Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 13.708
Filtrar
1.
Pharm Biol ; 60(1): 600-608, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35277113

RESUMO

CONTEXT: Amauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with medicinal properties. However, the effects of A. rugosum on gastric ulcer remain unclear. OBJECTIVE: To investigate the gastroprotective efficacy of water extract of A. rugosum (WEA) on gastric ulcer. MATERIALS AND METHODS: Sprague-Dawley rats were randomly grouped as control, model, lansoprazole and 200, 100 and 50 mg/kg of WEA. After pre-treatment for seven days, ethanol- and indomethacin-induced gastric ulcer models were established. The gastric ulcer and histopathology were investigated. Enzyme-linked immunosorbent assay (ELISA), quantitative polymerase chain reaction (Q-PCR) and Western blot assays were conducted to explore the potential anti-inflammatory effect and mechanism of WEA. Additionally, the pyloric ligation model was used to explore the influence of WEA on gastric acid and mucus. RESULTS: Pre-treatment with WEA (200, 100 and 50 mg/kg) effectively reduced ulcerous area in both ethanol-induced (71%, 88% and 71%) and indomethacin-induced (77%, 65% and 86%) gastric ulcer model. The gastric levels of tumour necrosis factor-alpha (TNF-α) (34% and 50 mg/kg), interleukin-6 (IL-6) (32% and 100 mg/kg) and interleukin-1ß (IL-1ß) (36%, 45% and 41%) were reduced significantly (p < 0.05) by WEA. Serum nitric oxide was decreased significantly (p < 0.05) at 200 and 50 mg/kg and PGE2 concentration was increased remarkably (p < 0.05) at 100 mg/kg. Gene expression of inflammasome Nlrp3, and the nuclear translocation of nuclear factor-κB (NF-κB) P65 were significantly decreased by WEA pre-treatment. However, the pH of gastric acid and secretion of mucus did not show any significant change. CONCLUSIONS: The gastroprotective effect of WEA on gastric damage is attributed to anti-inflammation through the inhibition on NF-κB P65 nuclear migration and Nlrp3 gene expression.


Assuntos
Anti-Inflamatórios/farmacologia , Antiulcerosos/farmacologia , Polyporaceae/metabolismo , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/administração & dosagem , Antiulcerosos/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/patologia , Fator de Transcrição RelA/metabolismo , Água/química
2.
Eur J Pharmacol ; 922: 174891, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35288192

RESUMO

Apoptosis of gastric mucosa epithelial cells caused by the abuse of alcohol produces injury to the gastric mucosa and acute or chronic gastritis. In recent years, it has been demonstrated that endoplasmic reticulum stress (ERS) is involved in mediating apoptosis, and that autophagy has a protective effect on survival of cells. Rebamipide is a gastric mucosal protectant used to treat gastritis and stomach ulcers. In this study, ethanol was used to overstimulate gastric mucosal epithelial cells and gavage mice. It was found that 400 mmol/L ethanol overstimulation could activate ERS and induce apoptosis (control vs ethanol treatment: 15.24 ± 1.10% vs 33.80 ± 1.47%, P < 0.001); but could not activate the autophagy pathway. Rebamipide intervention can reduce apoptosis rate (20.78 ± 1.63%), and significantly inhibit the activation of ERS and the active ERS-related downstream NF-κB signaling pathway. Additionally, rebamipide can activate the expression of autophagy-related pathway proteins and increase the expression of p-ERK and p-p38. In addition, rebamipide relieved oxidative stress after an ethanol insult. In the present study, molecular evidence of rebamipide inhibition of ERS and regulation of the protein expression of autophagy pathway components were produced using an acute alcoholic gastric mucosal injury model. This model provides a new approach for investigating the effects of rebamipide treatment on alcohol-induced gastric mucosal damage.


