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1.
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
2.
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
3.
Intern Med ; 58(19): 2759-2766, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582592

RESUMO

objective In patients continuing antithrombotics, delayed bleeding after gastric endoscopic submucosal dissection (ESD) is a severe complication. Vonoprazan (VPZ) exerts a rapid, potent, and long-lasting antacid effect compared with traditional proton-pump inhibitors (PPIs). This study aimed to compare the incidence of delayed bleeding after gastric ESD between the use of VPZ and PPIs in patients continuing antithrombotics. Methods In this retrospective analysis, we examined 71 patients with 101 lesions treated with traditional PPIs (PPI group) and 59 patients with 90 lesions treated with VPZ (VPZ group). After 2 days (day 0 and 1) of intravenous PPI administration, either an oral PPI or VPZ was administered from postoperative day 2 to 8 weeks after ESD. We assessed the incidence of overall delayed bleeding as well as bleeding that occurred from day 2 until 8 weeks after ESD. Results There was no significant difference in the use of antithrombotic agents between the groups. Overall delayed bleeding occurred 13 times (18%) in 9 patients in the PPI group and 18 times (31%) in 17 patients in the VPZ group (p=0.10). Bleeding from day 2 until 8 weeks after ESD occurred 12 times (17%) in 9 patients in the PPI group and 8 times (14%) in 8 patients in the VPZ group. Conclusion Even with a potent antacid agent, such as VPZ, the incidence of delayed bleeding was high in patients undergoing ESD with continuous antithrombotic agents.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Fibrinolíticos/efeitos adversos , Hemorragia Pós-Operatória/etiologia , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/uso terapêutico , Feminino , Humanos , Masculino , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis , Estudos Retrospectivos , Úlcera Gástrica/tratamento farmacológico , Sulfonamidas , Fatores de Tempo
4.
Schweiz Arch Tierheilkd ; 161(9): 523-531, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488393

RESUMO

INTRODUCTION: This study involved 60 cows aged 1.9 to 13 years (mean 4.8 ± 2.3 years) with type-3 abomasal ulcer. The most common clinical signs were, in decreasing order of frequency, partial or complete anorexia (98%), obtunded demeanour (95%), decreased skin surface temperature (78%), congested scleral vessels (73%), abdominal guarding (61%), tachypnoea (58%), fever (58%) and tachycardia (55%). One or more concomitant disorders were diagnosed in 86% of the cows. The most common abnormal laboratory findings were hypokalaemia (75%), shortened glutaraldehyde test time (46%) and hyperfibrinogenaemia (43%). The diagnosis of type-3 abomasal ulcer was made in all cows during laparotomy and/or at postmortem examination. Forty-eight (80%) cows were euthanased immediately after the initial examination, during laparotomy or after unsuccessful treatment. Twelve (20%) cows were treated with a solution of sodium chloride and glucose administered via an indwelling jugular catheter, antibiotics, metamizole or flunixin, and discharged from the clinic. Ten cows were still in production two years later.


Assuntos
Abomaso/patologia , Úlcera Gástrica/veterinária , Animais , Antibacterianos/uso terapêutico , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/tratamento farmacológico , Feminino , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/tratamento farmacológico
5.
Int J Nanomedicine ; 14: 4911-4929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456637

RESUMO

Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.


Assuntos
Acetofenonas/administração & dosagem , Acetofenonas/farmacologia , Quitosana/química , Mucosa Gástrica/efeitos dos fármacos , Nanopartículas/química , Oligossacarídeos/química , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/farmacologia , Acetofenonas/uso terapêutico , Administração através da Mucosa , Animais , Biomarcadores/metabolismo , Varredura Diferencial de Calorimetria , Ciclo-Oxigenase 2/metabolismo , Liberação Controlada de Fármacos , Cinética , Masculino , Nanopartículas/ultraestrutura , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Suínos , Difração de Raios X
6.
BMC Complement Altern Med ; 19(1): 205, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391093

