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1.
Life Sci ; 259: 118272, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32800836

RESUMO

AIM: Vanadium, a trace element found in food and water sources has been previous reported to attenuate ulcer formation without much insight into its mechanism of action. This study highlights the mechanism by which vanadium exhibits its gastro-protective activity. MAIN METHODS: Eighty male Wistar rats (80-100 g) were randomized into 8 equal groups. Groups 1 (control) and 2 (Ulcerated control) received water only, groups 3-8 received vanadium at 5, 10, 25, 50, 100 and 200 ppm respectively in their drinking water for ten weeks. Gastric ulcer was thereafter induced in groups (2-8) via ischaemia-reperfusion (IR) technique. The stomachs were excised for macroscopic examination, evaluation of mucous content, oxidative stress markers, hydrogen/potassium (H+/K+) and calcium (Ca++) ATPases activities plus expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Vanadium at low doses inhibited IR induced gastric ulcer by 62.62% (10 ppm), 54.80% (25 ppm) and 43.50% (50 ppm). KEY FINDINGS: Low dose vanadium increased mucous content, superoxide dismutase, catalase, glutathione activities and nitrite concentrations compared to ulcerated control group. The observed increase in malondialdehyde, Ca++ and H+/K+ ATPase activities, iNOS and COX-2 expression following IR were significantly reduced by pretreatment with vanadium. SIGNIFICANCE: This study demonstrated that vanadium at low doses exhibit gastro-protective activities on IR induced gastric ulcer in rat model by inhibiting proton pump activities and decreasing expressions of iNOS and COX-2, thereby giving more insight into the protective action of vanadium.


Assuntos
Traumatismo por Reperfusão/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Vanádio/farmacologia , Animais , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Mucosa Gástrica/metabolismo , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Bombas de Próton/efeitos dos fármacos , Ratos , Ratos Wistar , Reperfusão , Estômago/fisiologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Superóxido Dismutase/metabolismo
2.
Rev. Asoc. Med. Bahía Blanca ; 30(1): 20-27, 20 de junio de 2020.
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1099865

RESUMO

Se evaluó la actividad gastroprotectora de la infusión proveniente de las hojas de Aloysia gratissima (Verbenaceae), especie nativa de interés medicinal que se desarrolla en el sudoeste bonaerense, utilizando un modelo de inducción de úlceras gástricas con etanol en ratones. Se realizó un tamizaje fitoquímico para detectar la presencia de compuestos que podrían ser responsables de la actividad gastroprotectora de la planta. Se determinó el contenido de fenoles totales y la capacidad atrapadora de radicales libres mediante el método del Folin-Ciocalteu y del 2,2'-difenil-1-picrilhidrazilo (DPPH), respectivamente. Los ensayos demostraron que la infusión de la planta, administrada por vía oral en dosis de 100, 500 y 1000 mg/kg, ejerció una gastroprotección significativa frente a la inducción de úlceras. Se detectó una actividad atrapadora de radicales libres de 47,5%, similar a la sustancia de referencia (BHT). El estudio fitoquímico detectó la presencia de flavonoides y otros polifenoles, sustancias con reconocida capacidad antioxidante. Estos metabolitos ejercen efectos protectores en diferentes modelos experimentales de inducción de úlceras mediante mecanismos que pueden involucrar la neutralización de radicales libres, lo que podría explicar la actividad gastroprotectora de la planta. Estos hallazgos requieren estudios adicionales de A. gratissima como una posible terapia frente a la úlcera gástrica. (AU)


The gastroprotective activity of the infusion from the leaves of Aloysia gratissima (Verbenaceae), a native species of medicinal interest growing in South West Buenos Aires, was evaluated in an ethanol-induced gastric ulcer model in mice. Phytochemical screening was carried out in order to determine the presence of compounds that could be responsible for the pharmacological effects of the plant. Total phenolic content and the free radical scavenging activity of the plant were determined using the Folin-Ciocalteu and the 2,2'-diphenyl1-picrylhydrazyl (DPPH) method, respectively. Assays demonstrated that the infusion, orally administered at 100, 500, and 1000 mg/kg doses, exerted a significant gastroprotection effect against ulcer induction (P<0,05). A free radical scavenging activity of 47.5% -similar to the reference substance (BHT)- was detected. Phytochemical screening revealed the presence of antioxidant compounds such as flavonoids and other phenolic compounds. These compounds exert protective effects in different experimental models of ulcer induction that could involve free radical neutralization, which could explain the gastroprotective activity of the plant. These promising results support additional studies of A. gratissima as a potential therapy against gastric ulcer. (AU)


Assuntos
Animais , Camundongos , Úlcera Gástrica/tratamento farmacológico , Verbenaceae/efeitos dos fármacos , Experiências Laboratoriais , Radicais Livres/farmacologia
3.
AAPS PharmSciTech ; 21(5): 137, 2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32419124

