RESUMEN
Gastritis is the acute or chronic inflammation of gastric mucosa and is triggered by diverse factors. Treatments used for non-bacterial gastritis include proton pump inhibitors, histamine H2 receptor inhibitors, and antacids, and their use is linked to various side effects. Research on alternative therapeutics using food or food-based products is extensive, mostly in preclinical research. We aimed at documenting the clinical advances in food-based therapies as alternative therapeutics for gastritis. Articles with information on the treatment of gastritis with food or food-based products published until December 1, 2020 were identified through a systematic search in PubMed Medline Database. Additionally, references of retrieved articles were screened for relevant reviews and meta-analyses. Two investigators independently selected and reviewed the titles and abstracts of articles and extracted the study characteristics (PICO framework) and key findings. Dual quality assessment and data extraction were performed. We found 28 clinical studies evaluating garlic, turmeric, red peppers, broccoli sprouts, cranberry juice, honey, oils, and probiotics contained in different foods, such as juices, yogurt, and cheese. The existing literature presents a high risk of bias, and results of the same should be evaluated and replicated with precaution; more rigorous clinical studies are lacking.
Asunto(s)
Queso , Gastritis , Humanos , Gastritis/tratamiento farmacológico , Gastritis/inducido químicamente , Inhibidores de la Bomba de Protones/uso terapéutico , Antiácidos/efectos adversos , Inflamación/tratamiento farmacológicoRESUMEN
Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.
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Antiulcerosos , Aguas Minerales , Úlcera Gástrica , Ratas , Animales , Indometacina/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/prevención & control , Ratas Wistar , Antiulcerosos/farmacología , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios/efectos adversos , Mucosa Gástrica , Agua de Mar , Inflamación/tratamiento farmacológicoRESUMEN
Licania rigida Benth., a Brazilian endemic plant, has been traditionally used for treating inflammation and stomach pain. This work investigates the anti-inflammatory and gastroprotective activities of the ethanolic extract from L. rigida seeds (EELr) by in vitro and in vivo methods. The phytochemical profile was determined and the in vitro antioxidant activity was investigated by radical scavenging and thiobarbituric acid reactive substances methods. The ovalbumin denaturation method was used with sodium diclofenac as standard for the in vitro anti-inflammatory activity assessment. Acetylsalicylic acid was used to induce gastric ulcers in male mice and then to evaluate the preventive and therapeutic gastroprotective effect of EELr, using omeprazole as the reference drug. The extract exhibited relevant amount of phenolic compounds and flavonoids, in particular, demonstrating in vitro antioxidant capacity. EELr was able to inhibit almost 60% of ovalbumin denaturation at a concentration considered low. It also prevented the decrease of biochemical markers for oxidative stress such as superoxide dismutase (SOD) and reduced glutathione (GSH) in the stomach and SOD and catalase (CAT) in the liver. EELr also significantly decreased the number of lesions as well as reduced the ulcerated area when used as therapy. The observed effect may be due to its phenolic compounds, such as chlorogenic acid, caffeic acid and tannins, as previously reported. EELr is a potential source of compounds with anti-inflammatory activity, protects the liver from oxidative damage and improves healing of aspirin-induced ulcers. This work contributes to the knowledge of L. rigida species.
Asunto(s)
Antiulcerosos , Chrysobalanaceae , Úlcera Gástrica , Ratas , Ratones , Animales , Extractos Vegetales/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Fitoterapia , Chrysobalanaceae/química , Ovalbúmina/farmacología , Ratas Wistar , Antiulcerosos/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Etanol/química , Aspirina/farmacología , Semillas , Superóxido Dismutasa , Mucosa GástricaRESUMEN
Bioactivity-guided fractionation of F. drupacea Thunb. extract revealed that the water fraction (FDWF) increased pH of the artificial gastric juice from 1.2 to 5.67 ± 0.015. The gastroprotective effect of FDWF against ulcer induced by ethanol was evaluated in rats. In ulcerogenic rats, increase in the gastric juice volume and ulcer lesions, and decrease in the gastric pH were evident. However, pretreatment with FDWF (100 mg/kg b.wt., p.o.) significantly inhibited lesion index, reduced gastric juice volume by 56.09% and increased gastric pH value. When given after ethanol, the same dose of FDWF led to significant healing of the gastric ulcer, with 75.60% reduction of gastric juice volume, and increase in pH value. In both prophylactic and therapeutic-treated groups, the level of superoxide dismutase and reduced glutathione in gastric homogenate were increased, while that of malondialdehyde was decreased. Also, the levels of succinate dehydrogenase and lactate dehydrogenase were increased, while that of acid phosphatase was decreased. In addition, the inflammatory markers; IL-10 and PGE2 were significantly increased. The histopathological results confirmed the above findings and indicated that the antiulcer effect of FDWF is mediated, at least in part, through antioxidant and anti-inflammatory mechanisms. Twenty-three compounds were tentatively identified in FDWF using UPLC-PDA-ESI-MS/MS and most of them were found to be phenolic acid derivatives. FDWF was standardized to contain 23.66 ± 2.62 mg/g and 8.86 ± 0.29 mg/g of quinic acid and chlorogenic acid, respectively. Accordingly, FDWF is a potential natural product that could increase the healing of gastric mucosal injury and prevents the development of ethanol-induced gastric mucosal injury in rats.