Assuntos
Antiulcerosos , Gastrite , Alanina/análogos & derivados , Alanina/farmacologia , Alanina/uso terapêutico , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Proteínas Relacionadas à Autofagia/metabolismo , Estresse do Retículo Endoplasmático , Células Epiteliais , Etanol/farmacologia , Mucosa Gástrica , Gastrite/induzido quimicamente , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Camundongos , Quinolonas
3.
Molecules ; 27(5)2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35268666

RESUMO

Myrtus communis L. essential oil (EO), mainly composed of myrtenyl acetate (30.6%), linalool (14.9%), α-pinene (11.10%) and 1,8-cineole or eucalyptol (9.9%), was microencapsulated with maltodextrin by emulsification and spray-drying, reaching a yield and efficiency of 43.7 and 48.7%, respectively. The microencapsulated myrtle EO (MMEO) was then evaluated regarding its gastroprotective activity in a model of ethanol/HCl-induced acute gastric ulcer in Wistar rats. Pretreatment with MMEO induced a remarkable inhibition of gastric lesions and acidity, correlated to high healing and protection percentages. Moreover, it exerted a potent anti-inflammatory effect on the gastric mucosa, counteracting EtOH-induced gastric lipoperoxidation and preventing the depletion of the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Taken together, the gastroprotective action of encapsulated MMEO may be multi-factorial, and ascribable, at least in parts, to its anti-inflammatory and antioxidant properties.


Assuntos
Antiulcerosos , Myrtus , Óleos Voláteis , Úlcera Gástrica , Animais , Antiulcerosos/farmacologia , Etanol/efeitos adversos , Mucosa Gástrica , Óleos Voláteis/uso terapêutico , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia
4.
J Ethnopharmacol ; 292: 115191, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35292374

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The use of mushrooms in medicine is quite old and the first report about the use of genus Agaricus in treatment of ulcers occurred in Byzantine period. This mushroom is widely consumed as food, tea, food supplements, as well as nutraceutical and cosmeceutical applications, being cultivated and appreciated in several countries such as Brazil, Korea, Japan and China. AIM OF THE STUDY: This study aimed to characterize the chemical profile and the potential gastroprotective effect of hydroalcoholic extract from Agaricus blazei Murill (HEAb). MATERIALS AND METHODS: The extract was chemically characterized by elemental analysis, UPLC-QTOF-MSE, Nuclear Magnetic Resonance (NMR) and high-performance liquid chromatography (HPLC) techniques to elucidate the metabolites present in the extract. The quantification of phenolic compounds and the in vitro antioxidant activities were performed and the gastroprotective effect of this extract was evaluated against ethanol-induced gastric ulcer model. HEAb was administered by gavage at 5, 25 and 50 mg kg-1 and N-acetylcysteine at 300 mg kg-1 (positive control). Furthermore, the pathways of nitric oxide (NO), Cyclic Guanylate Monophosphate (cGMP), prostaglandins (PGs) and the involvement of ATP-sensitive K+ Channels were modulated. RESULTS: Mannitol, malic acid, pyroglutamic acid, L-agaritine and L-valine were putatively identified by UPLC-QTOF-MSE in HEAb. In addition, it was possible to identify mannitol by the intense signals in the NMR spectra, being still quantified as the main compound in the extract by HPLC. The contents of total phenols and flavonoids corroborated with the good antioxidant activity of HEAb. This study observed that HEAb at 25 and 50 mg kg-1 had gastroprotection effect demonstrated by the reduction of histopathological parameters and the reduction of mastocytosis in the stomach of mice. CONCLUSIONS: In this study was possible to conclude that HEAb has gastroprotective effect related to the involvement of NO and PG pathways in the ethanol-induced gastric ulcer model in mice.


Assuntos
Agaricus , Antiulcerosos , Úlcera Gástrica , Agaricus/metabolismo , Animais , Antiulcerosos/química , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Etanol/química , Mucosa Gástrica , Manitol/metabolismo , Manitol/farmacologia , Manitol/uso terapêutico , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle
5.
Int Immunopharmacol ; 107: 108673, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35259712

