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1.
Medicine (Baltimore) ; 98(48): e18142, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770250

RESUMO

RATIONALE: Mucormycosis is a rare opportunistic fungal infection with poor prognosis. The incidence of mucormycosis has been increasing, and it is a threat to immunocompromised hosts. We present a case of gastric mucormycosis complicated by a gastropleural fistula during immunosuppressive treatment for adult-onset Still disease (AOSD). PATIENT CONCERNS: An 82-year-old woman diagnosed with AOSD who developed gastric ulcers during the administration of an immunosuppressive therapy with corticosteroids, cyclosporine, and tocilizumab complained of melena and epigastralgia. Esophagogastroduodenoscopy showed multiple ulcers covered with grayish or greenish exudates. DIAGNOSES: The patient diagnosed with mucormycosis based on culture and biopsy of the ulcers, which showed nonseptate hyphae branching at wide angles. Mucor indicus was identified using polymerase chain reaction. INTERVENTIONS AND OUTCOMES: Although liposomal amphotericin B was administered, gastric mucormycosis was found to be complicated by a gastropleural fistula. The patient died because of pneumonia due to cytomegalovirus infection, and autopsy revealed the presence of Mucorales around the fistula connecting the stomach and diaphragm. LESSONS: Gastric mucormycosis is refractory to treatment and fatal. Surgical resection, if possible, along with antifungal drugs can result in better outcomes.


Assuntos
Fístula Gástrica/microbiologia , Mucormicose/complicações , Infecções Oportunistas/complicações , Fístula do Sistema Respiratório/microbiologia , Úlcera Gástrica/microbiologia , Idoso de 80 Anos ou mais , Feminino , Fístula Gástrica/induzido quimicamente , Humanos , Imunossupressores/efeitos adversos , Mucormicose/induzido quimicamente , Mucormicose/microbiologia , Infecções Oportunistas/induzido quimicamente , Infecções Oportunistas/microbiologia , Pleura/microbiologia , Fístula do Sistema Respiratório/induzido quimicamente , Doença de Still de Início Tardio/tratamento farmacológico , Úlcera Gástrica/induzido quimicamente
2.
Eur J Pharm Sci ; 140: 105101, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639436

RESUMO

Gastric irritation and ulcerogenic effect of the acidic NSAIDs are of the most challenging problems in designing novel anti-inflammatory agents. In this study, the new prodrugs were prepared through Steglich esterification reaction between the carboxylic acid functional group of etodolac or tolfenamic acid and thymol. The structures were confirmed by IR, 1H NMR, 13C NMR, mass spectroscopy and elemental analysis. Their chemical stability in addition to a kinetic study of their hydrolysis in 20% liver homogenate and 10% buffered plasma were investigated. In vitro enzymatic hydrolysis showed half-life times 88.84 and 106.61 min for the prodrugs of etodolac and tolfenamic acid, respectively. Their ability to inhibit paw edema and their ulcerogenic potential were assessed in rats and compared to their parent drugs. the prodrugs were found to be stable in different pHs at room and body temperatures. Both prodrugs proved to possess high percentage of inhibition of paw edema (94.68 & 97.1%) in rats comparable to that of the parent drugs (90.33 & 93.23%) and, most importantly with lower ulcerogenic potential. The prodrugs are expected to be converted to their parent drugs rapidly in plasma and liver in vivo and proved to be safer than their parent drugs. The study opens a perspective chance that can be a backbone for further investigations.


Assuntos
Anti-Inflamatórios/síntese química , Edema/tratamento farmacológico , Etodolac/síntese química , Pró-Fármacos/síntese química , Úlcera Gástrica/induzido quimicamente , ortoaminobenzoatos/síntese química , Animais , Anti-Inflamatórios/farmacologia , Desenho de Drogas , Estabilidade de Medicamentos , Etodolac/farmacologia , Feminino , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Cinética , Fígado/metabolismo , Masculino , Estrutura Molecular , Plasma/metabolismo , Pró-Fármacos/farmacologia , Ratos , Ratos Wistar , Úlcera Gástrica/prevenção & controle , Relação Estrutura-Atividade , Temperatura Ambiente , ortoaminobenzoatos/farmacologia
3.
Food Chem Toxicol ; 132: 110739, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31374297

RESUMO

The aim of the study was to investigate the effects of four Aronia melanocarpa-based juices in a rat model of indomethacin-induced gastric ulceration. THE JUICES WERE: AM1 and AM2 (produced from aronia fruits at 20 °C and 60 °C, respectively), AMRC (a mixture of AM2 with Rosa canina extract) and AMAV (aronia juice with Alchemilla vulgaris). Male Wistar rats were used. Each of the juices (10 ml/kg) was administered for 10 days. Indomethacin (30 mg/kg) was injected subcutaneously and after 4 h, the effects were estimated. Indomethacin caused heavy destructions of the gastric mucosa, increased the expression of Bax and decreased the expression of Bcl-2, induced a certain increase in lipid peroxidation and a slight decrease in gastric PGE2 content. The pretreatment with the juices reduced the severity of indomethacin-induced gastric lesions and antagonized the effects of indomethacin on apoptosis and lipid peroxidation. The highest was the protective effect of AMAV, the juice with the highest polyphenolic content. The protective effect of Aronia melanocarpa-based juices against indomethacin-induced gastric lesions could be attributed to their polyphenolic contents. The mechanism involved to the highest extent in the protective effect of the juices was the inhibition of apoptosis.