RESUMO

In the global incidence of peptic ulcer, with the associated rates of hospitalizations and mortality are increasing, in the United States, peptic ulcer disease affects approximately 4.6 million people annually, with an estimated 10% of the US population having evidence of a duodenal ulcer. The present research aims to find a novel treatment for ethanol induced ulcer by loading thymoquinone (TQ) on a nanostructured lipid carrier (NLC), using Compritol® 888 and coconut oil. The TQ-loaded coconut oil NLC was formulated using melt emulsification combined with a sonication method using Poloxamer 188 as a surfactant. Finally, the optimization of the formulations was performed on a three-factor, three-level Box-Behnken statistical design, with 85.63% entrapment efficiency of TQ in the optimized formulation. A biphasic release pattern of the formulation was recorded in an in vitro drug release study, where the initial burst release of the drug was observed in the first 2 h, followed by a gradual release. Later, the TQ-loaded coconut oil NLC was found to protect the gastric mucous membrane more effectively (78.95% in.; p < 0.01) in an alcohol-induced ulcer model, whereas the TQ suspension showed 30.87% inhibition (p < 0.05) of the ulcerative index, when compared with the ulcer control group. The histopathological evaluations of the stomach in ulcer-induced animals demonstrated protection potential of TQ-loaded coconut oil NLC against an alcohol-induced gastric ulcer. In a nutshell, the entrapment of TQ within the NLC was found to deliver the entrapped drug more effectively when administered through an oral route to possess a gastroprotective effect.


Assuntos
Benzoquinonas/administração & dosagem , Óleo de Coco/química , Etanol , Lipídeos/química , Nanoestruturas/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Animais , Benzoquinonas/química , Portadores de Fármacos , Emulsões , Ácidos Graxos , Masculino , Tamanho da Partícula , Poloxâmero , Ratos , Ratos Sprague-Dawley , Sonicação , Tensoativos
4.
Int J Nanomedicine ; 15: 2529-2539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32346290

RESUMO

Background: Peptic ulcer disease, a painful lesion of the gastric mucosa, is considered one of the most common gastrointestinal disorders. This study aims to investigate the formulation of pumpkin seed oil (PSO)-based nanostructured lipid carriers (NLCs) to utilize PSO as the liquid lipid component of NLCs and to achieve oil dispersion in the nano-range in the stomach. Methods: Box-Behnken design was utilized to deduce the optimum formula with minimum particle size. The optimized PSO-NLCs formula was investigated for gastric ulcer protective effects in Wistar rats by evaluating ulcer index and determination of gastric mucosa oxidative stress parameters. Results: PSO was successfully incorporated as the liquid lipid (LL) component of NLCs. The prepared optimum PSO-NLCs formula showed a size of 64.3 nm. Pretreatment of animals using the optimized PSO-NLCs formula showed significantly (p< 0.001) lower ulcer index compared to indomethacin alone group and significantly (p<0.05) less mucosal lesions compared to the raw oil. Conclusion: These results indicated great potential for future application of optimized PSO-NLCs formula for antiulcer effect in non-steroidal anti-inflammatory drug (NSAID)-induced gastric ulcer.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Cucurbita/química , Portadores de Fármacos/química , Lipídeos/química , Nanoestruturas/química , Óleos Vegetais/química , Úlcera Gástrica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Indometacina/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/patologia
5.
Int J Nanomedicine ; 15: 1187-1203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32110016

RESUMO

Background: Selenium (Se) is an indispensable trace element required for animals and human beings, whereas Se-deficiency can accelerate the development of acute gastric injury induced by over-consumption of alcohol. Selenium nanoparticles (SeNPs), as a special Se-supplement with favorable properties and unique bioactivities, are expected to play a passive role in gastroprotection. To the best of our knowledge, the gastroprotective potential of SeNPs is unknown and also, a rapid preparation of orally stable SeNPs available for prospective commercial application in the clinic is needed. Thus, SeNPs-embedded chitosan microspheres (SeNPs-CM) were developed to deliver SeNPs, and their gastroprotective potential was evaluated. Results: Herein, a rapid, eco-friendly and economic preparation process, composed of synthesis of SeNPs decorated by chitosan (CS), purification of CS-SeNPs by ultra-filtration (UF) and spray-drying of the purified CS-SeNPs, was introduced to prepare SeNPs-CM. The uniformly distributed SeNPs with a nanosize range of 60 nm were loaded into CS-microspheres, and they could be released from the microspheres in gastric conditions. In addition, SeNPs-CM were safer than selenite in terms of Se dose, with a LD50 of around 8-fold of that of selenite, and it could efficiently enhance the Se retention in Se-deficient Wistar rats. Furthermore, SeNPs-CM pre-treatment might significantly attenuate the ethanol-induced gastric mucosal damage, based on histological evaluation. It might be partly attributed to the systematic antioxidant activities of SeNPs-CM, reflected by the reduction in lipid peroxidation, the augmentation in antioxidant enzymatic activity as well as decreasing aggressive nitric oxides (NO). Conclusion: SeNPs-CM could be taken into consideration as a prospective Se-supplement for the oral delivery of SeNPs, with prominent gastroprotective effect against ethanol-induced mucosal injury.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Mucosa Gástrica/efeitos dos fármacos , Microesferas , Nanopartículas/administração & dosagem , Selênio/farmacologia , Administração Oral , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Quitosana/química , Etanol/toxicidade , Mucosa Gástrica/metabolismo , Masculino , Nanopartículas/química , Ratos Wistar , Selênio/administração & dosagem , Selênio/química , Selênio/farmacocinética , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Ultrafiltração/métodos
6.
Clin Ther ; 42(3): 488-498.e8, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32046894