RESUMO

BACKGROUND: Gastric ulcer is one of the most prevalent diseases worldwide. In Iranian folk medicine, Achillea wilhelmsii (AW) is used as a treatment for gastric ulcer. Previous reports also mentioned Antiulcerogenic properties for this herbal plant. This study investigated the therapeutic effects of Achillea wilhelmsii C. Koch extract on indomethacin-induced gastric lesion in rats, from both proteomic and metabolomic perspectives. METHODS: The rats were divided into 4 groups. Gastric ulceration was induced by a single dose of indomethacin (45 mg/kg) by oral gavage. An amount of 800 mg/kg of AW extract was administered orally. Serum and tissue samples were collected for further investigations. The metabolomic study was performed by 1H-NMR CPMG spectrometry. Proteomic analysis was also executed by using two dimensional gel electrophoresis (2DE) followed by liquid chromatography coupled to tandem mass spectrometry (LC-ESI/MS/MS). Real time PCR was used to confirm some of the genes. RESULTS: The macroscopic and microscopic investigations confirmed the effectiveness of the AW extract. There was a panel of metabolites which showed alteration during gastric lesion development. The levels of some of these metabolite reversed nearly to their control values after the administration of AW extract. There were also changes in the levels of some proteins including Alb, Fabp5, Hspb1, Tagln, Lgals7, Csta and Myl9 which were reversed after AW administration. CONCLUSIONS: Our findings suggested that Achillea wilhelmsii C. Koch extract could be a potential therapy to be used for indomethacin-induced gastric lesion treatment in the future. However, further investigations are needed to confirm the results.


Assuntos
Achillea/química , Antiulcerosos/administração & dosagem , Extratos Vegetais/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/isolamento & purificação , Humanos , Indometacina/efeitos adversos , Masculino , Metabolômica , Extratos Vegetais/isolamento & purificação , Proteômica , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/genética , Úlcera Gástrica/metabolismo
7.
Biol Pharm Bull ; 42(7): 1120-1127, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257288

RESUMO

Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1ß, resulting in reduced nitric oxide and prostaglandin E2 production. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Edema/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Úlcera Gástrica/tratamento farmacológico , Estômago/efeitos dos fármacos , Animais , Aspirina , Carragenina , Celecoxib , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Indometacina , Masculino , Olea , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Ratos Sprague-Dawley , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo
8.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2338-2347, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359661

RESUMO

The aim of this paper was to observe the combination therapy with total triterpenoids of Chaenomeles speciosa and omeprazole on indomethacin-induced gastric ulcer in rats, and explore its possible mechanism. Rats were randomly divided into normal group, model group, omeprazole monotherapy(3.6 mg·kg~(-1)) group, total triterpenoids of C. speciosa monotherapy(100 mg·kg~(-1)) group, total triterpenoids of C. speciosa and omeprazole combination therapy(100 mg·kg~(-1)+3.6 mg·kg~(-1)) group. Except for the normal group, the other groups were given indomethacin(20 mg·kg~(-1)) by oral once a day for 7 consecutive days. Then the treated groups were given corresponding drugs by gavage, once a day for 14 consecutive days. The next day after the last administration, half of the rats in each group were measured the gastric mucosal blood flow, gastric juice volume and serum TNF-α, IL-1ß, IL-6, IL-4 and IL-10. After the remaining rats in each group were underwent pyloric ligation 4 hours after the last administration, the gastric endocrine volume, pH value and total acidity of gastric secretion were measured, then histological analysis was performed, MPO activity, cAMP content and histomorphological analysis were conducted. Real-time PCR was applied to detect the mRNA expressions of gastric tissue TNF-α,IL-1ß, IL-6, IL-4, IL-10, VEGFA, A_(2A)R; the protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue were detected by Western blot. The results indicated that total triterpenoids of C. speciosa and omeprazole combination therapy might significantly increase gastric mucosal blood flow, gastric mucus volume, reduce gastric endocrine volume, secretion acidity and mucosal damage, decrease the levels of TNF-α,IL-1ß and IL-6, increase the levels of IL-4 and IL-10 in blood and gastric tissue, inhibit the activity of MPO, increase the content of cAMP in gastric tissue, up-regulate the mRNA expressions of VEGFA, A_(2A)R and protein expressions of VEGFA, A_(2A)R, PKA, p-PKA, CREB, p-CREB, EGF, EGFR, p-EGFR, MUC6, TFF2 in gastric tissue, elevate p-PKA/PKA, p-CREB/CREB and p-EFGR/EFGR. Moreover, the combination therapy with total triterpenoids of C. speciosa and omeprazole was more obvious than those of two monotherapies. These aforementioned findings suggested that the combination therapy with total triterpenoids of C. speciosa and omeprazole on indomethacin-induced gastric ulcer have significant therapeutic effect on indomethacin induced gastric ulcer in rats, its mechanism might be related to regulating A_(2A)R/AKT/CREB, A_(2A)R/VEGFA, EGF/EGFR and MUC6/TFF2 signaling pathways, inhibiting pro-inflammatory factors, increasing gastric mucosal blood flow, up-regulating mucosal cell proliferation factors and promoting mucosal protective factors.


