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1.
Life Sci ; 239: 117064, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31734260

RESUMO

AIMS: Currently, chronic gastritis is a high incidence of digestive diseases, along with loss of appetite, abdominal pain and diarrhea. Baicalin belongs to the major bioactive flavonoids compounds from Scutellariae Radix, it exhibited anti-inflammatory and anti-bacteria activities. Nonetheless, the protective effects of baicalin on ethanol-induced gastritis have not been completely clarified. Our study was designed to evaluate the protective activity of baicalin on ethanol-induced chronic gastritis. MAIN METHODS: Rat with chronic gastritis model was induced by the administration of 56% ethanol for four weeks. Baicalin (50 and 100 mg/kg) were orally administered for seven days to evaluate its curative effect, respectively. The production of TNF-α, interleukin (IL)-8, IL-1ß, NO, ET-1, PGE2, LDH and COX-2 were determined by ELISA. The activities of Akt, p-Akt, IκBα, p-IκBα, NF-κBp65 and NF-κBp-p65 were tested by western blot. Immunofluorescence staining was employed to assess the location of NF-κBp65. KEY FINDINGS: The changes of the histopathological analysis and the levels of NO, ET-1, PGE2, LDH and COX-2 demonstrated that baicalin treatment ameliorated ethanol-induced gastritis. ELISA analysis showed that baicalin inhibited the levels of TNF-α, IL-8 and IL-1ß. Besides, Akt, p-Akt, IκBα, p-IκBα, NF-κBp65 and NF-κBp-p65 expression were significantly suppressed by baicalin. Meanwhile, baicalin suppressed the translocation of NF-κBp65 to the cell nucleus through immunofluorescence staining, molecular docking analysis showed that baicalin had affinity with Akt and NF-κBp65. SIGNIFICANCE: All results demonstrated that baicalin effectively alleviated chronic gastritis via suppressing the levels of inflammatory regulators and inhibiting Akt/NF-κB activation.


Assuntos
Flavonoides/farmacologia , Gastrite/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Etanol/efeitos adversos , Etanol/farmacologia , Flavonoides/metabolismo , Gastrite/prevenção & controle , Masculino , NF-kappa B/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensis , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
2.
Int J Biol Macromol ; 141: 68-75, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31446106

RESUMO

Galactomannans are neutral polysaccharides isolated from the endosperm of some Leguminosae seeds. They consist of a (1 → 4) linked ß-mannopyranosyl backbone partially substituted at O-6 with α-d-galactopyranosyl side groups. C. pulcherrima have anti-inflammatory and muco-adhesive proprieties. Acute gastritis is an inflammatory disease triggered by use of non-steroidal anti-inflammatory drugs. We investigated the gastroprotective effect of galactomannan obtained from the seeds of Caesalpinia pulcherrima L. (GM-CP) in acute gastritis model induced by indomethacin. Gastritis was induced with indomethacin (30 mg/kg, P.·O.) in female Swiss mice. Animal groups (n = 7) were pretreated with saline-dissolved GM-CP (3 mg/kg, 10 mg/kg, 30 mg/kg, P.O.) or vehicle 1 h before gastritis induction. Mice were euthanized seven hours after the induction. The stomach and blood samples were collected for analysis. At 10 mg/kg, GP-CP reduced the extension of macroscopic lesion and the loss of superficial cells by alleviating inflammatory symptoms (neutrophil infiltration, migration and adhesion of mesenteric leukocytes, production of TNF-α and thiobarbituric acid reactive species (TBARS) and helping to maintain mucin labeling of the tissue. Thus, the findings of the study suggest that GM-CP exhibits gastroprotective effects.


Assuntos
Caesalpinia/química , Gastrite , Indometacina/efeitos adversos , Mananas/farmacologia , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Sementes/química , Doença Aguda , Animais , Feminino , Gastrite/induzido quimicamente , Gastrite/metabolismo , Gastrite/patologia , Gastrite/prevenção & controle , Indometacina/farmacologia , Mananas/química , Camundongos , Neutrófilos/patologia
3.
Biomolecules ; 9(4)2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30987336

RESUMO

Anji white tea (Camellia sinensis) is a traditional Chinese tea beverage, which is classified as green tea and contains an abundant amount of flavonoids. In this study, the preventive effect of Anji white tea flavonoids (AJWTFs) on ethanol/hydrochloric acid-induced gastric injury in mice was evaluated. The serum and gastric tissues of mice were analyzed using a biochemical kit and by quantitative polymerase chain reaction (qPCR). Observation of the appearance of the stomach indicated that AJWTFs could effectively reduce the area of gastric injury caused by ethanol/hydrochloric acid, and the inhibition rate of AJWTF on gastric injury increased with an increase in AJWTF concentration. The Anji white tea flavonoids could also reduce the volume and pH of gastric juice in mice with gastric injury. Biochemical results showed that AJWTFs could increase the superoxide dismutase (SOD) and glutathione (GSH) activities, as well as decrease the malondialdehyde (MDA) level, in the serum and liver of mice with gastric injury. Pathological observation confirmed that AJWTFs could inhibit the tissue damage caused by ethanol/hydrochloric acid in the stomach of mice. Further qPCR experiments also showed that AJWTFs could inhibit the decreases in neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), copper/zinc superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), and the increase in inducible nitric oxide synthase (iNOS) expression in the gastric tissue of mice caused by gastric injury. As observed, AJWTFs exerted a good preventive effect on alcohol-induced gastric injury in mice induced by ethanol/hydrochloric acid, and the effect is close to that of ranitidine. Anji white tea flavonoids present good antioxidant effect, which allows them to effectively prevent alcoholic gastric injury and be used as biologically active substances with a broad range of applications.