Assuntos
Alchemilla/química , Anti-Inflamatórios não Esteroides/toxicidade , Sucos de Frutas e Vegetais , Indometacina/toxicidade , Extratos Vegetais/farmacologia , Rosa/química , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Dinoprostona/metabolismo , Modelos Animais de Doenças , Masculino , Fenóis/análise , Photinia , Compostos Fitoquímicos/análise , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
4.
Pediatrics ; 144(3)2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31375532

RESUMO

A 16-year-old girl presented to the emergency department with intermittent fevers and worsening abdominal pain of 5 weeks duration. She had a history of travel to a less developed country and exposure to possible infectious diseases. Abdominal imaging and blood tests revealed diffuse mesenteric lymphadenopathy, elevated transaminases, and elevation of inflammatory markers. Gastroesophageal and colon endoscopies revealed gastric ulcers, and the patient was discharged with a presumptive diagnosis of systemic juvenile idiopathic arthritis given the lymphadenopathy seen on imaging, serositis, sacroiliac joint stiffness noted on physical examination, and pain relief with celecoxib. She presented again 4 days later with worsening abdominal tenderness, elevated transaminases, and new-onset abdominal distention. Tissue biopsy yielded the diagnosis and directed appropriate treatment.


Assuntos
Dor Abdominal/etiologia , Febre/etiologia , Linfoma Anaplásico de Células Grandes/diagnóstico , Adolescente , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Artrite Juvenil/diagnóstico , Biomarcadores/sangue , Biópsia , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Endoscopia Gastrointestinal , Enterobíase/diagnóstico , Feminino , Humanos , Inflamação/diagnóstico , Linfadenopatia/diagnóstico , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/diagnóstico , Tomografia Computadorizada por Raios X , Transaminases/sangue
5.
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
6.
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
7.
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
8.
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
9.
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
10.
Free Radic Res ; 53(6): 596-610, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31215272

RESUMO

The cytoprotective action of the synthetic resveratrol (Resv) congener, E-3,3',5,5'-tetrahydroxystilbene (designated as HST-1) against indomethacin (IND)-induced stomach ulceration has been established using a mice model. HST-1 reversed the adverse effects of IND on several inflammatory (myeloperoxidase, cytokines, adhesion molecules etc.) and ulcer-healing (cyclooxygenases, prostaglandin, growth factors and their receptors etc.) parameters in mice. More importantly, HST-1 down-regulated TNF-α and the TNF-α-mediated activation of NF-κB and JNK/MAPK pathways that are the key determinants in the IND-gastropathy. The effect of HST-1 on all these factors was significantly better than that of Resv, misoprostol, and omeprazole. HST-1 also did not induce small intestinal mucosal injury, unlike some of the proton pump inhibitors. On the other hand, Resv reduced activation of the prosurvival ERK1/2 pathway that may explain its contraindicative property in the gastrointestinal tract.


Assuntos
Antiulcerosos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Resveratrol/farmacologia , Úlcera Gástrica/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Indometacina , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos , NF-kappa B/metabolismo , Resveratrol/administração & dosagem , Úlcera Gástrica/induzido quimicamente , Fator de Necrose Tumoral alfa/metabolismo
11.
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
12.
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
13.
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
14.
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
15.
Biomed Res Int ; 2019: 9514703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949513

