the individual studies in a global OR (Peto method) both on an intention-to-treat (ITT) and on a per protocol (PP) basis. Twenty-two studies fulfilled the inclusion criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori eradication rates were 81% (95% CI: 79-83%) ITT, and 84% (82-86%) PP with PCA, and 81% (78-83%) ITT and 84% (82-86%) PP with PCN; the odds ratio for the effect of PCA vs. PCN was 1 (0.83-1.22) on an ITT, and 0.98 (0.8-1.2) on a PP basis. Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A was 81% (78-85%) ITT, vs. 86% (83-89%) with PC(250 b.d.)N. The odds ratio for this comparison was 0.68 (0.48-0.98). Finally, when comparing PC(500 b.d. )A against PC(250 b.d.)N ITT cure rates were 77% (74-80%), and 75% (72-78%) with an odds ratio of 1.18 (0.93-1.5). Overall, one-week combination regimens of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the PCN regimen obtains significantly better results when using low doses of C (250 mg b.d.).
Article
A bacterium is associated with a specific gastritis. Neutrophils infiltrate the necks of the glands, just deep to the infected foveolae. This infiltration rarely, if ever, occurs without H. pylori infection. Foveolar epithelial damage is common, with loss of cell structure. Electron microscopy suggests that the bacteria cause this damage as they attach to the superficial cell membrane. These features, defined by Whitehead et al as active changes, appear specific for H. pylori infection. The neutrophils and specific epithelial changes disappear within days of starting treatment for Helicobacter. They rapidly recur if the treatment is unsuccessful. Without treatment, the changes remain for decades and are severe in 10% to 20% of cases. Other changes occur in the mucosa. Reduced mucus secretion occurs in damaged or proliferating epithelium. This reduced secretion occurs near healing ulcers or with other types of inflammation but is often severe when Helicobacter is present. It returns to normal within weeks of treating the infection. The bacteria adhering to the cell membrane may cause this change directly. Lymphoid infiltration occurs with any type of chronic inflammation or immune reaction. The infiltration is not specific for Helicobacter, and it reduces slowly in months or years after eradication of H. pylori. Peptic ulceration, particularly duodenal ulceration, although not specific, is particularly common with H. pylori infection. The long-term inflammation probably causes other gastric pathology. Atrophy is common. Epithelial metaplasia occurs in about 20% of patients, usually mild. Other features, such as scarring, epithelial dysplasia, and in situ malignant change, are less common. They show little improvement after eradicating H. pylori. The part played by the bacteria in their cause remains uncertain. Pathologists see a long-standing chronic gastritis clearly related to a bacterium. The inflammation often is severe and commonly damages the mucosa, with ulceration, atrophy, metaplasia, and occasional premalignant changes. Physicians would treat inflammation of this degree in most other parts of the body. This disease is usually symptomless. There is some controversy, but eradicating Helicobacter often fails to improve nonulcer dyspepsia. This failure results in a continuing argument over whether or not to treat the infection. Meanwhile the pathology continues. A temporary solution to the problem is suggested: Patients infected with Helicobacter can give informed consent. Patients can be told about the infection, the pathology, the poor relationship to symptoms, and side effects of therapy, and they can decide.
Article
Up to 35% of patients infected with Helicobacter pylori fail to respond to standard anti-H. pylori therapy. With the rising prevalence antimicrobial resistance, the failure rates of conventional proton pump inhibitor-containing triple therapy are expected to increase. Pretreatment antibiotic resistance testing should be done whenever possible to allow for tailoring of the treatment regimens. The data on second-line or rescue therapy are limited and usually are subjected to various biases and confounding factors. Switching between clarithromycin and metronidazole should be considered if repeated courses of proton pump inhibitor-containing triple therapy are used as second-line therapy in the absence of antimicrobial sensitivity testing. The prolongation of therapy duration with proton pump inhibitor, amoxicillin, and clarithromycin is ineffective for clarithromycin-resistant strains. The bismuth-containing quadruple therapy is the best salvage treatment in the absence of pretreatment antibiotic susceptibility. Furazolidone quadruple therapy (where available) and rifabutin triple therapy are salvage therapies of last resort. If these regimens fail, culture and susceptibility testing is required.
Article
Helicobacter pylori is the cause of most peptic ulcer disease and a primary risk factor for gastric cancer. Eradication of the organism results in ulcer healing and reduces the risk of ulcer recurrence and complications. Testing and treatment have no clear value in patients with documented nonulcer dyspepsia; however, a test-and-treat strategy is recommended but for patients with undifferentiated dyspepsia who have not undergone endoscopy. In the office setting, initial serology testing is practical and affordable, with endoscopy reserved for use in patients with alarm symptoms for ulcer complications or cancer, or those who do not respond to treatment. Treatment involves 10- to 14-day multidrug regimens including antibiotics and acid suppressants, combined with education about avoidance of other ulcer-causing factors and the need for close follow-up. Follow-up testing (i.e., urea breath or stool antigen test) is recommended for patients who do not respond to therapy or those with a history of ulcer complications or cancer.