Assuntos
Transtornos Induzidos por Álcool/prevenção & controle , Antioxidantes/uso terapêutico , Camellia sinensis/química , Flavonoides/uso terapêutico , Gastrite/prevenção & controle , Extratos Vegetais/uso terapêutico , Animais , Antioxidantes/farmacologia , Catalase/metabolismo , Flavonoides/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Óxido Nítrico Sintase/metabolismo , Extratos Vegetais/farmacologia , Superóxido Dismutase/metabolismo
4.
Adv Exp Med Biol ; 1149: 257-275, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016627

RESUMO

Helicobacter pylori is a highly-adapted gastrointestinal pathogen of humans and the immunology of this chronic infection is extremely complex. Despite the availability of antibiotic therapy, the global incidence of H. pylori infection remains high, particularly in low to middle-income nations. Failure of therapy and the spread of antibiotic resistance among the bacteria are significant problems and provide impetus for the development of new therapies and vaccines to treat or prevent gastric ulcer, and gastric carcinoma. The expansion of knowledge on gastric conventional and regulatory T cell responses, and the role of TH17 in chronic gastritis from studies in mouse models and patients have provided valuable insights into how gastritis is initiated and maintained. The development of human challenge models for testing candidate vaccines has meant a unique opportunity to study acute infection, but the field of vaccine development has not progressed as rapidly as anticipated. One clear lesson learned from previous studies is that we need a better understanding of the immune suppressive mechanisms in vivo to be able to design vaccine strategies. There is still an urgent need to identify practical surrogate markers of protection that could be deployed in future field vaccine trials. Important developments in our understanding of the chronic inflammatory response, progress and problems arising from human studies, and an outlook for the future of clinical vaccine trials will be discussed.


Assuntos
Vacinas Bacterianas , Gastrite , Infecções por Helicobacter , Helicobacter pylori , Animais , Vacinas Bacterianas/imunologia , Gastrite/microbiologia , Gastrite/prevenção & controle , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/imunologia , Humanos
5.
Pharm Res ; 36(4): 52, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30783816

RESUMO

PURPOSE: Tetramethylpyrazine-loaded poloxamer hydrogel materials were studied to achieve the controlled release of tetramethylpyrazine. METHODS: First, hydrogels having different concentrations of poloxamer 407 and poloxamer 188 were prepared. The gelling temperature and viscosity were measured. Second, we investigated the tetramethylpyrazine release rate from the thermosensitive poloxamer hydrogel materials in vitro and ex vivo. Finally, further study of the pharmacological efficacy of the tetramethylpyrazine-loaded thermosensitive poloxamer hydrogel materials was also investigated in vivo. RESULTS: The in vitro, ex vivo and in vivo experimental results showed that the tetramethylpyrazine-loaded poloxamer hydrogel with the appropriate gelling temperature, good adhesion and easy preparation controlled the release of tetramethylpyrazine. CONCLUSIONS: The hydrogel with the suitable nasal temperature and a satisfactory adhesion was selected. The relevant tests were carried out, including the determination of the concentration of drugs in the brain homogenate and the anti-inflammatory test after different modes of administration. So the poloxamer hydrogel was a novel carrier to deliver TMP to pass across the blood brain barrier via nasal administration.


Assuntos
Anti-Inflamatórios/administração & dosagem , Portadores de Fármacos , Gastrite/prevenção & controle , Poloxâmero/química , Pirazinas/administração & dosagem , Temperatura , Ácido Acético , Adesividade , Administração Cutânea , Administração Intranasal , Administração Oral , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Permeabilidade Capilar , Química Farmacêutica/métodos , Preparações de Ação Retardada , Modelos Animais de Doenças , Composição de Medicamentos , Liberação Controlada de Fármacos , Gastrite/induzido quimicamente , Hidrogéis , Pirazinas/química , Pirazinas/farmacocinética , Ratos Sprague-Dawley , Viscosidade
6.
Helicobacter ; 24(2): e12563, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30672082