RESUMO

Lindera reflexa Hemsl. (LR) has been used for the treatment of gastrointestinal disorders. The present study was carried out to investigate the gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. (LRG) on ethanol-induced gastric ulcer in rats and its possible mechanisms. The ulcer area was measured, and samples of gastric tissue were taken for histochemical, pathological, and biochemical analyses. Pretreatment with LRG protected the gastric mucosa as seen by reduction the GUI and gastric juice volume, regulated gastric acid secretion. LRG counteracted the ethanol-induced oxidative stress by increasing the levels of depleted SOD and CAT as well as significantly attenuating the lipid peroxidation by reducing the levels of MDA and MPO. LRG also reduced release of inflammatory mediator TNF-α, increased the content of PGE2 and inhibited MTL secretion. Immunofluorescence and Western blot analyses confirmed that the co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LRG-treated rats was significantly lower than that of rats with gastric ulcers. Furthermore, LRG also modulated the expression of Ki-67 antigens. LRG markedly increased the expression of phosphorylated form of extracellular signal-regulated kinaseVEGFR2, ERK1/2, AKT and p38, thereby protecting the gastric mucosa. These findings indicated that the gastroprotective effect of LRG is attributable to its antioxidant, anti-inflammatory, and antisecretory properties. In addition, LRG can ameliorate ethanol-induced gastric ulcers in rats by regulating the VEGFR2/ERK and TLR-2/MyD88 signaling pathways.


Assuntos
Antiulcerosos , Lindera , Úlcera Gástrica , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Etanol/metabolismo , Etanol/toxicidade , Mucosa Gástrica , Lindera/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Ratos , Transdução de Sinais , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Receptor 2 Toll-Like/metabolismo
6.
J Ethnopharmacol ; 289: 115055, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35101571

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium aromaticum L. volatile oil (clove oil) has been traditionally used for various stomach disorders including inflammatory conditions. Eugenol is the major constituent present in the volatile oil, and it has been established as a gastroprotective agent through many published studies, but the exact and complete mechanism of ulcer protection is not delineated yet. Moreover, it plays precisely the opposite effect in higher dose in antiulcer properties with worsening the ulcer at a higher dose. AIM: This study aims to carry out the prophylactic cytoprotective effect of eugenol with single low doses and explore the probable interrelated underlying transcriptional and translational level mechanism of cytoprotection such as antioxidative, anti-inflammatory, mucous generation in rats using ethanol-induced ulcer model. METHODS: Rats were administered with different doses of eugenol before ethanol intragastrically. The effects of the eugenol on mucous production, Nitric oxide generation, PGE2 synthesis, lipid peroxidation were recorded together with cytokines measurement in the blood. TNF-α and IL-6, two key cytokines, were also studied in specific. In addition, studies on the immunohistochemical and gene expression of HSP70 and iNOS indicators have been conducted. RESULTS: According to our findings, Eugenol substantially reduced the ulcer index and completely protected the mucosa from lesions. By restoring the lowered GSH and NP-SH levels, the protective effect of the eugenol was found to be augmented at both doses. This finding has corresponded to an increase in MDA, which was lowered by ethanol administration. Pre-treatment with eugenol on the ethanol-induced ulcer reduced the plasma NO levels and increased PGE2 along with a decreased TNF-α and IL-6 concentration. Additionally, significant transcriptional and translational upregulation of HSP70 and downregulation of iNOS were detected in the eugenol-treated rat stomach tissue. CONCLUSION: Our findings demonstrated that eugenol had a considerable gastroprotective impact at low doses, which could be attributed to its ability to regulate inflammatory reactions and antioxidant capacity.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Eugenol/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/administração & dosagem , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Antioxidantes/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/toxicidade , Eugenol/administração & dosagem , Masculino , Malondialdeído/metabolismo , Ratos , Ratos Sprague-Dawley
8.
World J Gastroenterol ; 28(1): 23-46, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35125818

RESUMO

The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes. Summarized are all these arguments, in the Robert's cytoprotection concept, to substantiate the resolution of different major vessel occlusion disturbances, in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome, which was obtained by BPC 157 therapy. Conceptually, there is a new point, namely, endothelium maintenance to epithelium maintenance (the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow or bypass the occluded or ruptured vessel). In this paper, we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157, which is stable in the human gastric juice, is a membrane stabilizer and counteracts gut-leaky syndrome. As a particular target, it is distinctive from the standard peptide growth factors, involving particular molecular pathways and controlling VEGF and NO pathways. In the early 1990s, BPC 157 appeared as a late outbreak of the Robert's and Szabo's cytoprotection-organoprotection concept, like the previous theoretical/practical breakthrough in the 1980s and the brain-gut axis and gut-brain axis. As the time went on, with its reported effects, it is likely most useful theory practical implementation and justification. Meantime, several reviews suggest that BPC 157, which does not have a lethal dose, has profound cytoprotective activity, used to be demonstrated in ulcerative colitis and multiple sclerosis trials. Likely, it may bring the theory to practical application, starting with the initial argument, no degradation in human gastric juice for more than 24 h, and thereby, the therapeutic effectiveness (including via a therapeutic per-oral regimen) and pleiotropic beneficial effects.