Assuntos
Omeprazol/farmacologia , Rosaceae/química , Úlcera Gástrica/tratamento farmacológico , Triterpenos/farmacologia , Animais , Citocinas , Mucosa Gástrica , Indometacina , Compostos Fitoquímicos/farmacologia , Distribuição Aleatória , Ratos , Úlcera Gástrica/induzido quimicamente , Fator de Necrose Tumoral alfa
9.
J Ethnopharmacol ; 241: 112023, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31195031

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Woodfordia fruticosa is traditionally used in the Ayurvedic system of medicine for the treatment of diarrhoea, poisoning, menstrual disorders, ulcers and fertility. In the present study, we report a standardized extract preparation through modern scientific approach for anti-ulcer activity. MATERIALS AND METHODS: The hydro-alcoholic extract of flowers of W. fruticosa was standardized using four chemical markers. The standardized extract was coded as ICB014. HPLC method was developed for identification and quantification of Gallic Acid, Oenothein-C, Quercetin and Kaempferol. Based on the prior published H+, K+-ATPase activity and Anti-bacterial activity against Helicobacter pylori of ICB014, was evaluated for its in-vivo efficacy in gastric ulcers models in rats followed by regulatory safety studies. RESULTS: The extract demonstrated efficacy at 31.25-62.5 mg/kg in gastric ulcer models. The extract was safe by oral route up to 2000 mg/kg in a single dose and NOAEL of 800 mg/kg in 28 days repeat study. Bioequivalent capsule formulation was prepared. CONCLUSIONS: The extract showed anti-ulcer potential and is ready for clinical evaluation.


Assuntos
Antiulcerosos/uso terapêutico , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Woodfordia , Animais , Antiulcerosos/farmacocinética , Antiulcerosos/toxicidade , Etanol , Feminino , Flores , Helicobacter pylori/efeitos dos fármacos , Ácido Clorídrico , Masculino , Camundongos , Fitoterapia , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Testes de Toxicidade
10.
Food Chem Toxicol ; 131: 110539, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158404

RESUMO

The chemical characterization and protective role against ethanol-induced gastric ulcerated rats of a polysaccharide fraction from Bletilla striata (BSP) collected by ultrafiltration membrane approach were evaluated. This BSP faction was consisted of mannose and glucose at a molar ratio of 2.4:1 approximately, with a molecular weight of 146 KDa. FT-IR, NMR and XRD spectra indicated that BSP faction contained α-Man and ß-Glc residues with low overall crystallinity. The polysaccharide exhibited significant scavenging activities of ABTS and FRAP, as well as non-toxicity against human gastric epithelial GES-1 cells. Oral administration with 100 mg/kg of BSP for 3 days continuously could significantly prevent the formation of ethanol-induced gastric mucosal lesion. It could also reduce the levels of pro-inflammatory cytokines, including TNF-α, IL-1ß, IL-6, and IL-18, and MPO activity in gastric tissue. Additionally, the BSP faction exhibited antioxidant activity, increased the content of PEG2 as a defensive factor, and suppressed MAPK/NF-κB signaling pathway in gastric tissue. These results indicated that the gastroprotective activity of BSP faction could be attributed to the reduction of pro-inflammatory cytokines and oxidative stress and the inhibition of MAPK/NF-κB pathways. Our results provided substantial evidence that BSP could be a promising phytomedicine for gastric ulcer prevention.