Asunto(s)
Antiulcerosos , Ficus , Ratas , Animales , Etanol/química , Extractos Vegetales/uso terapéutico , Úlcera/tratamiento farmacológico , Úlcera/patología , Espectrometría de Masas en Tándem , Antiulcerosos/farmacología , Mucosa GástricaRESUMEN
Enteric dysfunctions are common for various histamine-related intestinal disorders. Vegetal diamine oxidase (vDAO), an enzyme able to decompose histamine and thus alleviate histamine-related dysfunctions, was formulated in gastro-resistant tablet forms for oral administration as a food supplement and possible therapeutic agent. A major challenge for the use of proteins in the pharmaceutical field is their poor stability. In this study, vDAO was freeze-dried in the absence or in the presence of sucrose or trehalose as cryoprotectants and then formulated as tablets by direct compression. The stability of the obtained preparations was followed during storage at 4 °C and -20 °C for 18 months. In vitro dissolution tests with the vDAO powders formulated as tablets were performed in simulated gastric and in simulated intestinal fluids. The tablets obtained with the powder of the vDAO lyophilized with sucrose or trehalose cryoprotectants offered better protection for enzyme activity. Furthermore, the release of the vDAO lyophilized with the cryoprotectants was around 80% of the total loaded activity (enzyme units) compared to 20% for the control (vDAO powder prepared without cryoprotectants). This report revealed the potential of sucrose and trehalose as cryoprotectants to protect vDAO from freeze-drying stress and during storage, and also to markedly improve the vDAO release performance of tablets obtained with vDAO powders.
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Amina Oxidasa (conteniendo Cobre) , Trehalosa , Sacarosa , Histamina , Polvos , Crioprotectores/farmacología , Liofilización , Estabilidad de MedicamentosRESUMEN
PURPOSE: Gastrointestinal (GI) bleeding is one of the most common serious adverse drug events. Guidelines recommend proton pump inhibitor (PPI) gastroprotection to prevent upper GI bleeding in high-risk patients, but this practice is underused. METHODS: To explore prescribing practices and barriers to the use of PPI gastroprotection, including dynamics within and across specialties, we conducted semistructured interviews with physicians in 4 specialties at a single institution. We performed thematic analysis of barriers, organized around the theoretical domains framework. RESULTS: The sample included 5 primary care physicians (PCPs), 4 cardiologists, 3 gastroenterologists, and 3 vascular surgeons. Most PCPs, gastroenterologists, and vascular surgeons seldom prescribed PPI gastroprotection. Cardiologists varied most in their use of PPI gastroprotection, with some prescribing it consistently and others never. Major barriers related to the following 3 themes: (1) knowledge, (2) decision processes, and (3) professional role. Knowledge of guidelines was greatest among cardiologists and gastroenterologists and low among PCPs and vascular surgeons, and PCPs tended to focus on adverse effects associated with PPIs, which made them reluctant to prescribe them. For cardiologists, prevention of bleeding was usually a priority, but they sometimes deferred prescribing to others. For the other 3 specialties, PPI gastroprotection was a low priority. There was unclear delineation of responsibility for prescribing gastroprotection between specialties. CONCLUSIONS: Major barriers to PPI gastroprotection relate to knowledge, decision processes, and professional role, which operate differentially across specialties. Multicomponent interventions will likely be necessary to improve guideline-based use of PPIs to prevent upper GI bleeding.VISUAL ABSTRACT.