Assuntos
Antiulcerosos , Síndrome de Budd-Chiari , Traumatismo por Reperfusão , Humanos , Fragmentos de Peptídeos , Proteínas , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle
9.
J Vet Sci ; 23(2): e19, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35187877

RESUMO

BACKGROUND: Gastric ulcer is one of the prevalent diseases in racehorses. However, it has not been recognized as important in Korea, and drugs used to treat gastric ulcers are included in the doping test list, so they are not allowed to be administered to racehorses in training. OBJECTIVES: This study was performed 1) to investigate the prevalence and the severity of gastric ulcers in Thoroughbred racehorses in Korea, 2) to confirm the therapeutic effect of ranitidine and omeprazole, and 3) to compare the efficacy between ranitidine and omeprazole. METHODS: Forty-nine horses were randomly recruited, and gastroscopy was performed within two days after racing. Twelve horses with a sum grade of five or higher were randomly assigned to two treatment groups. Seven horses were administered ranitidine, and five horses were administered omeprazole. Follow-up gastroscopy was scheduled within one to five days after finishing the treatment. RESULTS: The prevalence of gastric ulcer in Korean Thoroughbred racehorses after racing was 100%, and the grade was more severe in the non-glandular region than in the pyloric region. There was no correlation between the severity of gastric ulcer in the two regions. Omeprazole had a greater therapeutic effect than ranitidine. CONCLUSIONS: This study shows the importance of recognizing gastric ulcers as an important factor, and omeprazole as a possible treatment option in Korea, as it has been removed from the list of prohibited substances for racehorses. Thus, the use of omeprazole is currently recommended until one day before the race.


Assuntos
Antiulcerosos , Doenças dos Cavalos , Úlcera Gástrica , Animais , Antiulcerosos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/epidemiologia , Cavalos , Omeprazol/uso terapêutico , Prevalência , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/epidemiologia , Úlcera Gástrica/veterinária
10.
Biomed Res Int ; 2022: 9246785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35111849

RESUMO

OBJECTIVE: The present study was aimed at investigating the possible antiulcer activities of some natural phytochemicals Aloe perryi leaf extract (APLE) and flower extract (APFE) in addition to the date palm seed extract (DPSE) and the oily samples of DPSE in a pylorus ligation-induced ulcer model using ranitidine as a standard antiulcer drug. BACKGROUND: Peptic ulcer is a prevalent gastrointestinal disorder due to hypersecretion of gastric acid. It affects four million people worldwide, and 2-10% of these ulcers are perforated and cause bleeding. This increases the risk of morbidity and mortality. So we aimed to introduce a primary study alternatively safe method for treating peptic ulcer. MATERIALS AND METHODS: Forty-two Wistar Albino rats of either sex were randomly divided into seven groups (6/each). The pylorus ligation was done to induce ulcer in pretreated albino rats. The antiulcer activities of extracts were estimated at different dose levels (250 and 500 mg/kg) using ranitidine as a standard drug (50 mg/kg). Gastric volume, pH, and total and free acidity as well as ulcer index and percentage of ulcer inhibition were measured to elucidate the antiulcerogenic effects. Histological examination of gastric ulcer was also performed. Statistical analysis for the results was done where P < 0.05 was considered statistically significant. RESULTS: Pylorus ligation for 6 h in control rats resulted in gastric ulcer which was indicated by the accumulation of gastric secretion and increased total acidity and decreased pH. The pretreatment of rats with APLE, APFE, and DPSE in addition to the oily samples of DPSE significantly inhibited the ulcers induced by pylorus ligation. These effects were attributed to significant reductions in total and free acidity, ulcer index, and gastric volume while there is a marked decrease in gastric pH (the antisecretory) as well as mucosal strengthening properties of these phytochemicals. CONCLUSION: These findings give these extracts the potential to be a promising tool for the management of gastric ulcer after performing further clinical and experimental studies. Our study demonstrated the promising antiulcer activity of extracts and oils in pyloric ligation-induced gastric ulcer. To the best of our knowledge, this is the first study to explore the antiulcer activity of these extracts; however, further investigations may be recommended for full details about this antiulcerogenic capacity.