RESUMO

BACKGROUND: The high prevalence of Helicobacter pylori (H pylori) infection in China results in a substantial public health burden. Medical experts have not agreed on the best solution of population intervention for this problem. We presented a health economic evaluation of a population-based H pylori screen-and-treat strategy for preventing gastric cancer, peptic ulcer disease (PUD), and nonulcer dyspepsia (NUD). MATERIALS AND METHODS: Decision trees and Markov models were developed to evaluate the cost-effectiveness of H pylori screening followed by eradication treatment in asymptomatic Chinese. The modeled screen-and-treat strategy reduced the risk of gastric cancer, PUD, and NUD. The main outcomes were the costs, effectiveness, and the incremental cost-effectiveness ratio. Uncertainty was explored by one-way and probabilistic sensitivity analyses. RESULTS: For preventing gastric cancer, PUD, and NUD together in a cohort of 10 million asymptomatic Chinese at the age of 20 years, the H pylori screen-and-treat strategy saved 288.1 million dollars, 28 989 life years, and 111 663 quality-adjusted life years, and prevented 11 611 gastric cancers, 5422 deaths from gastric cancer, and 1854 deaths from PUD during life expectancy. Uncertainty of screening age from 20 to 60 did not affect the superiority of the screen-and-treat strategy over the no-screen strategy. The one-way and probabilistic sensitivity analyses confirmed the robustness of our study's results. CONCLUSIONS: Compared with the no-screen strategy, population-based screen-and-treat strategy for H pylori infection proved cheaper and more effective for preventing gastric cancer, PUD, and NUD in Chinese asymptomatic general population.


Assuntos
Doenças Assintomáticas/terapia , Análise Custo-Benefício , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Programas de Rastreamento/economia , Doenças Assintomáticas/economia , China , Dispepsia/complicações , Dispepsia/prevenção & controle , Gastrite/complicações , Gastrite/diagnóstico , Gastrite/prevenção & controle , Infecções por Helicobacter/complicações , Infecções por Helicobacter/economia , Infecções por Helicobacter/prevenção & controle , Humanos , Cadeias de Markov , Úlcera Péptica/complicações , Úlcera Péptica/prevenção & controle , Neoplasias Gástricas/complicações , Neoplasias Gástricas/prevenção & controle
7.
Nutrients ; 11(1)2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30669695

RESUMO

This study aimed to evaluate the effect of Lactobacillus reuteri DSM 17938 (DSM) on ethanol-induced gastric injury, and if its possible mechanism of action is related to inhibiting the transient receptor potential vanilloid type 1 (TRPV1). We evaluated the effect of supplementing 108 CFU•g body wt-1•day-1 of DSM on ethanol-induced gastric injury. DSM significantly reduced the ulcer area (1.940 ± 1.121 mm²) with 3 days of pretreatment. The effects of DSM supplementation were reversed by Resiniferatoxin (RTX), TRPV1 agonist (3 nmol/kg p.o.). Substance P (SP) (1 µmol/L per 20 g) plus 50% ethanol resulted in hemorrhagic lesions, and DSM supplementation did not reverse the lesion area induced by administering SP. TRPV1 staining intensity was lower, SP, malondialdehyde (MDA) and nitrite levels were reduced, and restored normal levels of antioxidant parameters (glutathione and superoxide dismutase) in the gastric mucosa in mice treated with DSM. In conclusion, DSM exhibited gastroprotective activity through decreased expression of TRPV1 receptor and decreasing SP levels, with a consequent reduction of oxidative stress.


Assuntos
Etanol/efeitos adversos , Mucosa Gástrica/patologia , Lactobacillus reuteri/crescimento & desenvolvimento , Probióticos/uso terapêutico , Úlcera Gástrica/prevenção & controle , Substância P/antagonistas & inibidores , Canais de Cátion TRPV/antagonistas & inibidores , Animais , Antioxidantes/metabolismo , Diterpenos/farmacologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/induzido quimicamente , Gastrite/metabolismo , Gastrite/prevenção & controle , Glutationa/metabolismo , Lactobacillus reuteri/classificação , Malondialdeído/metabolismo , Camundongos , Substâncias Protetoras/uso terapêutico , Especificidade da Espécie , Estômago/microbiologia , Estômago/patologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Superóxido Dismutase/metabolismo , Canais de Cátion TRPV/farmacologia
8.
J Clin Invest ; 129(3): 1345-1358, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30652972

RESUMO

In the stomach, chronic inflammation causes metaplasia and creates a favorable environment for the evolution of gastric cancer. Glucocorticoids are steroid hormones that repress proinflammatory stimuli, but their role in the stomach is unknown. In this study, we show that endogenous glucocorticoids are required to maintain gastric homeostasis. Removal of circulating glucocorticoids in mice by adrenalectomy resulted in the rapid onset of spontaneous gastric inflammation, oxyntic atrophy, and spasmolytic polypeptide-expressing metaplasia (SPEM), a putative precursor of gastric cancer. SPEM and oxyntic atrophy occurred independently of lymphocytes. However, depletion of monocytes and macrophages by clodronate treatment or inhibition of gastric monocyte infiltration using the Cx3cr1 knockout mouse model prevented SPEM development. Our results highlight the requirement for endogenous glucocorticoid signaling within the stomach to prevent spontaneous gastric inflammation and metaplasia, and suggest that glucocorticoid deficiency may lead to gastric cancer development.