Assuntos
Fármacos Gastrointestinais/farmacologia , Orchidaceae/química , Polissacarídeos/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Linhagem Celular , Citocinas/metabolismo , Dinoprostona/metabolismo , Etanol , Depuradores de Radicais Livres/isolamento & purificação , Depuradores de Radicais Livres/farmacologia , Depuradores de Radicais Livres/toxicidade , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Humanos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Polissacarídeos/isolamento & purificação , Polissacarídeos/toxicidade , Ratos , Transdução de Sinais/efeitos dos fármacos , Úlcera Gástrica/induzido quimicamente , Superóxido Dismutase/metabolismo
11.
Arch Pharm (Weinheim) ; 352(7): e1800339, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31231875

RESUMO

Ketoprofen belongs to one of the most common nonsteroidal anti-inflammatory drugs (NSAIDs) but its clinical usefulness has been restricted due to the high incidence of gastrointestinal complications. The release of reactive oxygen species (ROS) in NSAIDs therapy plays a major role in causing gastric complications. Antioxidants not only prevent gastric ulceration and lipid peroxidation but also preserve glutathione-type peroxidase (GPO) activity. Therefore, the present study investigates the utility of combining anti-inflammatory and antioxidant properties of two different compounds in a single molecule to form a series of 16 ketoprofen-antioxidant mutual codrugs. The free carboxylic group, which is believed to be one of the reasons for gastric toxicity of ketoprofen, was masked temporarily by simple and double esterification with alcoholic/phenolic-OH of natural antioxidants. In simple esterification, ketoprofen is directly linked to natural antioxidants (IIa-h) in the hope to obtain drugs free of gastric side effects. In an attempt to improve the in vivo lability, as well as gastric side effects, the double ester codrugs, that is, ketoprofen-antioxidant through the glycolic acid spacer (-CH2 COO; IIIa-h), have also been designed and synthesized. The synthesized codrugs were characterized by IR, 1 H NMR, 13 C NMR, mass spectroscopy and elemental analysis. The in vitro hydrolysis studies showed the lowest hydrolysis (highest stability) in acidic pH 1.2, whereas moderate hydrolysis was seen at pH 7.4 and significant hydrolysis in 80% human blood plasma, as indicated by their t1/2 . The pharmacological evaluation results indicate that these ketoprofen-antioxidant mutual codrugs showed the retention of anti-inflammatory and analgesic activity with a significant reduction in the ulcer index.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antiulcerosos/farmacologia , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Cetoprofeno/farmacologia , Analgésicos/síntese química , Analgésicos/química , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antiulcerosos/síntese química , Antiulcerosos/química , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , Humanos , Hidrólise , Cetoprofeno/química , Cinética , Estrutura Molecular , Dor/tratamento farmacológico , Picratos/antagonistas & inibidores , Ratos , Úlcera Gástrica/tratamento farmacológico
12.
Food Funct ; 10(7): 3965-3976, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31204764

RESUMO

The dry root of Hedysarum polybotrys Hand.-Mazz., commonly known as "Hong Qi", has a variety of health benefits. The present study was undertaken to explore the anti-gastric ulcer potential effect of Hedysarum polysaccharides (HPS; HPS-50, HPS-80), the principal active fraction of Radix Hedysari (RH). The anti-gastric ulcer effects of HPS were evaluated using an animal model of ulcerative lesions induced by acetic acid. The effects of antioxidant factors, anti-inflammatory cytokines, and mucosal blood flow regulatory factor levels in the gastric tissue homogenate of rats were analyzed for the bioactivities of HPS. The results showed that, compared with the acetic acid-induced ulcerated group, the ulcer inhibition rate of HPS-treated rats was significantly increased. The pathological findings suggested that mucosal regeneration, cell migration, and inflammatory cell infiltration were decreased, and collagen fibers were significantly reduced. Extensive granulation tissue proliferation indicated the healing stage was initiated, suggesting a good prognosis. The oxidative stress status of the gastric ulcer rats was improved, the levels of TNF-α and IL-6 were significantly decreased, and the levels of PGE-2 and NO were increased (P < 0.05). HPS-80-H may be a promising ingredient for incorporation into functional foods or nutritional supplements for the prevention of gastric ulcers.