Asunto(s)
Hemorragia Gastrointestinal , Inhibidores de la Bomba de Protones , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/prevención & control , Humanos , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
Schinus molle is a plant traditionally used in Mexico to treat gastric disorders. However, no scientific evidence has been reported on its gastroprotective effect. The aim of the current contribution was to conduct a bioassay-guided study on S. molle to evaluate its gastroprotective activity in a model of Wistar rats given ethanol orally to induce gastric lesions. The hexane and dichloromethane extracts from the tested plant showed over 99% gastroprotection at a dose of 100 mg/kg. From the hexane extract, two of the three fractions (F1 and F2) afforded over 99% gastroprotection. The F1 fraction was subjected to column chromatography, which revealed a white solid. Based on the ESI-MS analysis, the two main compounds in this solid were identified. The predominant compound was probably a triterpene. This mixture of compounds furnished about 67% gastroprotection at a dose of 100 mg/kg. Pretreatment with L-NAME, indomethacin, and NEM was carried out to explore the possible involvement of nitric oxide, prostaglandins, and/or sulfhydryl groups, respectively, in the gastroprotective activity of the white solid. We found evidence for the participation of all three factors. No antisecretory activity was detected (tested by pylorus ligation). In conclusion, evidence is herein provided for the first time of the gastroprotective effect of S. molle.
Asunto(s)
Anacardiaceae , Antiulcerosos , Úlcera Gástrica , Ratas , Animales , Prostaglandinas/farmacología , Óxido Nítrico/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/patología , Antiulcerosos/química , Hexanos/farmacología , Ratas Wistar , Compuestos de Sulfhidrilo/farmacología , Extractos Vegetales/química , Mucosa GástricaRESUMEN
CONTEXT: The gastroprotective effect of Heliotropium indicum L. (Boraginaceae), a plant traditionally used in Mexico to treat gastric ulcers, has been previously reported. However, no active compound was identified. OBJECTIVE: The current contribution aimed to isolate, through a bioassay-guided study, at least one compound from H. indicum with considerable gastroprotective activity, examine its effect on ethanol-induced gastric lesions in mice, and explore possible mechanisms of action. MATERIALS AND METHODS: Three extracts (hexane, dichloromethane, and methanol) were obtained from H. indicum leaves. Their 30 and 100 mg/kg doses were assessed on ethanol-induced gastric lesions in male CD1 mice. Since the dichloromethane extract was the most active, successive chromatographies were carried out leading to the identification of the most active compound. This compound (at 3-100 mg/kg) was compared to carbenoxolone (at 10-100 mg/kg) in biological evaluations in mice. Pre-treatments with indomethacin (10 mg/kg, s.c.), L-NAME (70 mg/kg, i.p.), and NEM (10 mg/kg, s.c.) were performed independently to determine the participation of prostaglandins, nitric oxide, and/or sulfhydryl groups, respectively, in the mechanism of action of the compound. RESULTS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, a compound isolated from H. indicum, afforded dose-dependent gastroprotective activity. The maximum effect was observed at 100 mg/kg (90.13 ± 3.08%), with an ED50 of 5.92 ± 2.48 mg/kg. Gastroprotection was not modified by pre-treatment with indomethacin, L-NAME, or NEM. CONCLUSIONS: (E)-Ethyl-12-cyclohexyl-4,5-dihydroxydodec-2-enoate, isolated from H. indicum, was found to produce a substantial gastroprotective effect. Prostaglandins, nitric oxide, and non-protein sulfhydryl groups are not involved in its mechanism of action.