Assuntos
Gastrite , Glucocorticoides/metabolismo , Lesões Pré-Cancerosas , Neoplasias Gástricas , Estômago/patologia , Animais , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Gastrite/genética , Gastrite/metabolismo , Gastrite/prevenção & controle , Glucocorticoides/genética , Humanos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Inflamação/prevenção & controle , Metaplasia , Camundongos , Camundongos Knockout , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/prevenção & controle , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle
9.
Korean J Intern Med ; 34(5): 1008-1021, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29847892

RESUMO

BACKGROUND/AIMS: Irsogladine maleate, an enhancer of gastric mucosal protective factors, has demonstrated its efficacy for various gastric mucosal injuries. The aim of this study was to evaluate the efficacy and safety of irsogladine for prevention of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin-induced peptic ulcer and gastritis. METHODS: In this multicenter, randomized, double-blind, exploratory clinical trial, 100 patients over 50 years of age who needed continuous NSAIDs or aspirin for more than 8 weeks were randomly assigned to either test group (irsogladine maleate 2 mg, twice daily, 39 patients for full analysis) or placebo group (37 patients for full analysis). Primary outcomes were incidence of peptic ulcer and ratio of modified Lanza score (MLS) 2 to 4. Secondary outcome was the number of acute erosions confirmed by endoscopy at 8 weeks. Adverse effects were also compared. RESULTS: There were no significant differences in gastric protective effects between test and placebo groups. However, two cases of peptic ulcer in the placebo group but none in the test group were observed. These two cases of peptic ulcer were Helicobacter pylori-negative. In addition, H. pylori-negative group showed significant changes in MLS score (p = 0.0247) and edema score (p = 0.0154) after the treatment compared to those before treatment in the test group. There was no significant difference in adverse events between the two groups. CONCLUSION: The efficacy of irsogladine maleate was found in H. pylori-negative group, suggesting its potential as a protective agent against NSAIDs or aspirin-induced peptic ulcer and gastritis.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Gastrite/prevenção & controle , Úlcera Gástrica/prevenção & controle , Triazinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/efeitos adversos , Método Duplo-Cego , Feminino , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Fatores de Risco , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Triazinas/efeitos adversos
10.
Biosci Biotechnol Biochem ; 83(1): 166-173, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30286691

RESUMO

Inflammation induced by Helicobacter pylori infection related to gastric carcinogenesis. In this study, we have investigated the anti-inflammatory effect and its mechanism of kaempferol in the inflammatory response caused by H. pylori infection in vitro. We found that kaempferol reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-8) and production of IL-8 in AGS cells. In addition, kaempferol suppressed translocation of cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) of H. pylori to AGS cells. It was due to decreased transcription of type IV secretion system (T4SS) components involved in CagA injection and secretion system subunit protein A (SecA) of type V secretion system (T5SS) involved in VacA secretion by kaempferol. In conclusion, kaempferol shows the anti-inflammatory effect by suppressing the translocation of CagA and VacA proteins and leading to the down-regulation of pro-inflammatory cytokines. Abbreviations: CagA: cytotoxin-associated gene A; VacA: vacuolating cytotoxin A; T4SS: type IV secretion systems; SecA: secretion system subunit protein A; T5SS: type V secretion system.


Assuntos
Anti-Inflamatórios/farmacologia , Gastrite/microbiologia , Gastrite/prevenção & controle , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Inflamação/prevenção & controle , Quempferóis/farmacologia , Antígenos de Bactérias/efeitos dos fármacos , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/crescimento & desenvolvimento , Humanos , Inflamação/etiologia , Mediadores da Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/biossíntese , Interleucina-8/metabolismo , Transporte Proteico/efeitos dos fármacos , Fator de Crescimento Transformador alfa/metabolismo
11.
Int Immunopharmacol ; 64: 116-122, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30173051

RESUMO

Melatonin has important immuno-regulatory effects in inflammatory disorders but its specific role in Helicobacter pylori induced gastritis remains unclear. The aim of our study was to analyze the activity of melatonin against H. pylori induced gastritis in vivo, and explore the underlying mechanisms. The H. pylori infected mice showed extensive inflammatory cell infiltration in the gastric mucosa and submucosa, along with significantly reduced spleen and thymus weight. However, 2 and 6 weeks of treatment with 25 and 50 mg/kg melatonin restored the thymus weights relative to that of the untreated mice. TLR2 was upregulated in the gastric mucosa of the infected mice, which was restored to normal levels after 2 and 6 weeks of melatonin treatment. In contrast, TLR4 levels were similar between the treated and untreated mice. Furthermore, melatonin treatment restored spleen Foxp3 and serum TGF-ß1 levels that were respectively increased and decreased in the infected mice. H. pylori infected mice also showed a decrease in the serum levels of IL-2, IL-6, IL-10, IL-17, IFN-γ and TFN-α following 2 and 6 weeks of melatonin treatment compared to the untreated mice. Melatonin treatment also resulted in decreased CD4+CD25+Foxp3+ Treg cell count in the spleen. The expression of TLR2, MyD88, p-ERK, p-p38, p65, p50 and Foxp3 in the gastric tissues were lower in the untreated mice compared to mice treated with melatonin for 2 weeks. However, the expression levels evened out after 6 weeks of treatment. Taken together, melatonin alleviates H. pylori induced gastritis by regulating TGF-ß1 and Foxp3 expression via the TLR2 and TLR4 pathways.