RESUMO

PURPOSE: Acid-suppressive medications are widely used in non-intensive care unit (non-ICU) patients for stress ulcer (SU) prophylaxis. However, SU prophylaxis in this population is still controversial. The purpose of this study was to systematically evaluate the efficacy and tolerability of these agents for SU prophylaxis in non-ICU patients. METHODS: Electronic databases including Cochrane, ClinicalTrials.gov, Ovid-Medline, Embase, Chinese CNKI, and Wanfang Data were systematically searched on July 10, 2019, for randomized controlled trials (RCTs) that evaluated acid-suppressive medications in non-ICU patients. Network meta-analysis and pairwise meta-analysis were performed to calculate odds ratios (ORs) and 95% CIs. A random-effects model was used for generating pooled estimates. The primary outcome was occurrence of SU bleeding, and the adverse drug events (ADEs) were described as the secondary outcome. FINDINGS: A total of 17 RCTs involving 1985 patients were eligible. Meta-analysis results indicated that the occurrence of SU bleeding was significantly decreased with all acid-suppressive medications compared with placebos (gastric mucosa protectants, OR = 0.29 [95% CI, 0.14-0.61]; H2-receptor antagonists, OR = 0.3 [95% CI, 0.18-0.50]; proton pump inhibitors [PPIs]: OR = 0.08 [95% CI, 0.04-0.16]). The occurrence of SU bleeding was significantly decreased with PPIs compared with gastric mucosa protectants (OR = 0.29; 95% CI, 0.12-0.72) and H2-receptor antagonists (OR = 0.28; 95% CI, 0.16-0.48). There was no significant difference between any 2 classes of PPIs on SU bleeding or any 2 acid-suppressive medications on ADEs. IMPLICATIONS: PPIs could significantly decrease SU bleeding risk without increasing ADEs than other acid-suppressive medications for SU prophylaxis in non-ICU patients. However, RCTs of high quality were required to confirm the findings of this investigation.


Assuntos
Antiácidos , Antagonistas dos Receptores Histamínicos H2 , Inibidores da Bomba de Prótons , Úlcera Gástrica , Antiácidos/efeitos adversos , Antiácidos/uso terapêutico , Antagonistas dos Receptores Histamínicos H2/efeitos adversos , Antagonistas dos Receptores Histamínicos H2/uso terapêutico , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle
7.
Food Funct ; 11(1): 662-679, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31895380

RESUMO

Our previous studies have demonstrated that the total triterpenes from the fruits of Chaenomeles speciosa (CSTT) exhibit effective therapeutic effects on gastric ulcer patients and animals. The present aim is to further investigate the mechanisms involved. The results indicated that CSTT could ameliorate IND-induced gastric injury, which was related to promoting IND-damaged GES-1 cell proliferation and migration, improving the IND-damaged rat GBF, ulcer area, inhibition rate and pathologic changes of gastric mucous tissue, increasing the amount of adhered gastric mucus, attenuating the volume and total acidity of the gastric effluents, and augmenting the gastric pH; further studies showed that CSTT obviously downregulated miR-423-5p mRNA, NAG-1 mRNA and protein expression, Bax, Bad, cytosol cytochrome C, Apaf-1, cleaved-caspase-3, and cleaved-caspase-9 protein expression and cytosol cytochrome C concentration, and upregulated TFF1, TFF2 and TFF3 mRNA and protein expression, Bcl-2, Bcl-xl, pro-caspase-3, and pro-caspase-9 protein expression, mitochondrial viability, mitochondrial cytochrome C concentration and Bcl-2/Bax, Bcl-xl/Bad ratios. These findings demonstrated that CSTT protected against IND-induced gastric damage by depressing miR-423-5p expression and modulating the TFF/NAG-1 pathway, which in turn restrained mitochondrion-mediated apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Fator 15 de Diferenciação de Crescimento/metabolismo , MicroRNAs/genética , Rosaceae/química , Úlcera Gástrica/tratamento farmacológico , Fator Trefoil-1/metabolismo , Triterpenos/administração & dosagem , Animais , Frutas/química , Fator 15 de Diferenciação de Crescimento/genética , Humanos , Indometacina/efeitos adversos , Masculino , MicroRNAs/metabolismo , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo , Úlcera Gástrica/fisiopatologia , Fator Trefoil-1/genética , Triterpenos/química
8.
Acta Biochim Biophys Sin (Shanghai) ; 52(1): 26-37, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31889181