Assuntos
Ácido Acético/efeitos adversos , Antiulcerosos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Polissacarídeos/farmacologia , Ranunculaceae/química , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Interleucina-6/metabolismo , Masculino , Membrana Mucosa/efeitos dos fármacos , Estresse Oxidativo , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Estômago/efeitos dos fármacos , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Fator de Necrose Tumoral alfa/metabolismo , Cicatrização/efeitos dos fármacos
13.
An Acad Bras Cienc ; 91(2): e20181044, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241706

RESUMO

Myristica fragrans seeds are traditionally used to treat dyspepsia, vomiting and abdominal pain. The purpose of this study was to investigate the protective effect of Myristica fragrans in ethanol induced gastric ulcer. Study was carried out on rats, divided into four groups; negative control, positive control, standard drug control, and Myristica fragrans extract treated rats. The pH, ulcer index, acidity values and histopathological examination of stomach were evaluated. Myristica fragrans significantly (P<0.05) reduced gastric lesions by 41.68% in ethanol induced ulcer model at 200 mg/kg when compared to sucralfate (60.41%). However, histopathological findings appeared similar in Myristica fragrans extract treated and standard drug control groups, where stomachs were found with mild erosion of superficial epithelium and few infiltrated inflammatory cells. pH of gastric contents of rats from extract treated was increased (4.25 ± 0.25) as compared to positive control group (2.25 ± 0.25). Ulcer index of extract treated rats was improved (41.74%). Moreover, total acidity of extract treated group (60.0 ± 0.47) was decreased as compared to control group (74.50 ± 1.04). It is concluded that Myristica fragrans showed significant protecting activity in ethanol induced ulcer. Isolation and purification of phytochemicals responsible for gastroprotective activity becomes necessary.


Assuntos
Antiulcerosos/uso terapêutico , Myristica/química , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/isolamento & purificação , Modelos Animais de Doenças , Etanol , Masculino , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Ratos , Ratos Wistar , Sementes , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
14.
J Ethnopharmacol ; 239: 111931, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31055003

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Balanites aegyptiaca L. Delile (Zygophyllaceae) is a perennial tree that is mostly found in Africa, south Asia and most desert environments. Decoctions of its stem barks are used in northern Nigeria for the treatment of ulcers and stomach issues. Other folkloric uses include treatment of wounds, malaria, dysentery, asthma, and fever. AIM OF THE STUDY: The present study evaluated the antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca in Wistar rats. MATERIALS AND METHODS: The antiulcer activity of the aqueous stem bark extract of Balanites aegyptiaca (125, 250 and 500 mg/kg, p.o.) was evaluated in ethanol, indomethacin, pylorus ligation and acetic acid-induced ulcer models in rats. Parameters such as mean ulcer indices and percentage ulcer inhibition were assessed in ethanol, indomethacin and acetic acid-induced ulcer models while gastric volume, pH, and titratable acidity were evaluated in the pylorus ligation ulcer model. RESULTS: The extract at the doses of 125, 250 and 500 mg/kg caused a significant (p < 0.01), dose dependent reduction in mean ulcer indices in the ethanol and indomethacin ulcer models. A significant dose dependent reduction in mean ulcer indices were also observed after three (p < 0.01) and seven (p < 0.001) days of treatment with the extract in acetic acid-induced ulcer model. In pylorus ligation model, the gastric secretion parameters (gastric volume, pH, and titratable acidity) showed no alteration in the different doses of the extract when compared to the control. CONCLUSION: Our study showed that the aqueous stem bark extract of Balanites aegyptiaca possesses gastroprotective and ulcer healing properties and therefore not only provides scientific evidence for its folkloric use in the treatment of ulcers but also showed evidence that it may be used in the development of a new phytotherapeutic formulation for the treatment of peptic ulcer.