Assuntos
Citocinas/biossíntese , Fatores de Transcrição Forkhead/genética , Gastrite/prevenção & controle , Infecções por Helicobacter/complicações , Helicobacter pylori , Melatonina/farmacologia , Receptor 2 Toll-Like/fisiologia , Receptor 4 Toll-Like/fisiologia , Animais , Regulação para Baixo , Melatonina/uso terapêutico , Camundongos , NF-kappa B/fisiologia , Receptor 2 Toll-Like/análise , Receptor 4 Toll-Like/análise , Fator de Crescimento Transformador beta1/sangue
12.
Nutrients ; 10(9)2018 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-30231525

RESUMO

Helicobacter pylori (H. pylori) infection leads to gastric inflammation, peptic ulcer and gastric carcinoma. H. pylori activates NADPH oxidase and increases reactive oxygen species (ROS), which induce NF-κB activation and IL-8 expression in gastric epithelial cells. Dysfunctional mitochondria trigger inflammatory cytokine production. Peroxisome proliferator-activated receptors-γ (PPAR-γ) regulate inflammatory response. Astaxanthin is a powerful antioxidant that protects cells against oxidative stress. The present study was aimed at determining whether astaxanthin inhibits H. pylori-induced mitochondrial dysfunction, NF-κB activation, and IL-8 expression via PPAR-γ activation in gastric epithelial cells. Gastric epithelial AGS cells were treated with astaxanthin, NADPH oxidase inhibitor apocynin and PPAR-γ antagonist GW9662, and infected with H. pylori. As a result, H. pylori caused an increase in intracellular and mitochondrial ROS, NF-κB activation and IL-8 expression, but decreased mitochondrial membrane potential and ATP level. Astaxanthin inhibited H. pylori-induced alterations (increased ROS, mitochondrial dysfunction, NF-κB activation, and IL-8 expression). Astaxanthin activated PPAR-γ and its target gene catalase in H. pylori-infected cells. Apocynin reduced ROS and inhibited IL-8 expression while astaxanthin did not affect NADPH oxidase activity. Inhibitory effects of astaxanthin on ROS levels and IL-8 expression were suppressed by addition of GW9662. In conclusion, astaxanthin inhibits H. pylori-induced mitochondrial dysfunction and ROS-mediated IL-8 expression by activating PPAR-γ and catalase in gastric epithelial cells. Astaxanthin may be beneficial for preventing oxidative stress-mediated gastric inflammation-associated H. pylori infection.


Assuntos
Antioxidantes/farmacologia , Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Gastrite/prevenção & controle , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Interleucina-8/metabolismo , Mitocôndrias/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/metabolismo , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Interações Hospedeiro-Patógeno , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/microbiologia , Mitocôndrias/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xantofilas/farmacologia
13.
Lancet Gastroenterol Hepatol ; 3(10): 698-707, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30042064

RESUMO

BACKGROUND: Intramuscular immunisation with a vaccine composed of three recombinant Helicobacter pylori antigens-vacuolating cytotoxin A (VacA), cytotoxin-associated antigen (CagA), and neutrophil-activating protein (NAP)-prevented infection in animal models and was well tolerated and highly immunogenic in healthy adults. We aimed to assess the efficacy of the vaccine in prevention of a H pylori infection after challenge with a CagA-positive strain (BCM 300) in healthy volunteers. METHODS: In this randomised phase 1/2, observer-blind, placebo-controlled, single-centre study, healthy non-pregnant adults aged 18-40 years who were confirmed negative for H pylori infection were randomly assigned (3:4) to three intramuscular doses of either placebo or vaccine at 0, 1, and 2 months. Randomisation was via a computer-generated list with study numbers ensuring the correct ratio within a block size of seven. Participants were consecutively assigned in a double-blind manner to existing study numbers of the study protocol. Investigators and participants were blinded to allocation throughout the study. One month after the third immunisation, participants underwent challenge with a CagA-positive H pylori strain, which, for safety reasons, was initially administered in a subset of participants. The primary efficacy outcome was the efficacy of the vaccine as measured by the proportion of participants infected with H pylori 12 weeks after the challenge. At the end of the study, participants infected with H pylori were treated for 14 days with combination therapy consisting of a proton pump inhibitor and two antibiotics twice daily. Safety and immunogenicity were monitored at pre-established visits. This trial is registered with ClinicalTrials.gov, number NCT00736476, and is completed. FINDINGS: 63 patients were randomly assigned, 27 to placebo and 36 to the vaccine. 34 participants (19 in the vaccinated group and 15 in the placebo group) underwent infectious challenge, all but one of whom experienced transient mild-to-moderate epigastric symptoms. 12 weeks after infectious challenge, six (32%) of 19 people in the vaccinated group and six (40%) of 15 people in the placebo group remained positive for H pylori. Eradication was successful in everyone who remained infected at 12 weeks. The geometric mean concentrations of antibodies specific to CagA (202 [95% CI 69-588] vs 4·73 [95% CI 1·41-16]; p=0·001), VacA (1469 [838-2577] vs 73 [39-138]; p=0·001), and NAP (208 [139-313] vs 8·01 [5·05-13]; p=0·001) were significantly higher in the vaccine group than in the placebo group 12 weeks after infectious challenge. INTERPRETATION: Compared with placebo, the vaccine did not confer additional protection against H pylori infection after challenge with a CagA-positive strain, despite increased systemic humoral responses to key H pylori antigens. The finding of spontaneous clearance of H pylori infection in more than half the participants in the placebo group is remarkable and suggests important immune protection in the healthy adult population. FUNDING: Novartis Vaccine and Diagnostics.