RESUMO

Chlorine is shown to possess anti-gastric ulcer activity, since it can inactivate Helicobacter pylori, which is regarded as one of the most common risk factors for causing gastric problems. In the current study, the gastroprotective property of a novel dichloro-substituted Schiff base complex, 2, 2'- [-1, 2-cyclohexanediylbis(nitriloethylidyne)] bis(4-chlorophenol) (CNCP), against alcohol-induced gastric lesion in SD rats was assessed. SD rats were divided into four groups, i.e. normal, ulcer control, testing, and reference groups. Ulcer area, gastric wall mucus, and also gastric acidity of the animal stomachs were measured. In addition, antioxidant activity of CNCP was evaluated and its safe dose was identified. Immunohistochemistry staining was also carried to evaluate two important proteins, i.e. Bcl2-associated X protein (Bax) and heat shock protein 70 (HSP70). Moreover, the activities of super oxide dismutase and catalase, as well as the levels of prostaglandin E2 (PGE2) and malondialdehyde (MDA) were also measured. Antioxidant activity of CNCP was approved via the aforementioned experiments. Histological evaluations showed that the compound possesses stomach epithelial defense activity. Additionally, periodic acid-Schiff staining exhibited over-expression of HSP70 and down-expression of Bax protein in the CNCP-treated rats. Moreover, CNCP caused deceased MDA level and elevated PGE2 level, and at the same time increased the activities of the two enzymes.


Assuntos
Antioxidantes/uso terapêutico , Proteínas de Choque Térmico HSP70/metabolismo , Bases de Schiff/toxicidade , Bases de Schiff/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Proteína X Associada a bcl-2/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Clorofenóis/química , Dinoprostona/metabolismo , Modelos Animais de Doenças , Etanol/efeitos adversos , Etanol/farmacologia , Feminino , Fibroblastos/metabolismo , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Testes de Função Renal , Testes de Função Hepática , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Bases de Schiff/química , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
9.
Drug Dev Ind Pharm ; 46(2): 253-263, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31937139

RESUMO

Famotidine (FM) is considered among the first-line therapy for treatment of gastric ulcers; however, its poor aqueous solubility resulted in low bioavailability and limited therapeutic efficacy. Therefore, fast disintegrating tablet (FDT) incorporating FM solid dispersion was developed in a combined formulation approach for efficient treatment of ulcers. Within the investigated polymers, solid dispersions were prepared using the novel copolymer, Soluplus® (SP) by kneading and freeze-drying techniques at various FM:SP ratios. FM solid dispersion prepared at 1:10 ratio using freeze drying (FM-SP10) manifested the highest saturation solubility, having smooth porous surface with the complete conversion of FM to the amorphous form. FDTs of FM-SP10 was produced by direct compression using three ready-to-use excipients; F-melt, Pearlitol Flash, and Fujicalin. All tablets showed adequate thickness, diameter, weight variation, drug content, and friability (<1%). Fujicalin-FDTs (FM-FDT-FU) exhibited the shortest disintegration time with almost complete dissolution of the drug (>95%) within 30 min. It also revealed remarkable antiulcerogenic effect on ethanol induced gastric ulcers in terms of ulcer and protection indices compared to the market product. Pretreated rats with FM-FDT-FU demonstrated normal gastric area with the absence of edema and leucocytes infiltration, supported by the histological examination. FM-FDT-FU administration protected the stomach from oxidative damage and severe inflammatory response via the significant increase of glutathione level and the decreased levels of nitric oxide, interleukin and cyclooxygenase. Thus, the present study provides a promising dosage form of FM characterized by superior antiulcerogenic potential with desired tableting properties.


Assuntos
Famotidina/química , Famotidina/farmacologia , Polietilenoglicóis/química , Polivinil/química , Solubilidade/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Comprimidos/química , Comprimidos/farmacologia , Animais , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Excipientes/química , Inflamação/dietoterapia , Masculino , Polímeros/química , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos
10.
Eur J Med Chem ; 189: 112066, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982653