Asunto(s)
Antiulcerosos , Heliotropium , Animales , Antiulcerosos/farmacología , Antiulcerosos/uso terapéutico , Etanol , Indometacina/farmacología , Masculino , Cloruro de Metileno , Ratones , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico , Prostaglandinas , Ratas , Ratas Wistar , Compuestos de SulfhidriloRESUMEN
INTRODUCTION: Adiponectin is a hormone secreted by adipocytes, which exhibits insulin-sensitizing and anti-inflammatory properties and acts through adiponectin receptors: AdipoR1 and AdipoR2. The aim of the study was to evaluate whether activation of adiponectin receptors AdipoR1 and AdipoR2 with an orally active agonist AdipoRon has gastroprotective effect and to investigate the possible underlying mechanism. METHODS: We used two well-established mouse models of gastric ulcer (GU) induced by oral administration of EtOH (80% solution in water) or diclofenac (30 mg/kg, p.o.). Gastroprotective effect of AdipoRon (dose 5 and 50 mg /kg p.o) was compared to omeprazole (20 mg/kg p.o.) or 5% DMSO solution (control). Clinical parameters of gastroprotection were assessed using macroscopic (gastric lesion area) and microscopic (evaluation of the gastric mucosa damage) scoring. To establish the molecular mechanism, we measured: myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities; glutathione (GSH) level; and IL-1ß, adenosine monophosphate-activated protein kinase (AMPK), and phosphorylated AMPK expression in gastric tissue. RESULTS: AdipoRon produced a gastroprotective effect in both GU mouse models as evidenced by significantly lower macroscopic and microscopic damage scores. AdipoRon exhibited anti-inflammatory effect by reduction in MPO activity and IL-1ß expression in the gastric tissue. Moreover, AdipoRon induced antioxidative action, as demonstrated with higher GSH levels, and increased SOD and GPX activity. CONCLUSIONS: Activation of AdipoR1 and AdipoR2 using AdipoRon reduced gastric lesions and enhanced cell response to oxidative stress. Our data suggest that AdipoR1 and AdipoR2 activation may be an attractive therapeutic strategy to inhibit development of gastric ulcers.
Asunto(s)
Omeprazol/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Piperidinas/administración & dosificación , Receptores de Adiponectina/agonistas , Úlcera Gástrica/tratamiento farmacológico , Administración Oral , Animales , Catalasa/metabolismo , Diclofenaco/efectos adversos , Modelos Animales de Enfermedad , Etanol/efectos adversos , Masculino , Ratones , Omeprazol/farmacología , Peroxidasa/metabolismo , Piperidinas/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Superóxido Dismutasa/metabolismo , Resultado del TratamientoRESUMEN
Context: Vitis vinifera leaves are traditionally used in Tunisian folk medicine to treat digestive pathologies.Objective: We aimed to compare the gastroprotective effects of hydromethanolic leaves extracts of wild and cultivated grapes accessions native of Tunisia.Materials and methods: The phytochemical analysis of grapevine leaves extracts was performed. The gastroprotective activity was evaluated by ethanol-induced gastric-ulcer in rats pre-treated with increased doses of the extracts or with the standard omeprazole. Index of gastric secretions (volume, pH and gastric mucus production), stomach wall histology and biochemical parameters were estimated for assessment of anti-secretory and gastroprotective effects of the extracts.Results: Pre-treatment with grapevine leaves extracts decreased significantly gastric volume, gastric mucosal damage and increased significantly gastric juice pH compared with the negative control group. The extracts prevented ethanol-induced decrease of the activity of antioxidant enzymes while the levels of malondialdehyde and of reduced glutathione were decreased significantly. Moreover, the most marked effect was observed at low doses of wild ecotype 'Nefza-I' extracts.Conclusion: The leaves of Vitis species might be suitable as a functional food for therapeutic purpose and demonstrates gastroprotective action in gastric lesions model. Both accessions exhibited gastroprotective effects, but wild 'Nefza-I' ecotype was more effective than cultivar 'Marsaoui'.
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Antiulcerosos/farmacología , Antioxidantes/farmacología , Mucosa Gástrica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Hojas de la Planta , Úlcera Gástrica/prevención & control , Vitis , Animales , Antiulcerosos/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Modelos Animales de Enfermedad , Etanol , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Masculino , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Hojas de la Planta/crecimiento & desarrollo , Ratas Wistar , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patología , Túnez , Vitis/química , Vitis/crecimiento & desarrolloRESUMEN
Less than 2 centuries have elapsed since the identification of hydrochloric acid in the stomach. The clarification of the molecular mechanisms allowed the effective therapeutic suppression of gastric acid secretion. The spectacular advances in the treatment of acid-related disorders represent a synthesis of the contributions of several brilliant pharmacologists, basic scientists, and clinical physicians. Effective gastric acid suppressive therapy has dramatically improved the therapy and outcome of acid-related disorders. The introduction of proton pump inhibitors (PPIs) in clinical practice has significantly changed the medical management of upper gastrointestinal disorders. PPIs represent the "gold-standard" therapy in acid-related disorders. However, some challenges persist in the therapy of acid related diseases, including management of patients who respond inadequately to PPI therapy, more effective gastroprotection, or more powerful antisecretory treatment for the eradication of Helicobacter pylori infection. New antisecretory drugs are currently being developed and investigated to further provide a more effective and profound gastric acid secretion inhibition. The major advance has been the development of acid pump -antagonists, the potassium channel acid blocking drugs (-P-CABs). Long-term studies comparing P-CABs with PPIs will help to define the exact place and safety profile of this class of drug in the management of acid-related disorders.