Assuntos
Aloe , Phoeniceae , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Concentração de Íons de Hidrogênio , Extratos Vegetais/administração & dosagem , Ranitidina/administração & dosagem , Ranitidina/farmacologia , Ratos , Ratos Wistar
11.
Carbohydr Polym ; 278: 118925, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973743

RESUMO

In this study, new stimuli - responsive hybrid hydrogels were achieved via succinylated cellulose nanocrystals (Su-CNC). The innovation was concerned with the inclusion of Su-CNC, at different degree of substitution (DS), into hydrogel network to render it pH and thermo-responsive characters through free radical polymerization reaction with poly(N-isopropylacrylamide) (PNIPAm). The prepared hydrogel was also examined for the in vitro release of Famotidine at different pH values. As clearly evident from the results, all the hydrogels prepared with different DS of Su-CNC, which were nominated as Su-CNC / PNIPAm (1-3), showed a high response to temperature change since their swelling behavior and hydrophilicity were decreased at 35 °C and upwards. This led to the more hydrophobicity character and thus the hydrogel shrinkage occurred. On the other hand, at pH 6, the hydrogels exhibited a significant Equilibrium Swelling Ratio (ESR) attaining 18.1, 17.3 and 16.8 (g/g) for Su-CNC / PNIPAm (1-3), respectively. However, Su-CNC / PNIPAm 2 hydrogel showed a significant response to the pH change from 8 to 2 which was advised to be selected as a potential pH responsive hydrogel for the in vitro Famotidine release.


Assuntos
Antiulcerosos/química , Celulose/química , Famotidina/química , Hidrogéis/química , Nanopartículas/química , Temperatura , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular
12.
Arq Bras Cir Dig ; 34(3): e1587, 2022.
Artigo em Inglês, Português | MEDLINE | ID: mdl-35019113

RESUMO

BACKGROUND: The physiological stress of critically ill patients can trigger several complications, including digestive bleeding due to stress ulcers (DBSU). The use of acid secretion suppressants to reduce their incidence has become widely used, but with the current understanding of the risks of these drugs, their use, as prophylaxis in critically ill patients, is limited to the patients with established risk factors. AIM: To determine the appropriateness of the use of prophylaxis for stress ulcer bleeding in acutely ill patients admitted to intensive care units and to analyze the association of risk factors with adherence to the prophylaxis guideline. METHODS: Retrospective, analytical study carried out in three general adult intensive care units. Electronic medical records were analyzed for epidemiological data, risk factors for DBSU, use of stress ulcer prophylaxis, occurrence of any digestive bleeding and confirmed DBSU. The daily analysis of risk factors and prophylaxis use were in accordance with criteria based on the Guidelines of the Portuguese Society of Intensive Care for stress ulcer prophylaxis. RESULTS: One hundred and five patients were included. Of the patient days with the opportunity to prescribe prophylaxis, compliance was observed in 95.1%. Of the prescription days, 82.35% were considered to be of appropriate use. Overt digestive bleeding occurred in 3.81% of those included. The occurrence of confirmed DBSU was identified at 0.95%. Multivariate analysis by logistic regression did not identify risk factors independently associated with adherence to the guideline, but identified risk factors with a negative association, which were spinal cord injury (OR 0.02 p <0.01) and shock (OR 0.36 p=0.024). CONCLUSION: The present study showed a high rate of adherence to stress ulcer prophylaxis, but with inappropriate use still significant. In the indication of prophylaxis, attention should be paid to patients with spinal cord injury and in shock.