RESUMO

The current therapeutic demand focuses more on the discovery of safer NSAIDs rather than exploring more potent alternatives. The dual COX-2/5-LOX inhibition is a promising strategy for designing compounds with an enhanced efficacy, reduced side-effects and a broader anti-inflammatory spectrum in comparison to classical NSAIDs. In the present study, a hybridization strategy was adopted to combine the binding features of the non-selective COX inhibitor "sulindac" and the selective COX-2 inhibitor "celecoxib" which show 5-LOX inhibitory activity with that of licofelone and a celecoxib pyridone analogue which show dual COX-2/5-LOX inhibitory activity to design new series of pyrazole sulfonamide derivatives which, by design, should possess dual COX-2/5-LOX inhibitory activity. All the newly synthesized compounds were initially tested for their potential analgesic activity, then candidates that showed potential analgesic activity, were selected for the subsequent anti-inflammatory activity evaluation, as well as, ulcerogenicity testing. Moreover, in vitro assessment of their COX-1, COX-2 and 5-LOX inhibitory activities were performed. The benzothiophen-2-yl pyrazole carboxylic acid derivative 5b showed the most potent analgesic and anti-inflammatory activities surpassing that of celecoxib and indomethacin. It showed potent COX-1, COX-2 and 5-LOX inhibitory activity with IC50 of 5.40, 0.01 and 1.78 µM, respectively, showing a selectivity index of 344.56 that was much better than the used reference standards and its parent compounds, confirming its selectivity towards COX-2 over COX-1. The prodrug ester derivatives 6c and 6d showed equipotent activity to their parent compound 5b with no gastric ulcerogenicity. Molecular docking simulations confirmed that the newly synthesized compounds possess the structural features required for binding to the target enzymes COX-2 and 5-LOX.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antiulcerosos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Desenho de Fármacos , Inibidores de Lipoxigenase/farmacologia , Analgésicos/síntese química , Animais , Anti-Inflamatórios/síntese química , Antiulcerosos/síntese química , Araquidonato 5-Lipoxigenase/química , Ciclo-Oxigenase 1/química , Inibidores de Ciclo-Oxigenase 2/síntese química , Humanos , Inibidores de Lipoxigenase/síntese química , Masculino , Camundongos , Pirazóis/química , Ratos , Ratos Wistar , Úlcera Gástrica/tratamento farmacológico , Sulfonamidas/química
11.
Int J Mol Sci ; 21(3)2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31979417

RESUMO

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.


Assuntos
Antiulcerosos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Flavonoides/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Úlcera Gástrica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Ácido Acético/toxicidade , Animais , Antiulcerosos/farmacologia , Apoptose/genética , Caspase 3/metabolismo , Catalase/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Etanol/toxicidade , Flavonoides/farmacocinética , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Inflamação , Interleucina-10/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Oxirredução/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/enzimologia
12.
Nat Prod Res ; 34(4): 541-544, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30362366

RESUMO

The rhizomes of Bergenia ciliata (B. ciliata, Family: Saxifragaceae) are widely used for treating gastric ulcers in folk medicine in Asia. It was hypothesized that anti-ulcer activity of B. ciliata is due to its anti-Helicobacter pylori (H. pylori) activity. The anti-H. pylori activity was investigated on six clinical bacterial isolates using agar well-diffusion and broth micro-dilution methods. The anti-H. pylori activity of amoxicillin (standard) was the highest (Zone of inhibition; ZI = 25 mm, minimum inhibitory concentration; MIC=0.125 µg/µL) whereas among all the extracts of the rhizomes, methanol extract showed the highest activity (ZI = 16 mm, MIC = 12.50 µg/µL). Bioassay guided isolation of methanol extract using chromatographic and crystallization techniques isolated bergenin (ZI = 21mm, MIC = 0.391µg/µL) as constituent responsible for anti-H. pylori activity. The present study describes for the first time anti-H. pylori activity and possible mechanism of anti-ulcer properties of rhizomes of B. ciliata.


Assuntos
Benzopiranos/isolamento & purificação , Helicobacter pylori/efeitos dos fármacos , Rizoma , Saxifragaceae/química , Úlcera/tratamento farmacológico , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Ásia , Benzopiranos/uso terapêutico , Humanos , Medicina Tradicional , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Úlcera Gástrica/tratamento farmacológico
13.
J Enzyme Inhib Med Chem ; 35(1): 85-95, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31707866

RESUMO

To develop novel anti-inflammatory agents, a series of 5-alkyl-4-oxo-4,5-dihydro-[1, 2, 4]triazolo[4,3-a]quinoxaline-1-carboxamide derivatives were designed, synthesised, and evaluated for anti-inflammatory effects using RAW264.7 cells. Structures of the synthesised compounds were determined using 1H NMR, 13 C NMR, and HRMS. All the compounds were screened for anti-inflammatory activity based on their inhibitory effects against LPS-induced NO release. Among them, 5-(3,4,5-trimethoxybenzyl)-4-oxo-4,5-dihydro-[1, 2, 4]triazolo[4,3-a]quinoxaline-1-carboxamide (6p) showed the highest anti-inflammatory activity and inhibited NO release more potently than the lead compound D1. Further studies revealed that compound 6p reduced the levels of NO, TNF-α, and IL-6, and that its anti-inflammatory activity involves the inhibition of COX-2 and iNOS and downregulation of the mitogen-activated protein kinases (MAPK) signal pathway. Notably, compound 6p displayed more prominent anti-inflammatory activity than D1 and the positive control ibuprofen in the in vivo acute inflammatory model. Overall, these findings indicate that compound 6p is a therapeutic candidate for the treatment of inflammation.