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Ácido Gástrico/metabolismo , Fármacos Gastrointestinales/farmacología , Desarrollo de Medicamentos , Fármacos Gastrointestinales/uso terapéutico , Antagonistas de los Receptores Histamínicos/farmacología , Humanos , Bloqueadores de los Canales de Potasio/farmacología , Inhibidores de la Bomba de Protones/efectos adversos , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
CONTEXT: Alpinia officinarum Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases. OBJECTIVE: To investigate the potential protective mechanism of total flavonoids from the rhizomes of A. officinarum (F-AOH) in ethanol-induced acute gastric in vivo and in vitro. MATERIALS AND METHODS: In vivo: Gastric damage was induced in BALB/c mice by administering ethanol (10 mL/kg) after oral treatment with F-AOH at 126.8, 63.4 and 31.7 mg/kg or ranitidine (Ran) at 100 mg/kg (1 week of continuous gavage). In vitro: Gastric mucosal epithelial cells (GES-1) were incubated with F-AOH (8, 4 and 2 µg/mL) for 16 h and treated with 7% ethanol for 4 h. The extent of gastric damage was assessed histopathologically, and the expression of NF-κB, COX-2, TNF-α, iNOS and IL-1ß was quantified by Western blot analysis. In addition, proinflammatory mediators and concentrations of motilin (MTL) and gastrin (GAS) were measured by ELISA test. RESULTS: F-AOH effectively reduced the ulcer index (from 23.4 ± 4.28 to 8.32 ± 1.5) and reduced release of inflammatory mediators (IL-1ß, IL-6, TNF-α and PGE2), increased the content of nitric oxide and improved GAS and MTL secretion. The 50% inhibitory concentration (IC50) of F-AOH on cell damage was 17 µg/mL. F-AOH increased ethanol-induced cell survival (from 47 to 85%) and inhibited the expression of NF-κB, COX-2, TNF-α, IL-1ß and iNOS proteins. CONCLUSIONS: F-AOH inhibits ethanol-induced gastric mucosal damage, provides a theoretical basis for galangal in the treatment of other causes of GU, and promotes the application of galanga in the treatment of GU.
Asunto(s)
Alpinia/química , Antiulcerosos/farmacología , Flavonoides/farmacología , Úlcera Gástrica/prevención & control , Animales , Antiulcerosos/administración & dosificación , Antiulcerosos/aislamiento & purificación , Línea Celular , Relación Dosis-Respuesta a Droga , Etanol/toxicidad , Femenino , Flavonoides/administración & dosificación , Flavonoides/aislamiento & purificación , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Ranitidina/farmacología , RizomaRESUMEN
Gastric epithelial cells are important components of mucosal protection and targets of nonsteroidal anti-inflammatory drugs (NSAIDs)-induced injury. Diclofenac (DFN) is one of the most widely used NSAIDs; however, even its short-term use can induce gastric erosions and ulcers. Nerve growth factor (NGF) has been reported to act not only on neuronal cells but also on endothelial cells; however, its action on gastric epithelial cells is unknown. This study was aimed to determine, whether NGF can protect gastric epithelial cells against DFN-induced injury, and to determine the underlying molecular mechanisms with a focus on mitochondria, survivin, and insulin-like growth factor 1 (IGF-1). Cultured normal rat gastric mucosal epithelial cells 1 (RGM1) were treated with phosphate-buffered saline (PBS; control), NGF (100 ng/mL) and/or DFN (0.25-1.00 mM) for 4 hours. We examined: (1) cell injury by confocal microscopy; (2) cell death/survival using Calcein AM live cell tracking dye; (3) mitochondrial structure and membrane potential function using MitoTracker in live cells; and (4) expression of NGF, its receptor - tropomyosin receptor kinase A (TrkA), survivin and IGF-1 by immunostaining. DFN treatment of RGM1 cells for 4 hours caused extensive cell injury, mitochondrial disintegration, reduced cell viability (from 94 ± 3% in controls to 14 ± 4% in 0.5 mM DFN-treated cells; P < 0.001), and expression of survivin and IGF-1. NGF treatment significantly increased survivin and IGF-1 expression by 41% and 75%, respectively versus PBS controls. Pretreatment with NGF before DFN treatment reduced mitochondrial damage and cell death by 73% and 82%, respectively versus treatment with DFN alone (all P < 0.001). This study also showed the presence of high-affinity TrkA receptors in the plasma membrane and mitochondria of RGM1 cells indicating novel actions of NGF.