Assuntos
Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Gastrite/prevenção & controle , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/imunologia , Imunogenicidade da Vacina , Adulto , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/efeitos adversos , Quimiocina CXCL1/imunologia , Método Duplo-Cego , Feminino , Gastrite/microbiologia , Humanos , Imunidade Celular , Imunoglobulina G/sangue , Injeções Intramusculares , Masculino , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Adulto Jovem
14.
Toxicol Appl Pharmacol ; 350: 64-77, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29751049

RESUMO

Most of the associated pathologies in Gulf War Illness (GWI) have been ascribed to chemical and pharmaceutical exposures during the war. Since an increased number of veterans complain of gastrointestinal (GI), neuroinflammatory and metabolic complications as they age and there are limited options for a cure, the present study was focused to assess the role of butyrate, a short chain fatty acid for attenuating GWI-associated GI and metabolic complications. Results in a GWI-mouse model of permethrin and pyridostigmine bromide (PB) exposure showed that oral butyrate restored gut homeostasis and increased GPR109A receptor copies in the small intestine (SI). Claudin-2, a protein shown to be upregulated in conditions of leaky gut was significantly decreased following butyrate administration. Butyrate decreased TLR4 and TLR5 expressions in the liver concomitant to a decrease in TLR4 activation. GW-chemical exposure showed no clinical signs of liver disease but a significant alteration of metabolic markers such as SREBP1c, PPAR-α, and PFK was evident. Liver markers for lipogenesis and carbohydrate metabolism that were significantly upregulated following GW chemical exposure were attenuated by butyrate priming in vivo and in human primary hepatocytes. Further, Glucose transporter Glut-4 that was shown to be elevated following liver complications were significantly decreased in these mice after butyrate administration. Finally, use of TLR4 KO mice completely attenuated the liver metabolic changes suggesting the central role of these receptors in the GWI pathology. In conclusion, we report a butyrate specific mechanistic approach to identify and treat increased metabolic abnormalities in GWI veterans with systemic inflammation, chronic fatigue, GI disturbances, metabolic complications and weight gain.


Assuntos
Butiratos/uso terapêutico , Modelos Animais de Doenças , Gastrite/metabolismo , Microbioma Gastrointestinal/fisiologia , Hepatócitos/metabolismo , Síndrome do Golfo Pérsico/metabolismo , Animais , Butiratos/farmacologia , Células Cultivadas , Técnicas de Reprogramação Celular/métodos , Gastrite/induzido quimicamente , Gastrite/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Humanos , Inseticidas/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Permetrina/toxicidade , Síndrome do Golfo Pérsico/induzido quimicamente , Síndrome do Golfo Pérsico/prevenção & controle
15.
Neuro Endocrinol Lett ; 39(1): 19-25, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29604620

RESUMO

OBJECTIVE: Papaya and oats are natural food and used in traditional medicine in many parts of the world. Papaya has a high content of enzymes supporting digestive function. Oats are a source of minerals, beta-glucan fibres, immunmodulatory and antiinflammatory probiotic substances. Caricol®-Gastro combines both constituents, it was designed as vegan organic preparation for intestinal inflammatory diseases. We performed a randomized, double blind placebo controlled clinical trial to investigate the potential of Caricol®-Gastro as add on therapy in patients with diagnosed chronic gastritis. METHODS: 60 Patients with endoscopically confirmed mild chronic disease were recruited. A structured interview documented the baseline data. Then the patients were allocated to the verum or placebo group by handing out a numbered study package with the study substance for the daily intake at home. A single dose was 20 g, taken twice per day. After 30 days the participants were interviewed again. RESULTS: After the intake phase the disease related symptoms were found improved in both groups, indicating a strong placebo effect. However, the pain load reduction in the Caricol®-Gastro group was significantly larger (p=0.048). DISCUSSION: Due to the inherent biological activities of ingredients of papaya and of oats and their known effects (anti-inflammatory, epithelial integrity), the observed beneficial effects may be owed to the constituents synergisms to reduce chronic inflammation. We conclude, that the regular intake is a safe add on therapeutic option for patients with chronic gastritis to support standard medical care.


Assuntos
Avena , Carica , Suplementos Nutricionais , Gastrite/complicações , Gastrite/prevenção & controle , Dor/etiologia , Dor/prevenção & controle , Probióticos/uso terapêutico , Adolescente , Adulto , Idoso , Avena/efeitos adversos , Carica/efeitos adversos , Doença Crônica , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Qualidade de Vida , Adulto Jovem
16.
Korean J Gastroenterol ; 71(3): 132-142, 2018 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-29566474