Assuntos
Amidas/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Descoberta de Drogas , Quinoxalinas/farmacologia , Úlcera Gástrica/tratamento farmacológico , Amidas/síntese química , Amidas/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Quinoxalinas/síntese química , Quinoxalinas/química , Células RAW 264.7 , Ratos , Úlcera Gástrica/metabolismo , Relação Estrutura-Atividade
14.
J Ethnopharmacol ; 248: 112297, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31606535

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Members of the genus Erythrina have been traditionally used in the treatment of various ailments such as inflammation and gastrointestinal disorders. Erythrina speciosa (Fabaceae) is a spiny, deciduous shrub or small tree native to Southern America in Brazil. It is cultivated in Africa and Asia. The traditional usage of E. speciosa indicated its antibacterial, analgesic, and anti-inflammatory activities. AIM OF THE STUDY: Evaluation of the phytochemical constituents, gastroprotective effects and possible mechanism of action of the ethyl acetate fraction obtained from the methanol extract of E. speciosa leaves (ESLE). MATERIALS AND METHODS: Chemical characterization of ESLE was done using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). The gastroprotective activity of ESLE was evaluated using ethanol-induced gastric-ulcer model in rats. Rats were pre-treated with ESLE 25, 50 and 100 mg/kg 1 h before the administration of absolute ethanol. Histological analysis, mucin content, and total acidity were evaluated. The possible mechanism of action of ESLE was studied through the examination of oxidative stress and inflammatory markers, PGE2, and NF-κB, iNOS, COX-2, and HSP-70 immunoexpression. In vitro, anti-Helicobacter pylori activity of ESLE was also studied using micro-well dilution method. RESULTS: Fourteen compounds were tentatively identified including alkaloids, flavonoids, and saponins. ESLE exerted a powerful gastroprotective effect. The pre-treatment with ESLE at different doses resulted in a significant reduction in gastric lesions and significant elevation in the mucin production. These effects could be partially mediated by the potent anti-inflammatory activity of ESLE as evidenced by the significant reduction in the immunoexpression of NF-κB, COX-2, iNOS and the reduction in the pro-inflammatory marker, TNF-α. ESLE counteracted the ethanol-induced oxidative stress by increasing the levels of depleted GSH and catalase as well as significantly attenuating the ethanol-induced lipid peroxidation tissue levels. In addition, ESLE exhibited in vitro antibacterial activity against H. pylori. CONCLUSIONS: The chemical constituents of ESLE strongly support its potent gastroprotective effect suggesting its future potential application in the management of gastric ulcer by eliminating its symptoms and causes including H. pylori.


Assuntos
Antiulcerosos/uso terapêutico , Fabaceae , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/farmacologia , Ciclo-Oxigenase 2/metabolismo , Egito , Etanol , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Masculino , Mucinas/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
15.
Eur J Pharm Sci ; 143: 105204, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31870812

RESUMO

Liquid raft-forming formulations comprising solid dispersions of glycoside-rich Centella asiatica extract and Eudragit® EPO (GR-SD) were developed to achieve prolonged delivery of the glycosides, asiaticoside (AS) and madecassoside (MS) in the stomach and thus increase the effectiveness of gastric ulcer treatment. Solid dispersions of GR extract and Eudragit® EPO (GR-SD, weight ratio 1:0.5) resulted in the highest solubility of AS (41.7 mg/mL) and MS (29.3 mg/mL) and completed dissolution of both glycosides occurred in SGF within 10 min. The optimized raft-forming formulation was composed of alginate (2%), HPMC K-100 (0.5%), GR-SD (1.2%), and calcium carbonate (0.5%) as a calcium source and carbon dioxide producer. The formulation provided sufficient raft strength (> 7.0 g), rapid floating behavior in SGF (~30 s), and sustained release of AS (more than 80%) and MS (85%) over 8 h. GR-SD-based formulations administered once daily to rats for two days at a dose of 10 mg AS/kg reduced the severity of gastric ulcer induced by indomethacin with a greater curative efficacy than those of unformulated GR extract and a standard antiulcer agent: lansoprazole (p < 0.05). These findings demonstrate that GR-SD-based raft-forming systems offer significant promise for improving the treatment of gastric ulcers induced by non-steroidal anti-inflammatory drugs.


Assuntos
Antiulcerosos/administração & dosagem , Sistemas de Liberação de Medicamentos , Ácidos Polimetacrílicos/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Triterpenos/administração & dosagem , Animais , Antiulcerosos/química , Liberação Controlada de Fármacos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Indometacina , Masculino , Ácidos Polimetacrílicos/química , Ratos Wistar , Solubilidade , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Triterpenos/química
16.
Oxid Med Cell Longev ; 2019: 1983137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827669