RESUMEN
PURPOSE OF REVIEW: The gastroduodenal mucosal layer is a complex and dynamic system that functions in an interdependent manner to resist injury. We review and summarize the most updated knowledge about gastroduodenal defense mechanisms and specifically address (a) the mucous barrier, (b) membrane and cellular properties, and vascular, hormonal, and (c) gaseous mediators. RECENT FINDINGS: Trefoil factor family peptides play a crucial role in cellular restitution by increasing cellular permeability and expression of aquaporin channels, aiding cellular migration and tissue repair. Additionally, evidence suggests that the symptoms of functional dyspepsia may be attributed to alterations in the duodenum, including low-grade inflammation and increased mucosal permeability. The interaction of the various mucosal protective components helps maintain structural and functional homeostasis. There is increasing evidence suggesting that the upper GI microbiota plays a crucial role in the defense mechanisms. However, this warrants further investigation.
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Duodeno/fisiología , Mucosa Gástrica/fisiología , Mucosa Intestinal/fisiología , Duodeno/lesiones , Duodeno/metabolismo , Mucosa Gástrica/lesiones , Mucosa Gástrica/metabolismo , Microbioma Gastrointestinal/fisiología , Humanos , Mucosa Intestinal/lesiones , Mucosa Intestinal/metabolismo , Mucinas/fisiología , Permeabilidad , Factores ProtectoresRESUMEN
BACKGROUND: Hordeum vulgare L (barley) contains numerous phenolic substances with proven anticancer, antioxidant and gastroprotective activities. Saccharification increases the functionality and bioavailability of these compounds thus can aid in the development of a natural product based medicine. This study aimed to investigate the possible gastroprotective effects of saccharification on the indomethacin (IND)-induced gastric ulcers in rats using Weissella cibaria- and Saccharomyces cerevisiae-triple fermented H. vulgare extract (FBe). METHODS: In total, 60 healthy male 6-week old Sprague-Dawley SD (SPF/VAF Outbred CrljOri:CD1) rats were commercially purchased. The FBe extract (100, 200, and 300 mg kg- 1) was orally administered 30 min before an oral treatment of IND (25 mg kg- 1). Six hours after IND treatment, variations in the histopathology, myeloperoxidase (MPO) activity, gross lesion scores, lipid peroxidation, and antioxidant defense system component (superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)) levels were measured. RESULTS: FBe treatment showed significant (p < 0.01 or p < 0.05) and dose-dependent decrease in gastric mucosal damage. In the present study hemorrhagic gross lesions, gastric MPO activity, and histopathological gastric ulcerative lesions were observed in IND-treated rats compared to the IND control rats. In particular, FBe, in a dose-dependent manner, strengthened the antioxidant defense systems, decreased lipid peroxidation and CAT activity by increasing the GSH levels and SOD activity, respectively. The 200 mg kg- 1 dose of FBe was similarly gastroprotective as the 10 mg kg- 1 dose of omeprazole in rats with IND-induced gastric mucosal damage. CONCLUSIONS: The findings of the present study show that an oral administration of FBe had positive gastroprotective effects through strengthening the body antioxidant defense system and anti-inflammatory effects.