RESUMO

Gastric ulcers are a common problem in upper gastrointestinal tract (GI) disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most aggressive factors leading to inducing gastric ulcers. Natural products with lower toxicity and safety are currently sought as a potential source to minimize the effect of the gastric ulcers. Perilla frutescens or Nga-mon (in Thai) leaves are rich in rosmarinic acid (RA), which has antioxidant, anti-inflammatory, and anticancer effects. This study investigates the protective effect of ethanolic extract (EE) and aqueous fraction (AF) from Perilla frutescens leaves, which are rich in RA, on indomethacin- (IND-) induced gastric ulcer in a rat model. The EE at the doses of 50 and 500 mg/kg body weight, AF at the doses of 50, 250, and 500 mg/kg body weight, or famotidine (a standard drug) were administered for 14 days prior to ulcer induction. The ulceration was performed by intragastric administration of IND. Gross gastric ulcers and biological and histological parameters were examined. The pretreatment with AF had more significant effects than EE, including reduced ulcer index, decreased gastric secretion volume and decreased acidity, but it had an elevated gastric pH relative to the IND-induced gastric ulcer. In a histopathological study, the EE and AF decreased mucosal ulcer, inflammatory infiltration, and degenerative lining cells. The IND-induced expression of inflammatory mediators was significantly attenuated with EE and AF. The experiment also remarkably showed the preservation of mucus and apoptosis protection of EE and AF on a gastric mucosal ulcer. The findings demonstrated that the EE and AF of perilla leaves were capable of protecting the stomach against gastric ulcers induced by IND through anti-inflammatory and antiapoptotic mechanisms that should be further investigated. It is suggested that Perilla frutescens leaf could be a potential alternative source of RA as a therapeutic agent and food supplement for NSAID-induced gastric injuries.


Assuntos
Cinamatos , Depsídeos , Indometacina/efeitos adversos , Perilla frutescens/química , Folhas de Planta/química , Úlcera Gástrica , Animais , Cinamatos/química , Cinamatos/farmacologia , Depsídeos/química , Depsídeos/farmacologia , Relação Dose-Resposta a Droga , Indometacina/farmacologia , Masculino , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Úlcera Gástrica/prevenção & controle
16.
Biomed Res Int ; 2019: 8759708, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30906783

RESUMO

Rubus crataegifolius (black raspberry, RF), Ulmus macrocarpa (elm, UL), and Gardenia jasminoides (cape jasmine, GJ) are well known for hundreds of years as folk medicines in China and Korea to treat various gastrointestinal disturbance. The present study evaluated the gastroprotective effects of these plants either single or in combination against HCl/EtOH-induced gastritis and indomethacin-induced ulcer in rat model. Stomach ulcer was induced by oral ingestions of HCl/EtOH or indomethacin. Treatment with RF, UL, and GJ separately or in combination was done 1 h before ulcer induction. On HCl/EtOH-induced gastritis RF, UL, and GJ at a dose of 150 mg/kg showed comparable antigastritis effect (less than 50% inhibition) with lesion index of 94.97±8.05, 108.48±11.51, and 79.10±9.77 mm compared to cimetidine (45.33±23.73 mm). However, the combination of RF, UL, and GJ at a dose of 150 mg/kg with a ratio of 50:50:50 showed remarkable antigastritis effect with 77% inhibition. The observed lesion index at a ratio of 50:50:50 was 23.34±9.11 mm similar to cimetidine (18.88±19.88 mm). On indomethacin-induced ulcer, RF and GJ showed 38.28% and 51.8% inhibition whereas UL showed around 17.73% inhibition at 150 mg/kg. Combination of RF, UL, and GJ at 150 mg/kg showed strong antigastritis effect with 83.71% inhibition. These findings suggest strong gastroprotective effect of combined extract. In addition, these plants showed significant antioxidant activity in DPPH scavenging assay and antilipid peroxidation activity. Combination of black raspberry, elm, and cape jasmine might be a significant systemic gastroprotective agent that could be utilized for the treatment and/or protection of gastritis and gastric ulcer.


Assuntos
Mucosa Gástrica/lesões , Gastrite/tratamento farmacológico , Extratos Vegetais/farmacologia , Folhas de Planta/química , Úlcera Gástrica/tratamento farmacológico , Animais , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/metabolismo , Gastrite/patologia , Indometacina/efeitos adversos , Indometacina/farmacologia , Masculino , Fitoterapia/métodos , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia
17.
Life Sci ; 224: 88-94, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30914317

RESUMO

AIMS: Several natural products have been evaluated for management of gastric ulcer induced by non-steroidal anti-inflammatory drugs. Safranal, a plant-derived chemical, has a potent antioxidant and anti-inflammatory properties. The present study was aimed to evaluate possible gastro-protective effects of safranal against indomethacin-induced gastric ulcer in rats. Lansoprazole (a proton pump inhibitor) was used as a reference drug. MATERIALS AND METHODS: Thirty rats were divided into five groups. Groups 1 and 2 received vehicle. Groups 3, 4 and 5 treated with 0.063, 0.25 and 1 mg/kg safranal. Group 6 received 30 mg/kg lansoprazole. All groups except of group 1 received indomethacin (50 mg/kg) ingestion. Six hours later, animals were euthanized and their stomachs were removed. Gastric contents volume and pH were measured. Gastric ulcer area and protective index were evaluated using image J software. Histological changes were evaluated by light microscope. Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) content, tumor necrosis factor-alpha (TNF-α) and Caspase-3 levels were determined in the gastric tissue. KEY FINDINGS: Safranal and lansoprazole normalized gastric volume and pH, reduced gastric ulcer area and produced gastric protection. Indomethacin-induced histological changes and tissue biochemical alterations were ameliorated by the above-mentioned treatments. SIGNIFICANCE: The results of the present study suggest the involvement of anti-secretory, anti-oxidant, anti-inflammatory and anti-apoptotic mechanisms in gastro-protective effect of safranal. In addition, gastro-protective effect of safranal was comparable to lansoprazole.