Assuntos
Antiulcerosos , Úlcera , Adulto , Humanos , Unidades de Terapia Intensiva , Prescrições , Estudos Retrospectivos , Fatores de Risco
13.
Biomarkers ; 27(3): 247-257, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34978233

RESUMO

CONTEXT: Gastric ulcer is regarded as one of the main clinical ailments with high morbidity and mortality rates. MATERIALS AND METHODS: Gastro-protective effect of Artemisia sieberi essential oil (AS-EO) in ethanol-induced rats was evaluated via biochemical, histopathological and large-scale metabolomics analyses. Glutathione (GSH), total antioxidant capacity (TAC), prostaglandin (PGE2) and tumour necrosis factor α (TNF-α) alongside with histopathological examination of gastric mucosa were analysed. Metabolites profiling coupled to Global Natural Products Social molecular networking platform (GNPS) and multivariate data analyses to reveal for changes in rats metabolome with treatments and involved action mechanisms. RESULTS: Pre-treatment with 100 and 200 mg/kg of AS-EO in EtOH-treated rats restored all parameters towards normal status compared to disease model. AS-EO alleviated the histological and pathological damage of gastric tissue caused by ethanol. Metabolites profiling revealed an increase in uracil, cholesterol and fatty acids/fatty acyl amides levels in ulcer rats and restored to normal levels post AS-EO intervention. These results indicated the efficacy of AS-EO in a dose-dependent manner, and to exert protective effects in ulcer rat model by targeting several metabolic pathways viz. lipid, energy, and nucleotide metabolisms. CONCLUSION: AS-EO adds to the known uses of genus Artemisia as anti-ulcerogenic agent by attenuating oxidative stress and inflammatory responses associated with an ulcer. Several novel biomarkers for ulcer progression in rats were identified and have yet to be confirmed in human models.


Assuntos
Antiulcerosos , Artemisia , Óleos Voláteis , Animais , Antiulcerosos/farmacologia , Etanol/farmacologia , Mucosa Gástrica , Humanos , Metabolômica , Óleos Voláteis/farmacologia , Ratos , Ratos Wistar , Úlcera/tratamento farmacológico , Úlcera/metabolismo , Úlcera/patologia
14.
Nat Prod Res ; 36(5): 1306-1310, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33331166

RESUMO

Chitosan is more prominent in food applications due to its versatile properties. Anthocyanins have gained much research attention due to their multifaceted role in preventing various lifestyle ailments. Encapsulated anthocyanin- loaded chitosan nanoparticles (ACNPs) were prepared by conventional ionotropic gelation method. In the present study, the gastro-protective effect of encapsulated ACNPs was evaluated against absolute ethanol-hydrochloric acid (HCl-Ethanol mixture) induced gastric ulcer in male Wistar rats. The histopathology and microscopic scoring of ulcer data of stomach tissue sections revealed that oral administration of encapsulated ACNPs group can alleviate inflammation of induced-gastric ulcer. Further, the expression of anti-inflammatory cytokines (Interleukin 4, IL-4) and suppression of pro-inflammatory cytokines (Interferon gamma, IFN-γ) confirm the cytoprotective effect of encapsulated ACNPs against HCl-Ethanol induced necrotic damage to mucosal membrane. The results of the present study indicate that the gastro protective action of encapsulated ACNPs ascribable to at least in parts to its anti-inflammatory property.[Formula: see text].


Assuntos
Antiulcerosos , Quitosana , Nanopartículas , Úlcera Gástrica , Animais , Antocianinas/metabolismo , Antocianinas/farmacologia , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Quitosana/metabolismo , Quitosana/farmacologia , Quitosana/uso terapêutico , Etanol/farmacologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera/tratamento farmacológico
16.
J Ethnopharmacol ; 284: 114752, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34662665