RESUMO

Background/Aims: Several lines of evidence from epidemiologic and laboratory studies have shown that the consumption of Artemisia or green tea extracts (MPGT) is inversely associated with the risk of alcohol-induced damage and other chronic diseases. Supported by previous studies showing that the combined extract of Artemisia and green tea, MPGT, exerted significantly either antioxidative or anti-inflammatory actions against Helicobacter pylori-associated gastric diseases, it was hypothesized that MPGT can offer protection against alcoholic gastritis. Methods: Ethanol was administered to induce gastric damage in Wistar rats, which had been pretreated with various doses of MPGT, to measure the rescuing action of a MPGT pretreatment against ethanol-induced gastric damage. In addition, the molecular mechanisms for the preventive effects were examined. Results: The MPGT pretreatment (100, 300, and 500 mg/kg) alleviated the ethanol-induced gastric damage, which was evidenced by the significant decrease in calcium-dependent phospholipase A2, MAPKs, and NF-κB levels compared to ethanol alone. Furthermore, the MPGT pretreatment preserved 15-prostaglandin dehydrogenase, whereas cyclooxygenase-2 was decreased significantly. All of these biochemical changes led to the significant alleviation of alcohol-associated gastric mucosal damage. Ethanol significantly increased the TUNEL positivity in the stomach, but MPGT decreased the apoptotic index significantly, which was associated with significantly lower pathological scores of ethanol-induced mucosal ulcerations. The significant protective changes observed alcoholic gastritis with MPGT were related to the increased expression of cytoprotective genes, such as heat-shock protein (HSP)27, HSP60, and PDGF. Conclusions: The efficient anti-inflammatory, anti-apoptotic, and regenerative actions of MPGT make it a potential nutrient phytoceutical to rescue the stomach from alcoholic gastritis.


Assuntos
Artemisia/química , Gastrite/prevenção & controle , Proteínas de Choque Térmico HSP27/metabolismo , Extratos Vegetais/farmacologia , Chá/química , Animais , Artemisia/metabolismo , Ciclo-Oxigenase 2/metabolismo , Etanol/toxicidade , Mucosa Gástrica/patologia , Gastrite/induzido quimicamente , Gastrite/patologia , Gastrite/veterinária , Proteínas de Choque Térmico HSP27/genética , Masculino , NF-kappa B/metabolismo , Fosfolipases A2/metabolismo , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Ratos , Ratos Wistar , Chá/metabolismo , Regulação para Cima/efeitos dos fármacos
17.
J Ethnopharmacol ; 216: 239-250, 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29410309

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori, which is found in the stomachs of approximately half of the world's population, has been associated with the development of chronic gastritis and gastric cancer. Hwanglyeonhaedok-tang (HHT) is a popular traditional medicine for the therapies of gastric ulcers and gastritis. AIM OF THE STUDY: The emerging resistance of H. pylori to antibiotics arouses requirement on alternative nonantibiotic-based therapies. In the present study, we investigated the anti-inflammatory activity and anti-microbial activity of HHT against H. pylori in vitro and in an H. pylori-infected mouse model. MATERIALS AND METHODS: H. pylori were treated with various concentrations of HHT and then incubated with human gastric carcinoma AGS cells. For the in vivo study, mice were orally infected with H. pylori three times over the course of 1 week, and then subjected to daily administration of HHT (120 or 600 mg/kg) for 4 weeks or standard triple therapy for 1 week. At the scheduled termination of the experiment, all mice were killed and their stomachs were collected for histological examination, quantitative real-time PCR, and Western blot analysis. RESULTS: Our in vitro studies showed that HHT treatment inhibited the adhesion of H. pylori to AGS cells and suppressed the H. pylori-induced increases of inflammatory regulators, such as interleukin (IL)-8, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). In the mouse model, HHT treatment significantly reduced H. pylori colonization, inflammation, and the levels of IL-1ß, IL-6, C-X-C motif chemokine ligand 1 (CXCL1), tumor necrosis factor alpha (TNF-α), COX-2, and iNOS in gastric mucosa. Further investigation showed that HHT treatment reduced the H. pylori-induced phosphorylations of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK), and nuclear factor-kappa B (NF-κB). CONCLUSIONS: Our findings collectively suggest that HHT has anti-inflammatory activity and antibacterial activity against H. pylori and could be an alternative to antibiotics for preventing H. pylori infection.


Assuntos
Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Gastrite/prevenção & controle , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estômago/efeitos dos fármacos , Animais , Aderência Bacteriana/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Mucosa Gástrica/metabolismo , Gastrite/metabolismo , Gastrite/microbiologia , Gastrite/patologia , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Estômago/microbiologia , Estômago/patologia
18.
World J Gastroenterol ; 23(34): 6350-6356, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28974902

RESUMO

AIM: To identify which technique is better for avoiding biliary reflux and gastritis between uncut Roux-en-Y and Billroth II reconstruction. METHODS: A total of 158 patients who underwent laparoscopy-assisted distal gastrectomy for gastric cancer at the First Hospital of Jilin University (Changchun, China) between February 2015 and February 2016 were randomized into two groups: uncut Roux-en-Y (group U) and Billroth II group (group B). Postoperative complications and relevant clinical data were compared between the two groups. RESULTS: According to the randomization table, each group included 79 patients. There was no significant difference in postoperative complications between groups U and B (7.6% vs 10.1%, P = 0.576). During the postoperative period, group U stomach pH values were lower than 7 and group B pH values were higher than 7. After 1 year of follow-up, group B presented a higher incidence of biliary reflux and alkaline gastritis. However, histopathology did not show a significant difference in gastritis diagnosis (P = 0.278), and the amount of residual food and gain of weight between the groups were also not significantly different. At 3 mo there was no evidence of partial recanalization of uncut staple line, but at 1 year the incidence was 13%. CONCLUSION: Compared with Billroth II reconstruction, uncut Roux-en-Y reconstruction is secure and feasible, and can effectively reduce the incidence of alkaline reflux, residual gastritis, and heartburn. Despite the incidence of recanalization, uncut Roux-en-Y should be widely applied.