Assuntos
Antiulcerosos/uso terapêutico , Balanites , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Ácido Acético , Animais , Etanol , Indometacina , Ligadura , Masculino , Fitoterapia , Casca de Planta , Caules de Planta , Piloro/cirurgia , Ratos Wistar , Úlcera Gástrica/induzido quimicamente
15.
Biomed Res Int ; 2019: 4605748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31111054

RESUMO

Background and Aims: Hydrotalcite plays an important role in the therapy of gastric ulcer induced by nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about the mechanism. We designed two experiments to study the preventive and curative effects of hydrotalcite on NSAIDs-related gastric injury in rats and to investigate the relationship between the protective and curative mechanism of hydrotalcite and the secretion of epidermal growth factor (EGF)/prostaglandin E2 (PGE2). Methods: Two experiments were separately designed to evaluate the preventive and curative effects of hydrotalcite. A total of 25 male rats and 25 female rats were randomly divided into five groups (vehicle group, model group, omeprazole group, hydrotalcite group, and ranitidine group) in each experiment. Rats were treated with indomethacin by gavage to build the model of acute gastric mucosal injury. The concentrations of EGF and PGE2 in blood specimens and mucosal injury indexes by gross inspection were measured and an immunohistochemical technique was also employed to test the levels of EGF, cyclooxygenase-1 (COX-1), and cyclooxygenase-2 (COX-2) in gastric mucosa. Results: Comparing with model group in both preventive and curative experiments, hydrotalcite decreased the gastric injury in the mucosa of stomach significantly (7±4.5 vs. 16±11.25, 1.5±2 vs. 2.5±6; P<0.01, P<0.05). The levels of EGF and PGE2 in blood serum were markedly higher in hydrotalcite group than that in model group and ranitidine group in preventive experiment (574.39±34.28 vs. 486.22±41.73, 488.07±24.44; P<0.01, P<0.01). The expression levels of COX-2 in gastric mucosa were also higher in hydrotalcite group than that in model group in both preventive and therapeutic experiments (12±4 vs. 9±6, 14±7 vs. 9±4; P<0.01, P<0.05). Conclusions: Hydrotalcite promotes gastric protection and healing via several mechanisms, including increased levels of PGE2 in blood serum, activation of EGF, and antagonising the inhibition of cyclooxygenase (COX) caused by NSAIDs.


Assuntos
Hidróxido de Alumínio/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Indometacina/efeitos adversos , Hidróxido de Magnésio/farmacologia , Úlcera Gástrica/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/sangue , Dinoprostona/metabolismo , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/sangue , Fator de Crescimento Epidérmico/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Proteínas de Membrana/metabolismo , Omeprazol/farmacologia , Ranitidina/farmacologia , Ratos , Ratos Wistar , Estômago/efeitos dos fármacos , Úlcera Gástrica/patologia
16.
Chem Biol Interact ; 308: 45-50, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095933

RESUMO

The flavonoid hesperidin is abundantly found in citrus fruits and is used to treat vascular diseases. Previous studies described its gastroprotective actions against stress or ethanol-induced ulcer in rodents; however, results from indomethacin-induced ulcer were controversy. Therefore, given its clinical use and contradictory findings in acute models, this study aims to evaluate the effect of hesperidin (1-10 mg/kg, p.o) on chronic gastric ulcer induced by acetic acid in rats, a model that resembles the ulcer in humans. Moreover, the effects of hesperidin on mucin levels and on inflammatory and oxidative parameters at ulcer site were also measured. The treatment with hesperidin at 3 and 10 mg/kg, once a day, by seven days, accelerated by 34 and 62%, respectively, the ulcer healing process when compared to vehicle-treated group (99.1 ±â€¯6.4 mm2). Histological and histochemistry analyses confirmed the healing effect with significant favoring of mucin production. Hesperidin also promoted the preservation of reduced glutathione levels in the gastric mucosa tissue, as well as the normalization of superoxide dismutase and catalase activities at similar levels to those found in the non-ulcerated group. In addition, flavonoid administration increased the enzymatic activity of glutathione-S-transferase by 35%. Tissue lipoperoxides and myeloperoxidase activity were reduced after hesperidin treatment. In conclusion, the flavonoid hesperidin revealed a gastric healing activity in the ulcerated mucosa, an effect that showed to be associated with the reduction of oxidative damage at ulcer site, due to the reduction of the neutrophil migration and the strengthening of the mucus barrier next to the mucosa.