RESUMO

Ethnomedicinal studies in the Amazon community and in the Northeast region of Brazil highlight the use of Libidibia ferrea fruits for the treatment of gastric problems. However, there are no data in the literature of this pharmacological activity. Thus, the aim of this paper is to provide a scientific basis for the use of the dry extract of L. ferrea pods (DELfp) for the treatment of peptic ulcers. Phytochemical characterization was performed by HPLC/MS. In vitro antioxidant activity was assessed using DPPH, ABTS, phosphomolybdenum, and superoxide radical scavenging activity. The gastroprotective activity, the ability to stimulate mucus production, the antisecretory activity, and the influence of -SH and NO compounds on the antiulcerogenic activity of DELfp were evaluated. The healing activity was determined by the acetic acid-induced chronic ulcer model. Anti-Helicobacter pylori activity was investigated. HPLC/MS results identified the presence of phenolic compounds, gallic acid and ellagic acid, in DELfp. The extract showed antioxidant activity in vitro. In ulcers induced by absolute ethanol and acidified ethanol, the ED50 values of DELfp were 113 and 185.7 mg/kg, respectively. DELfp (100, 200, and 400 mg/kg) inhibited indomethacin-induced lesions by 66.7, 69.6, and 65.8%, respectively. DELfp (200 mg/kg) reduced gastric secretion and H+ concentration in the gastric contents and showed to be independent of nitric oxide (NO) and dependent on sulfhydryl (-SH) compounds in the protection of the gastric mucosa. In the chronic ulcer model, DELfp reduced the area of the gastric lesion. DELfp also showed anti-H. pylori activity. In conclusion, DELfp showed antioxidant, gastroprotective, healing, and antiulcerogenic activities. The mechanism of these actions seems to be mediated by different pathways and involves the reduction of gastric secretion and H+ concentration, dependence on sulfhydryl compounds, and anti-H. pylori activity. All these actions support the medicinal use of this species in the management of peptic ulcers.


Assuntos
Antiulcerosos/química , Antioxidantes/química , Fabaceae/química , Extratos Vegetais/química , Ácido Acético/toxicidade , Animais , Antiulcerosos/farmacologia , Antiulcerosos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Fabaceae/metabolismo , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Helicobacter pylori/efeitos dos fármacos , Espectrometria de Massas , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Fenóis/análise , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Compostos de Sulfidrila/química , Compostos de Sulfidrila/metabolismo
17.
Nutrients ; 11(12)2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31847337

RESUMO

We investigated the effects of enteral nutrition formula on non-steroidal anti-inflammatory drug (NSAID)-induced gastric lesions in mice. Male ICR mice aged 7-9 weeks old were fasted, then orally given either purified water, Mermed® One, or 2-fold diluted Terumeal® 2.0α as enteral nutrition (25 or 50 mL/kg each). Indomethacin (IND) was orally administered at 20 mg/kg after 30 min, and the stomach was removed 6 h later and fixed in formalin. The number and area of lesions in the stomachs of the mice given enteral nutrition showed a significant, dose-dependent decrease compared to the purified water-treated group, and no significant difference was seen between the two enteral nutrition-treated groups. Comparable time courses of plasma IND concentrations suggest that enteral nutrition does not inhibit gastrointestinal absorption of IND. Our findings indicate that administering enteral nutrition could inhibit the onset of NSAID-induced gastric ulcers.


Assuntos
Nutrição Enteral , Alimentos Formulados , Indometacina/toxicidade , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Úlcera Gástrica/patologia
18.
Biomed Res Int ; 2019: 4921086, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31886219

RESUMO

This study aims to delineate the effects of Manilkara zapota Linn. (Sapodilla) fruit chloroform (Mz.CHCl3) and aqueous (Mz.Aq) extracts tested through different techniques. Antidiarrheal activity and intestinal fluid accumulation were examined by using castor oil-induced diarrhea and castor oil fluid accumulation models. Isolated rabbit jejunum tissues were employed for in vitro experiments. Antimotility and antiulcer were performed through charcoal meal transient time and ethanol-induced ulcer assay, molecular studies were conducted through proteomic analysis, and virtual screening was performed by using a discovery studio visualizer (DSV). Mz.CHCl3 and Mz.Aq extracts attributed dose-dependent (50-300 mg/kg) protection (20-100%) against castor oil-induced diarrhea and dose-dependently (50-300 mg/kg) inhibited intestinal fluid secretions in mice. Mz.CHCl3 and Mz.Aq extracts produce relaxation of spontaneous and K+ (80 Mm) induced contractions in isolated tissue preparations and decreased the distance moved by charcoal in the gastrointestinal transit model in rats. It showed gastroprotective effect in ulcerative stomach of rats and decreased levels of IL-18 quantified by proteomic analysis. Histopathological results showed ethanol-induced significant gastric injury, leading to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all gastric zones using hematoxylin and eosin (H&E) staining. Moreover, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), cyclooxygenase (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFκB). In silico results were comparative to in vitro results evaluated through virtual screening. Moreover, ethanol increased the activation and expression of tumor necrotic factor, cyclooxygenase, and nuclear factor kappa-light-chain-enhancer of activated B cells. This study exhibits the gastroprotective effect of Manilkara zapota extracts in the peritoneal cavity using a proteomic and in silico approach which reveals different energy values against target proteins, which mediate the gastrointestinal functions.