Assuntos
Antiulcerosos/farmacologia , Cicloexenos/farmacologia , Indometacina/toxicidade , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Úlcera Gástrica/prevenção & controle , Terpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Crocus/química , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
18.
Medicina (Kaunas) ; 55(3)2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30862060

RESUMO

Background and objectives: Zingerone is an ingredient of ginger (Zingiber officinale) with different pharmacological activities. Several studies have investigated the effect of zingerone on various gastrointestinal diseases, including irritable bowel syndrome and diarrhea. This study is aimed to evaluate the effect of zingerone on ethanol-induced gastric ulcers in rats. Materials and Methods: Gastric ulcers were induced by ethanol (96%, 5 mL/kg, po) in male wistar rats and zingerone (50, 100, and 200 mg/kg) was administrated orally. Normal saline and ranitidine were used as negative and positive control, respectively. In this study, the number and length of ulcers, and malondialdehyde (MDA) and nitric oxide (NO) levels in stomach tissues were determined. Results: The findings showed that the mean number and length of gastric ulcers were significantly lower in zingerone-received groups than ethanol group (P < 0.05). The level of malondialdehyde was decreased in the stomach of zingerone groups (P < 0.05) compared to the ethanol group. In addition, zingerone treatment prevented the decrease of nitric oxide level by ethanol in the stomach tissue. Conclusions: The present study showed that zingerone has a protective effect on the ethanol-induced gastric ulcer, which may be due to its free radical scavenging activity.


Assuntos
Antiulcerosos/uso terapêutico , Gengibre/química , Guaiacol/análogos & derivados , Fitoterapia , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/patologia , Animais , Antiulcerosos/administração & dosagem , Antiulcerosos/farmacologia , Modelos Animais de Doenças , Etanol/administração & dosagem , Etanol/efeitos adversos , Etanol/farmacologia , Mucosa Gástrica/metabolismo , Guaiacol/administração & dosagem , Guaiacol/farmacologia , Guaiacol/uso terapêutico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Necrose , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Solventes/administração & dosagem , Solventes/efeitos adversos , Solventes/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle
19.
J Basic Clin Physiol Pharmacol ; 30(2): 195-203, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30730837

RESUMO

Background Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70. Methods ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment. Results Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice. Conclusions Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.


Assuntos
Anti-Inflamatórios não Esteroides/toxicidade , Fluvoxamina/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Úlcera Gástrica/prevenção & controle , Animais , Antiulcerosos/farmacologia , Modelos Animais de Doenças , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/prevenção & controle , Proteínas de Choque Térmico HSP70/genética , Indometacina/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Restrição Física , Inibidores de Captação de Serotonina/farmacologia , Úlcera Gástrica/induzido quimicamente , Estresse Psicológico/complicações
20.
Molecules ; 24(3)2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30754621

RESUMO

Peptic ulcers are currently treated with various drugs, all having serious side effects. The aim of this study was to evaluate the gastroprotective activity of calein D (from Calea urticifolia), a sesquiterpene lactone with a germacrane skeleton. Gastric lesions were induced in mice by administering ethanol (0.2 mL) after oral treatment with calein D at 3, 10 and 30 mg/kg, resulting in 13.15 ± 3.44%, 77.65 ± 7.38% and 95.76 ± 2.18% gastroprotection, respectively, to be compared with that of the control group. The effect found for 30 mg/kg of calein D was not reversed by pretreatment with NG-nitro-l-arginine methyl ester (l-NAME, 70 mg/kg, ip), indomethacin (10 mg/kg, sc) or N-ethylmaleimide (NEM, 10 mg/kg, sc). Hence, the mechanism of action of calein D does not involve NO, prostaglandins or sulfhydryl compounds. Calein D was more potent than carbenoxolone, the reference drug. The findings for the latter are in agreement with previous reports.


Assuntos
Asteraceae/química , Etanol/efeitos adversos , Lactonas/administração & dosagem , Sesquiterpenos de Germacrano/administração & dosagem , Úlcera Gástrica/prevenção & controle , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etilmaleimida/administração & dosagem , Etilmaleimida/farmacologia , Indometacina/administração & dosagem , Indometacina/farmacologia , Lactonas/química , Lactonas/farmacologia , Camundongos , Estrutura Molecular , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Prostaglandinas/metabolismo , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Compostos de Sulfidrila/metabolismo
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