Assuntos
Glicosídeos/uso terapêutico , Hesperidina/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Ácido Acético/toxicidade , Animais , Catalase/metabolismo , Esquema de Medicação , Flavanonas/química , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Glicosídeos/farmacologia , Hesperidina/farmacologia , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Cicatrização/efeitos dos fármacos
17.
Medicine (Baltimore) ; 98(20): e15701, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096515

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) is a standard procedure for treating gastric neoplasms. However, ESD causes larger artificial ulcers other than mucosal resection methods. We conducted this prospective randomized controlled study to evaluate the effect of stronger acid suppression on ESD ulcers caused by doubling the proton pump inhibitor (PPI) dose and compare the effects of 20-mg (standard dose) and 40-mg (double dose) esomeprazole (EswonampTM, Daewon Pharmaceutical Co., Ltd., Seoul, Korea) on ulcer healing. METHODS: One hundred ninety-seven patients who underwent gastric ESD from July 2017 to December 2017 at Pusan National University Yangsan Hospital were enrolled and randomly assigned to the standard or double-dose group. Change in ulcer size from the day of ESD to 4 weeks after ESD and the scar-change rate were compared between the groups. RESULTS: There were no significant differences in ulcer contraction (84.5% in 20 mg group vs 86.3% in 40 mg group, P = .91) or scar-change rate (30.9% vs 30.6%, P > .99) between the groups. In a multivariate analysis, initial ulcer size [odds ratio (OR) 0.24; 95% confidence interval (CI) 0.11-0.50] and early gastric cancer (OR 0.22, 95% CI 0.08-0.58) were significantly associated with delayed ulcer healing. CONCLUSIONS: Both 40 and 20-mg esomeprazole have similar effects on ESD-induced ulcer area reduction, suggesting that strong acid suppression does not necessarily result in rapid artificial ulcer healing. TRIAL REGISTRATION NUMBER: RCT no.: KCT0002885.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Esomeprazol/uso terapêutico , Neoplasias Gástricas/cirurgia , Úlcera Gástrica/tratamento farmacológico , Ressecção Endoscópica de Mucosa/métodos , Esomeprazol/administração & dosagem , Feminino , Humanos , Masculino , Estudos Prospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/administração & dosagem , Pirróis/uso terapêutico , República da Coreia/epidemiologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Úlcera Gástrica/patologia , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Úlcera/tratamento farmacológico , Úlcera/patologia , Cicatrização/efeitos dos fármacos
18.
Molecules ; 24(7)2019 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30987044

RESUMO

Stress is an important factor in the etiology of some illnesses such as gastric ulcers and depression. Castilleja tenuiflora Benth. (Orobanchaceae) is used in Mexican traditional medicine for the treatment of gastrointestinal diseases and nervous disorders. Previous studies indicated that organic extracts from C. tenuiflora had gastroprotective effects and antidepressant activity. In this study, we aimed to evaluate the gastroprotective and antidepressant activity of fractions and isolated compounds from the methanolic extract (MECt) of C. tenuiflora in stressed mice. Chromatographic fractionation of MECt produced four fractions (FCt-1, FCt-2, CFt-3, and FCt-4) as well as four bioactive compounds which were identified using TLC, HPLC and NMR analyses. The cold restraint stress (CRS)-induced gastric ulcer model followed by the tail suspension test and the forced swim test were used to evaluate the gastroprotective effect and antidepressant activity of the extract fractions. FCt-2 and FCt-3 at 100 mg/kg had significant gastroprotective and antidepressant effects. All isolated compounds (verbascoside, teniufloroside and mixture geniposide/ musseanoside) displayed gastroprotective effects and antidepressant activity at 1 or 2 mg/kg. The above results allow us to conclude that these polyphenols and iridoids from C. tenuiflora are responsible for the gastroprotective and antidepressant effects.