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Chinese medicine and a previous literature, many parts of Chinese sumac (Rhus chinensis Mill.), including fruits, are used as traditional herb to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. However, the effects of the fruits on the prevention of gastric ulcer and the underlying mechanisms have not been reported. AIM OF THE STUDY: This experiment aimed to investigate the preventive effect of ethanol extract (RM) from Chinese sumac fruits on indomethacin-induced gastric ulcer in mice and the underlying mechanisms. MATERIALS AND METHODS: A single gavage of indomethacin was used to induce a gastric ulcer model in Kunming male mice. According to the results of histopathological analysis, immunohistochemistry and immunofluorescence analysis, as well as the expression of prostaglandin E-2, antioxidant enzymes and cytokines, the protective effect of RM on indomethacin-induced gastric ulcer was evaluated. The expression levels of several key proteins involved in oxidative stress, inflammation and apoptosis in gastric tissue were detected to illuminate the underlying mechanisms. RESULTS: RM significantly reduced the ulcer index and pepsin activity, improved the microstructure of gastric mucosa and the prostaglandin E-2 content, restored the levels of glutathione and superoxide dismutase, and decreased the contents of malondialdehyde, advanced oxidation protein products, TNF-α, IL-1 ß and IL-6. Further experimental results showed that RM could improve the expression levels of HO-1 and NQO1 by activating the Nrf2 protein pathway to alleviate oxidative stress in gastric tissue. At the same time, RM significantly down-regulated the expressions of p-NF-κB, p-IκBα and iNOS to relieve inflammatory response, and inhibited the cellular apoptosis of gastric tissue by up-regulating Bcl-2 and down-regulating Bax and cleaved Caspase-3. CONCLUSIONS: The current work clarified that the ethanol extract from Chinese sumac fruits can improve the oxidative stress level, inflammatory response and cell apoptosis in gastric tissue by interfering with the expressions of several key regulatory proteins to prevent indomethacin-induced gastric ulcer in mice. This study may provide some insights and scientific evidence on the application of Chinese sumac fruits as a traditional herb to prevent or alleviate gastric ulcer.


Assuntos
Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Rhus/química , Úlcera Gástrica/prevenção & controle , Animais , Animais não Endogâmicos , Anti-Inflamatórios não Esteroides/toxicidade , Antiulcerosos/isolamento & purificação , Antiulcerosos/farmacologia , Apoptose/efeitos dos fármacos , Frutas , Indometacina/toxicidade , Inflamação/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente
17.
Bioorg Chem ; 119: 105485, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34959176

RESUMO

This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs8-13(L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non- ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski's rule of five. A molecular docking study showed that the hybrids8-13(L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Edema/tratamento farmacológico , Peritonite/tratamento farmacológico , Inibidores da Agregação Plaquetária/farmacologia , Úlcera/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Carragenina , Celecoxib/química , Celecoxib/farmacologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Lignanas/química , Lignanas/farmacologia , Masculino , Camundongos , Estrutura Molecular , Peritonite/induzido quimicamente , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Ratos , Relação Estrutura-Atividade , Triazóis/química , Triazóis/farmacologia , Úlcera/induzido quimicamente
18.
J AOAC Int ; 105(3): 675-687, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-34918094

RESUMO

BACKGROUND: Helicobacter pylori infection is a common cause of peptic ulcer disease and dyspepsia. In addition, it may result in gastric cancer and gastric mucosa associated lymphoid tissue lymphoma. First-line therapy usually consists of triple therapy containing clarithromycin or amoxicillin, one of the proton pump inhibitors, and metronidazole or tinidazole. In addition to the triple therapy, an analgesic is required to relieve pain such as naproxen. OBJECTIVE: A sensitive and selective method needs to be developed and validated for simultaneous determination of four drugs (amoxacillin, tinidazole, naproxen and lansoprazole), used for treating Helicobacter pylori infection, in their combined dosage forms. METHODS: With the aid of experimental design, the cited drugs were separated and quantified. HPLC with a diode array detector was used and metronidazole, one of the drugs also used for treatment, was the internal standard (IS). A Thermo Scientific BDS Hypersil C18 column (5 µm, 250 mm x 4.6 mm) with mobile phase composed of acetonitrile-water (40 + 60, by volume), pH 5 adjusted with phosphoric acid, at 30°C was used for the separation of the cited drugs. RESULTS: The method was linear over the concentration ranges 10-500 µg/mL for amoxacillin, 10-350 µg/mL for tinidazole, 10-250 µg/mL for naproxen, and 2-20 µg/mL for lansoprazole. The proposed method was fully validated according to International Conference of Harmonization (ICH) guidelines. Statistical analysis revealed no significant difference between the results obtained and the four reference methods for the investigated drugs. CONCLUSION: The method can be easily implemented in QC studies of the cited drugs in their dosage forms. HIGHLIGHTS: Experimental design was applied using Plackett-Burman design for preliminary screening of factors followed by Box-Behnken design for chromatographic method optimization.