Article
An improved method of sample preparation was used in a microplate assay to evaluate the bactericidal activity levels of 96 essential oils and 23 oil compounds against Campylobacter jejuni, Escherichia coli O157:H7, Listeria monocytogenes, and Salmonella enterica obtained from food and clinical sources. Bactericidal activity (BA50) was defined as the percentage of the sample in the assay mixture that resulted in a 50% decrease in CFU relative to a buffer control. Twenty-seven oils and 12 compounds were active against all four species of bacteria. The oils that were most active against C. jejuni (with BA50 values ranging from 0.003 to 0.009) were marigold, ginger root, jasmine, patchouli, gardenia, cedarwood, carrot seed, celery seed, mugwort, spikenard, and orange bitter oils; those that were most active against E. coli (with BA50 values ranging from 0.046 to 0.14) were oregano, thyme, cinnamon, palmarosa, bay leaf, clove bud, lemon grass, and allspice oils; those that were most active against L monocytogenes (with BA50 values ranging from 0.057 to 0.092) were gardenia, cedarwood, bay leaf, clove bud, oregano, cinnamon, allspice, thyme, and patchouli oils; and those that were most active against S. enterica (with BA50 values ranging from 0.045 to 0.14) were thyme, oregano, cinnamon, clove bud, allspice, bay leaf, palmarosa, and marjoram oils. The oil compounds that were most active against C. jejuni (with BA50 values ranging from 0.003 to 0.034) were cinnamaldehyde, estragole, carvacrol, benzaldehyde, citral, thymol, eugenol, perillaldehyde, carvone R, and geranyl acetate; those that were most active against E. coli (with BA50 values ranging from 0.057 to 0.28) were carvacrol, cinnamaldehyde, thymol, eugenol, salicylaldehyde, geraniol, isoeugenol, citral, perillaldehyde, and estragole; those that were most active against L monocytogenes (with BA50 values ranging from 0.019 to 0.43) were cinnamaldehyde, eugenol, thymol, carvacrol, citral, geraniol, perillaldehyde, carvone S, estragole, and salicylaldehyde; and those that were most active against S. enterica (with BA50 values ranging from 0.034 to 0.21) were thymol, cinnamaldehyde, carvacrol, eugenol, salicylaldehyde, geraniol, isoeugenol, terpineol, perillaldehyde, and estragole. The possible significance of these results with regard to food microbiology is discussed.
Article
Bacterial culture has played an irreplaceable role in the discovery and characterisation of Helicobacter pylori. The main topic of the present article is to critically review the role of culture in the management of H. pylori infection in clinical practice, from diagnosis to treatment. The available data suggest that H. pylori culture is an invasive, time-consuming method, offering quite low sensitivity, requiring significant cost for the patient, and which, in practice, tests very few antibiotics, with a questionable contribution to the management of non-responder patients. Therefore, whether patients should undergo (and pay for) an upper endoscopy for bacterial culture remains a debatable matter.
Article
From the water-soluble portion of the methanol extract of celery seed (fruit of Apium graveolens L.) five sesquiterpenoid glucosides (celerioside A-E) and three phthalide glycosides (celephtalide A-C) were isolated together with six aromatic compound glucosides, two norcarotenoid glucosides and a lignan glucoside. Their structures were determined by spectral investigations.
Article
Helicobacter infection is the single most common cause of gastric cancer worldwide. Although infection prevention and eradication of established infection offer the potential for cure, these strategies are neither feasible nor practical for widespread implementation. Patients most at risk need to be identified and targeted for treatment. For disease to occur, bacterial, environmental, and nutritional factors require a genetically susceptible host. Consequently, it is important to understand how the organism interacts with the host to cause disease. Only through an understanding of what places a patient at risk can we hope to identify susceptible patients early enough in disease to have an impact on their outcome. The immune response is the single most important determinant of disease. Single nucleotide polymorphisms within the promoter region of several critical proinflammatory genes dramatically increase the risk of Helicobacter-associated gastric cancer. Additionally, environmental and dietary factors may modulate the immune response or directly influence key apoptotic and proliferative signaling cascades to alter disease presentation. Lastly, concurrent disease states may have a dramatic impact on the host response to Helicobacter infection and influence disease. An understanding of the immune signaling pathways responsible for disease and the ways in which environmental risk factors influence these pathways will allow identification of populations that are most at risk and targeted prevention and treatment strategies.
Article
Escherichia coli and Bacillus subtilis aconitases can act as iron and oxidative stress-responsive post-transcriptional regulators. Here, it is shown that a Salmonella enterica serovar Typhimurium LT2 acnB mutant exhibits impaired binding to the surface of J774 macrophage-like cells. Proteomic analyses were used to investigate further the binding defect of the acnB mutant. These revealed that the levels of the flagellum protein FliC were much lower for the acnB mutant. This strain was correspondingly less motile and possessed fewer flagella than either the parental strain or the acnA and acnAB mutants. The acnB lesion did not alter fliC transcription, nor did apo-AcnB select the fliC transcript from a library of S. enterica transcripts; thus, the effect of AcnB on FliC is indirect. Evidence is presented to show that apo-AcnB regulates FliC synthesis via interaction with the ftsH transcript to decrease the intracellular levels of FtsH. The lower levels of FtsH protease activity then influence sigma32, DnaK and, ultimately, FliC production.
Article
This study will explore a few recipes in relation to what monastic medicine considered kidney disorders. Technical terms, such as strangury, cause us difficulties in interpreting early medieval monastic medicine. The action described can vary considerably. For example, he has action for urination problems that center in the verb: (in translation) "dries out", "quietens", "expels", "moves", "provoking", and treating "retention of urine". Sometimes the term "diuretic" is used. The Lorsch monastic book of medical recipes, written around 800, employed the words "deuritica" and "diureticon" but most of monastic accounts simply say something similar to that in Reichenau Monastery's recipe book, 9th or 10th century: "urinam movet/moves the urine"; "urinam provocat/stimulates urination"; "ad difficultate urine/difficulty in urination". In order to examine the relationship between diagnosis and therapy, let us turn to a disease that is difficult even for modern medicine, diabetes. An examination of several early medieval monastic accounts reveals that they could have effectively treated diabetes.