Assuntos
Iridoides/uso terapêutico , Orobanchaceae/química , Extratos Vegetais/uso terapêutico , Animais , Antiulcerosos/química , Antiulcerosos/uso terapêutico , Antidepressivos/química , Antidepressivos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Glucosídeos/química , Iridoides/química , Masculino , Metanol/química , Camundongos , Fenóis/química , Extratos Vegetais/química , Úlcera Gástrica/tratamento farmacológico
19.
Biofactors ; 45(3): 479-489, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30974027

RESUMO

Baccharis dracunculifolia is a medicinal plant native to southeastern Brazil and is the main botanical source used by bees (Apis mellifera) in the manufacture of green propolis and display similar gastroprotective action and chemical profile. This article reports the healing gastric ulcer activity of the hydroethanolic extract of B. dracunculifolia (HEBD) in an acetic acid-induced ulcer model. In addition to the extract, the isolated compounds ferulic acid, p-coumaric acid, caffeic acid, baccharin, and aromadendrin-4'-O-methyl ether were also assayed. HEBD at a dose of 300 mg/kg reduced the ulcerated area by 49.4% after treatment for 7 days, twice a day. Histological analyses revealed that the margins and base of the ulcer obtained significant regeneration, and periodic acid Schiff base staining showed a 78.2% increase in the mucin levels. The action on the enzymatic antioxidant system demonstrated an increased activity of superoxide dismutase and glutathione-S-transferase, in addition to raising glutathione reduced levels and myeloperoxidase activity. HEBD did not show cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazole bromine test. In vitro, HEBD inhibited the H+ /K+ -ATPase enzyme and showed antioxidant activity in the 2,2 diphenyl-1-picryllydrazyl test. Regarding the isolated compounds, oral administration of p-coumaric acid (15 mg/kg) reduced the ulcerated area by 66.2%. The results suggest that HEBD recovers the gastric ulcerated tissue, raising mucus and antioxidant enzyme levels, and reducing the H+ /K+ -ATPase activity. In addition, the findings confirm that p-coumaric acid is a pivotal bioactive compound on the gastric healing effects elicited by HEBD. © 2019 BioFactors, 45(3):479-489, 2019.


Assuntos
Baccharis/química , Extratos Vegetais/uso terapêutico , Propionatos/metabolismo , Úlcera Gástrica/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismo , Úlcera Gástrica/metabolismo , Superóxido Dismutase/metabolismo
20.
Yakugaku Zasshi ; 139(3): 385-391, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30828015

RESUMO

Sacran, a new polysaccharide isolated from cyanobacterium Aphanothece sacrum (Sur.) Okada, is known to have potential as an active pharmaceutical ingredient (API) for the treatment of atopic dermatitis, various types of dermatitis, skin wound, hemorrhoids and corneal epithelium disorder. In the present studies, the effects of sacran on skin injury and skin pain induced by stratum corneum tape-stripping and gastric ulcer induced by indomethacin, a non-steroidal anti-inflammatory drug (NSAID), and hydrochloride/ethanol (HCl/EtOH) in mice were investigated. Sacran solution 0.05% (w/v) showed greater reduction of skin injury and skin pain induced by stratum corneum tape-stripping, compared to that of 0.01% (w/v) and 0.1% (w/v) sacran solutions. In addition, the inhibitory effects of 0.05% (w/v) sacran on skin injury and skin pain induced by tape-stripping were significantly superior to 0.05% (w/v) hyaluronic acid solution. On the other hand, 1.0% (w/v) sacran solution significantly inhibited gastric ulcer formation induced by indomethacin, compared with 1% (w/v) dextran solution and the inhibitory effect of sacran was comparable to that of the positive control omeprazole. In addition, 1% (w/v) and 2% (w/v) sacran solution reduced HCl/EtOH-induced gastric ulcer in mice, with the alleviative effect of sacran was comparable to or greater than that of the positive control sodium alginate. These results suggest that sacran has potential as API to treat skin injury and pain induced by tape-stripping and gastric ulcer induced by NSAIDs and EtOH.


Assuntos
Cianobactérias/química , Polissacarídeos Bacterianos , Polissacarídeos , Dermatopatias/tratamento farmacológico , Úlcera Gástrica/tratamento farmacológico , Administração Oral , Administração Tópica , Animais , Anti-Inflamatórios não Esteroides , Modelos Animais de Doenças , Humanos , Camundongos , Dor/tratamento farmacológico , Dor/etiologia , Polissacarídeos/administração & dosagem , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos Bacterianos/administração & dosagem , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/uso terapêutico , Pele/lesões , Soluções
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