Assuntos
Antidiarreicos , Diarreia , Regulação da Expressão Gênica/efeitos dos fármacos , Manilkara/química , Extratos Vegetais , Proteoma/biossíntese , Proteômica , Úlcera Gástrica , Animais , Antidiarreicos/química , Antidiarreicos/farmacologia , Óleo de Rícino/efeitos adversos , Óleo de Rícino/farmacologia , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/metabolismo , Diarreia/patologia , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Coelhos , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
19.
Klin Lab Diagn ; 64(11): 669-672, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31747495

RESUMO

There was reported the results of the use of recombinant interleukin-1ß in basic conservative measures in the surgical treatment of acute gastroduodenal ulcer bleeding. Gastric ulcer were in 20 patients, duodenal ulcer in 84 patients and combined ulcers in 16 patients. According to А.А. Шалимов hospitalized patients with mild blood loss were 27, moderate degree - 62 and severe degree - 31 patients. According to J. Forrest, 29 showed active bleeding (F Ia, F Ib), in 67 - unstable hemostasis (F IIa, F IIb, F IIc) and in 24 - F III. Within the framework of differentiated individual-active tactics, patients were operated in emergency (21), urgent (38), delayed (35), and 26 people underwent early planned operations. Patients in the main group (63) after the operation, was included recombinant interleukin-1ß to the basic therapeutic measures additionally, taking into account the degree of blood loss and immune disorders. Patients of comparison group (57) before and after surgery received standard basic therapy without immunocorrection. In a comparative aspect, it has been proved that in postoperative period on the background of standard conservative measures, the use of recombinant interleukin-1ß positively influences elimination of the secondary immunodeficiency and cytokine imbalance significantly improves the results of surgical treatment.


Assuntos
Úlcera Duodenal/cirurgia , Interleucina-1beta/uso terapêutico , Úlcera Gástrica/cirurgia , Úlcera Duodenal/tratamento farmacológico , Humanos , Período Pós-Operatório , Proteínas Recombinantes/uso terapêutico , Úlcera Gástrica/tratamento farmacológico
20.
World J Gastroenterol ; 25(42): 6342-6353, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31754294

RESUMO

BACKGROUND: The two main causes of gastric ulcer bleeding are Helicobacter pylori (H. pylori) infection and ulcerogenic medicines, although the number of cases caused by each may vary with age. In Japan, the rate of H. pylori infection has fallen over the last decade and the number of prescriptions for non-steroidal anti-inflammatory drugs (NSAIDs) and antithrombotic drugs is increasing as the population ages. Methods of treatment for gastric ulcer bleeding have advanced with the advent of hemostatic forceps and potassium-competitive acid blocker (P-CAB). Thus, causes and treatments for gastric ulcer bleeding have changed over the last decade. AIM: To examine the trends of gastric ulcer bleeding over 10 years in the metropolitan area of Japan. METHODS: This is a single-center retrospective study. A total of 564 patients were enrolled from inpatients admitted to our hospital with gastric ulcer bleeding between 2006 and 2016. Age, medication history, H. pylori infection, method of treatment, rate of rebleeding, and the length of hospitalization were analyzed. Factors associated with gastric ulcer bleeding were evaluated using Fisher's exact test, Pearson's Chi-squared test or Student's t-test as appropriate. The Jonckheere-Terpstra test was used to evaluate trends. A per-protocol analysis was used to examine the rate of H. pylori infection. RESULTS: There was a significant increase in the mean age over time (P < 0.01). The rate of H. pylori infection tended to decrease over the study period (P = 0.10), whereas the proportion of patients taking antithrombotic agents or NSAIDs tended to increase (P = 0.07). Over time, the use of NSAIDs and antithrombotic drugs increased with age. By contrast, the rate of H. pylori infection during the study period fell with age. H. pylori-induced ulcers accounted for the majority of cases in younger patients (< 70 years old); however, the rate decreased with age (P < 0.01). The method of treatment trend has changed significantly over time. The main method of endoscopic hemostasis has changed from clipping and injection to forceps coagulation (P < 0.01), and frequently prescribed medicines have changed from proton pump inhibitor to P-CAB (P < 0.01). The rate of rebleeding during the latter half of the study was significantly lower than that in the first half. CONCLUSION: These trends, gastric ulcers caused by ulcerogenic drugs were increasing with age and H. pylori-induced ulcers were more common in younger patients, were observed.


Assuntos
Hemorragia Gastrointestinal/tratamento farmacológico , Hemorragia Gastrointestinal/epidemiologia , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Úlcera Gástrica/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Anti-Inflamatórios não Esteroides/uso terapêutico , Cidades , Feminino , Helicobacter pylori , Técnicas Hemostáticas , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Potássio/química , Estudos Retrospectivos , Úlcera Gástrica/tratamento farmacológico
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