Assuntos
Antiulcerosos , Infecções por Helicobacter , Helicobacter pylori , Amoxicilina , Antibacterianos , Antiulcerosos/uso terapêutico , Cromatografia Líquida de Alta Pressão/métodos , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Lansoprazol/uso terapêutico , Metronidazol , Naproxeno/uso terapêutico , Omeprazol/farmacologia , Omeprazol/uso terapêutico , Projetos de Pesquisa , Tinidazol/farmacologia , Tinidazol/uso terapêutico
19.
Molecules ; 26(24)2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34946594

RESUMO

Moringa oleifera (M. oleifera), which belongs to the Moringaceae family, is a common herb, rich in plant compounds. It has a variety of bioactive compounds that can act as antioxidants, antibiotics, anti-inflammatory and anti-cancer agents, etc., which can be obtained in different body parts of M. oleifera. Isothiocyanates (ITCs) from M. oleifera are one class of these active substances that can inhibit cancer proliferation and promote cancer cell apoptosis through multiple signaling pathways, thus curbing cancer migration and metastasis, at the same time they have little adverse effect on normal cells. There are multiple variants of ITCs in M. oleifera, but the predominant phytochemical is 4-(α-L-rhamnosyloxy)benzyl isothiocyanate, also known as moringa isothiocyanate (MIC-1). Studies have shown that MIC-1 has the possibility to be used clinically for the treatment of diabetes, neurologic diseases, obesity, ulcerative colitis, and several cancer types. In this review, we focus on the molecular mechanisms underlying the anti-cancer and anti-chronic disease effects of MIC-1, current trends, and future direction of MIC-1 based treatment strategies. This review combines the relevant literature of the past 10 years, in order to provide more comprehensive information of MIC-1 and to fully exploit its potentiality in the clinical settings.


Assuntos
Anti-Inflamatórios/farmacologia , Fármacos Antiobesidade/farmacologia , Antiulcerosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Hipoglicemiantes/farmacologia , Isotiocianatos/farmacologia , Anti-Inflamatórios/química , Fármacos Antiobesidade/química , Antiulcerosos/química , Antineoplásicos Fitogênicos/química , Humanos , Hipoglicemiantes/química , Isotiocianatos/química , Moringa oleifera/química
20.
Biochemistry (Mosc) ; 86(10): 1192-1200, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34903151

RESUMO

Omeprazole suppresses excessive secretion of gastric acid via irreversible inhibition of H+/K+-ATPase in the gastric parietal cells. Recent meta-analysis of data revealed an association between the use of proton pump inhibitors (PPIs) and increased risk of bone fractures, but the underlying molecular mechanism of PPI action remains unclear. In this study, we demonstrated that omeprazole directly influences bone metabolism using a unique in vitro bioassay system with teleost scales, as well as the in vivo model. The in vitro study showed that omeprazole significantly increased the activities of alkaline phosphatase and tartrate-resistant acid phosphatase after 6 h of incubation with this PPI. Expression of mRNAs for several osteoclastic markers was upregulated after 3-h incubation of fish scales with 10-7 M omeprazole. The in vivo experiments revealed that the plasma calcium levels significantly increased in the omeprazole-treated group. The results of in vitro and in vivo studies suggest that omeprazole affects bone cells by increasing bone resorption by upregulating expression of osteoclastic genes and promoting calcium release to the circulation. The suggested in vitro bioassay in fish scales is a practical model that can be used to study the effects of drugs on bone metabolism.


Assuntos
Escamas de Animais/efeitos dos fármacos , Carpa Dourada/metabolismo , Omeprazol/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Escamas de Animais/citologia , Escamas de Animais/metabolismo , Animais , Antiulcerosos/farmacologia , Cálcio/metabolismo , Linfocinas/metabolismo , Modelos Animais , Osteoblastos/metabolismo , Osteoclastos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...