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Antioxidantes/farmacología , Mucosa Gástrica/efectos de los fármacos , Hordeum/química , Indometacina/efectos adversos , Extractos Vegetales/farmacología , Animales , Fermentación , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Oxidorreductasas/metabolismo , Ratas , Ratas Sprague-Dawley , Úlcera GástricaRESUMEN
Turmeric obtained from the rhizomes of Curcuma longa has been used in the prevention and treatment of many diseases since the ancient times. Curcumin is the principal polyphenol isolated from turmeric, which exhibits anti-inflammatory, antioxidant, antiapoptotic, antitumor, and antimetastatic activities. The existing evidence indicates that curcumin can exert a wide range of beneficial pleiotropic properties in the gastrointestinal tract, such as protection against reflux esophagitis, Barrett's esophagus, and gastric mucosal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) and necrotizing agents. The role of curcumin as an adjuvant in the treatment of a Helicobacter pylori infection in experimental animals and humans has recently been proposed. The evidence that this turmeric derivative inhibits the invasion and proliferation of gastric cancer cells is encouraging and warrants further experimental and clinical studies with newer formulations to support the inclusion of curcumin in cancer therapy regimens. This review was designed to analyze the existing data from in vitro and in vivo animal and human studies in order to highlight the mechanisms of therapeutic efficacy of curcumin in the protection and ulcer healing of the upper gastrointestinal tract, with a major focus on addressing the protection of the esophagus and stomach by this emerging compound.
Asunto(s)
Curcumina/farmacología , Enfermedades del Esófago/tratamiento farmacológico , Enfermedades del Esófago/etiología , Sustancias Protectoras/farmacología , Gastropatías/tratamiento farmacológico , Gastropatías/etiología , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Curcumina/uso terapéutico , Evaluación Preclínica de Medicamentos , Enfermedades del Esófago/diagnóstico , Enfermedades del Esófago/metabolismo , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Humanos , Sustancias Protectoras/uso terapéutico , Transducción de Señal/efectos de los fármacos , Gastropatías/diagnóstico , Gastropatías/metabolismo , Estrés Fisiológico/efectos de los fármacosRESUMEN
The gastroprotective potential of the methanolic extracts from peels (MEPe), seeds (MESe) and pulp (MEPu) of Chrysophyllum cainito L. (Sapotaceae) fruits was evaluated in mice using ethanol/HCl- and indomethacin-induced ulcer, as well as the antiulcer effect of the juice and flour from this fruit. The lowest oral gastroprotective dose of MEPe, MESe and MEPu against ethanol/HCl was 3, 3 and 10 mg/kg, respectively. Moreover, all extracts increased mucin secretion at 176, 198 and 193%. Intraperitoneal administration of MEPe (0.3 mg/kg), MESe (0.3 mg/kg) and MEPu (1 mg/kg) also promoted gastroprotection against ethanol/HCl. In addition, MEPe (3 mg/kg, p.o), MESe (3 mg/kg, p.o) and MEPu (10 mg/kg, p.o) reduced indomethacin-induced gastric ulcer in mice by 78, 70 and 50%, respectively. Regarding the mode of action, the gastroprotective effect of MEPe was decreased by the pre-administration of N-ethylmaleimide (NEM, a sulfhydryl group chelator, 10 mg/kg, i.p), glibenclamide (a potassium channel blocker, 10 mg/kg, i.p), yohimbine (10 mg/kg, i.p, an alpha-adrenergic receptor antagonist, 10 mg/kg, i.p) and indomethacin (a cyclooxygenase inhibitor, 10 mg/kg, i.p). The gastroprotective effect of MESe was reduced by the pre-administration of NEM, glibenclamide, N-Nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor, 70 mg/kg, i.p) and yohimbine, while MEPu had the gastroprotective effect decreased in animals pretreated with NEM and L-NAME. However, the extracts did not reduce gastric acid secretion. The supplementation with the flour from C. cainito fruit at 10% by 7 days, but not the juice intake, displayed gastroprotective potential, evidencing the fruit as a promising functional food. Together, the antiulcer effect of extracts of the C. cainito fruit in different experimental models was confirmed by the favoring of mucosal protective mechanisms among different, but complementary, modes of action. In parallel, the gastroprotective effects of the flour from C. cainito fruit were also described.