Assuntos
Refluxo Biliar/epidemiologia , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Gastrite/epidemiologia , Gastroenterostomia/efeitos adversos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Neoplasias Gástricas/cirurgia , Idoso , Refluxo Biliar/etiologia , Refluxo Biliar/prevenção & controle , China/epidemiologia , Estudos de Viabilidade , Feminino , Gastrectomia/métodos , Derivação Gástrica/métodos , Gastrite/etiologia , Gastrite/patologia , Gastrite/prevenção & controle , Gastroenterostomia/métodos , Humanos , Incidência , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Reconstrutivos/métodos , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/patologia , Resultado do Tratamento
19.
Pharm Biol ; 55(1): 2110-2115, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28874080

RESUMO

CONTEXT: Aloe has been used for the prevention and cure of various diseases and symptoms including burns, injuries, oedema and pain. OBJECTIVE: This study determines the specific inhibitory activity of matrix metalloproteinase (MMP)-9 induced by the low molecular-weight gel fraction of Aloe vera (L.) Burm.f. (lgfAv) on alcohol-induced acute gastric lesions. MATERIALS AND METHODS: We examined the protective effects of oral (p.o.) administration of lgfAv (molecular weight cutoff <50.0 kDa, 150.0 mg/kg body weight) in a Balb/c mouse model of alcohol-induced acute gastritis for 1 h exposure. By measuring ulcer index, we compared the antiulcerative activity of the fraction. mRNA expression and immunohistochemical analysis of various biomarkers were performed. RESULTS: The lgfAv-treated mice exhibited drastically fewer ulcer lesions than the untreated control mice did. It featured that lgfAv lessened the ulcer lesions than their relevant controls. Moreover, the transcriptional level of MMP-9 was completely alleviated by lgfAv treatment in alcohol-treated gastritis-induced mice. DISCUSSION: The transcriptional level of MMP-9 was significantly alleviated by lgfAv treatment of the model. However, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry experiments revealed that lgfAv treatment in mucosal tissues had the potential to inhibit the mRNA and protein expression levels of MMP-9, respectively. The protein expression of MMP-9 was closely associated with lgfAv-induced gastroprotection against alcohol-induced gastric lesions. CONCLUSIONS: The present findings suggest that lgfAv has the potential to alleviate alcohol-induced acute gastric lesions, which is mediated in part, mainly by the suppression of the mRNA expression of MMP-9.


Assuntos
Aloe , Etanol/toxicidade , Metaloproteinase 9 da Matriz/biossíntese , Extratos Vegetais/uso terapêutico , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/prevenção & controle , Animais , Indução Enzimática/efeitos dos fármacos , Indução Enzimática/fisiologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/enzimologia , Gastrite/induzido quimicamente , Gastrite/enzimologia , Gastrite/prevenção & controle , Géis , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Úlcera Gástrica/enzimologia
20.
PLoS One ; 12(7): e0181546, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28742114

RESUMO

Hericium erinaceus (HE) has been used both as a traditional Chinese medicine and home remedy for treatment of gastric and duodenal ulcers and gastritis. EP-1, a purified polysaccharide isolated from HE mycelium, has recently been identified as the active component responsible for HE anti-gastritis activity. Because oxidative stress has been implicated as a pathogenic cause of gastritis and gastric ulcers, EP-1 antioxidant properties were systematically examined in vitro using the human gastric mucosal epithelial cell line, GES-1. Results showed that EP-1 possessed higher oxygen radical absorbance capacity (ORAC) and 2-3 times higher ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide and hydroxyl radicals than a hot water extract of commercially available HE fruiting body. A crude mycelial polysaccharide (CMPS) extract of HE, from which EP-1 was purified, showed slightly stronger radical scavenging activity and ORAC than EP-1, with the exception of DPPH-scavenging activity. Antioxidant activities of these extracts were further studied using hydrogen peroxide (H2O2)-abused GES-1 cells; EP-1 dose-dependently preserved cell viability of abused cells as assessed via MTT assay. Moreover, FACS analysis revealed that EP-1 prevented H2O2-induced apoptotic cell death by inhibiting activation of apoptotic cellular signals within mitochondria-dependent apoptotic pathways. CMPS also prevented H2O2-induced oxidative stress, but to a lesser degree than did EP-1, even though CMPS exhibited comparable or stronger in vitro antioxidant activity than did EP-1.


Assuntos
Antioxidantes/uso terapêutico , Basidiomycota/química , Mucosa Gástrica/efeitos dos fármacos , Gastrite/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/uso terapêutico , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite/metabolismo , Gastrite/patologia , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos , Micélio/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia
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