Asunto(s)
Antiulcerosos/farmacología , Frutas/química , Mucosa Gástrica/efectos de los fármacos , Sapotaceae/química , Úlcera Gástrica/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Etanol/química , Femenino , Indometacina/farmacología , Ratones , NG-Nitroarginina Metil Éster/farmacología , Fitoterapia/métodos , Extractos Vegetales/farmacología , Hojas de la Planta/químicaRESUMEN
Peptic ulcers are currently treated with various drugs, all having serious side effects. The aim of this study was to evaluate the gastroprotective activity of calein D (from Calea urticifolia), a sesquiterpene lactone with a germacrane skeleton. Gastric lesions were induced in mice by administering ethanol (0.2 mL) after oral treatment with calein D at 3, 10 and 30 mg/kg, resulting in 13.15 ± 3.44%, 77.65 ± 7.38% and 95.76 ± 2.18% gastroprotection, respectively, to be compared with that of the control group. The effect found for 30 mg/kg of calein D was not reversed by pretreatment with NG-nitro-l-arginine methyl ester (l-NAME, 70 mg/kg, ip), indomethacin (10 mg/kg, sc) or N-ethylmaleimide (NEM, 10 mg/kg, sc). Hence, the mechanism of action of calein D does not involve NO, prostaglandins or sulfhydryl compounds. Calein D was more potent than carbenoxolone, the reference drug. The findings for the latter are in agreement with previous reports.
Asunto(s)
Asteraceae/química , Etanol/efectos adversos , Lactonas/administración & dosificación , Sesquiterpenos de Germacrano/administración & dosificación , Úlcera Gástrica/prevención & control , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Etilmaleimida/administración & dosificación , Etilmaleimida/farmacología , Indometacina/administración & dosificación , Indometacina/farmacología , Lactonas/química , Lactonas/farmacología , Ratones , Estructura Molecular , NG-Nitroarginina Metil Éster/administración & dosificación , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Prostaglandinas/metabolismo , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismo , Compuestos de Sulfhidrilo/metabolismoRESUMEN
BACKGROUND: A low dose of capsaicin and its natural homologs and analogs (capsaicinoids) have shown to prevent development of gastric mucosal damage of alcohol and non-steroid anti-inflammatory drugs. Based on this experimental observation, a drug development program has been initiated to develop per os applicable capsaicin containing drugs to eliminate gastrointestinal damage caused by non-steroid anti-inflammatory drugs. METHODS: As a part of this program, a sensitive and selective reverse-phase high-performance liquid chromatography-based method with fluorescence detection has been developed for quantification of capsaicin and dihydrocapsaicin in experimental dog's plasma. RESULTS: The method was evaluated for a number of validation characteristics (selectivity, repeatability, and intermediate precision, LOD, LOQ, and calibration range). The limit of detection (LOD) was 2 ng/mL and the limit of quantification (LOQ) was 10 ng/mL for both capsaicin and dihydrocapsaicin. The method was used for analysis of capsaicin and dihydrocapsaicin in the plasma samples obtained after per os administration of low doses (0.1, 0.3, and 0.9 mg/kg bw) of Capsaicin Natural (USP 29) to the experimental animals. CONCLUSIONS: The obtained results indicated that the administered capsaicinoids did not reach the general circulation.
Asunto(s)
Capsaicina/química , Capsaicina/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/farmacología , Animales , Capsaicina/toxicidad , Cromatografía Líquida de Alta Presión , Perros , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Límite de Detección , Estructura Molecular , Reproducibilidad de los Resultados , Estómago/efectos de los fármacos , ToxicocinéticaRESUMEN
The protective effect of N-acetylcysteine (NAC) and genistein (GEN) on an experimental model of indomethacin (IND)-induced gastric injury was investigated. A total of 50 male rats were divided into 5 groups: (1) control, (2) IND, (3) NAC pretreated, (4) GEN pretreated, and (5) NAC+GEN pretreated. Rats in groups 3-5 were orally administered NAC (500 mg/kg), GEN (10 mg/kg), or both, respectively, once daily for 7 days before the induction of gastric injury by IND (50 mg/kg). The stomach was removed for biochemical analysis and histopathological examination. Pretreatment with NAC, GEN, or both significantly improved ulcer indices and increased nitric oxide level and superoxide dismutase activity. They also significantly decreased malondialdehyde, tumour necrosis factor α levels, and myeloperoxidase activity, and downregulated matrix metalloproteinase 9 (MMP-9) gene expression compared to the IND group. NAC alone ameliorated IND-induced apoptosis, whereas GEN only significantly increased prostaglandin E2 level. Further, coadministration of both resulted in a significantly better gastroprotective effect versus solo administration. Coadministration of NAC and GEN has an additive gastroprotective effect in IND-induced gastric injury, which may be through interaction of their potential cytoprotective, antioxidant, anti-inflammatory, and antiapoptotic mechanisms together with regulation of MMP-9 expression.