RESUMO
Hyperglycemia is associated with advanced glycation end products (AGEs). Recently, AGEs were found to cause pancreatic damage, oxidative stress, and hyperglycemia through the AGE receptor. Carboxymethyllysine (CML) is an AGE but whether it induces pancreatic dysfunction remains unclear. Graptopetalum paraguayense, a vegetable consumed in Taiwan, has been used in folk medicine and is an antioxidant that protects against liver damage. We investigated the protective properties of G. paraguayense 95% ethanol extracts (GPEs) against CML-induced pancreatic damage. The results indicated that resveratrol, GPE, and gallic acid (the active compound of GPE) increased insulin synthesis via upregulation of pancreatic peroxisome proliferator activated-receptor-γ (PPARγ) and pancreatic-duodenal homeobox-1 (PDX-1) but inhibited the expression of CML-mediated CCAAT/enhancer binding protein-ß (C/EBPß), a negative regulator of insulin production. Moreover, resveratrol and GPE also strongly activated nuclear factor-erythroid 2-related factor 2 (Nrf2) to attenuate oxidative stress and improve insulin sensitivity in the liver and muscle of CML-injected C57BL/6 mice and resulted in reduced blood glucose levels. Taken together, these findings suggested that GPE and gallic acid could potentially be used as a food supplement to protect against pancreatic damage and the development of diabetes.
Assuntos
Crassulaceae/química , Hiperglicemia/tratamento farmacológico , Lisina/análogos & derivados , Pâncreas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Estilbenos/farmacologia , Animais , Ácido Gálico/análise , Ácido Gálico/farmacologia , Proteínas de Homeodomínio/metabolismo , Hiperglicemia/induzido quimicamente , Hiperglicemia/fisiopatologia , Insulina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lisina/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Pâncreas/fisiopatologia , Resveratrol , Taiwan , Transativadores/metabolismoRESUMO
Role of inflammation-induced oxidative stress in the pathogenesis and progression of chronic inflammatory airways diseases has received increasing attention in recent years. Nuclear factor erythroid 2-related factor 2 is the primary transcription factor that regulates the expression of antioxidant and detoxifying enzymes. Graptopetalum paraguayense E. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury through elevating antioxidation. Recently, we found that gallic acid is an active compound of Graptopetalum paraguayense E. Walther, which has been reported to inhibit T-helper 2 cytokines. Currently, we assumed that Graptopetalum paraguayense E. Walther may potentially protect against ovalbumin-induced allergy and airway inflammation. Results demonstrated that Graptopetalum paraguayense E. Walther ethanolic extracts (GPE) clearly inhibited airway inflammation, mucus cell hyperplasia, and eosinophilia in OVA-challenged mice. Additionally, GPE also prevented T-cell infiltration and Th2 cytokines, including interleukin- (IL-)4, IL-5, and IL-13 generations in bronchial alveolar lavage fluid. The adhesion molecules ICAM-1 and VCAM-1 were substantially reduced by GPE treatment mediated by Nrf2 activation. Moreover, GPE attenuated GATA3 expression and inhibited Th2 signals of the T cells. These findings suggested that GPE ameliorated the development of airway inflammation through immune regulation.
RESUMO
AIM OF THIS STUDY: Graptopetalum paraguayense E. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. Therefore, we investigated the protective effects of Graptopetalum paraguayense E. Walther against carbon tetrachloride (CCl(4))-induced liver damage in rats. MATERIALS AND METHODS: Water extracts of Graptopetalum paraguayense E. Walther (WGP) were administered for 8 consecutive weeks to male Sprague-Dawley rats. And a dose-dependent manner in preventing liver damage was confirmed. Moreover, the major ingredient of WGP, gallic acid, was also orally administrated in the CCl(4)-induced rats. The hepatoprotective activity was assessed using various biochemical parameters such as antioxidant enzymes and histopathological studies. RESULTS: WGP ranging from 50 to 300 mg/kg bw administrations significantly lowered serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, and inhibited malondialdehyde (MDA) generation in CCl(4)-treated rats. WGP increased cellular GSH level and antioxidant enzymes, including superoxide dismutase, glutathione reductase, and catalase. Serum tumor necrosis factor-alpha (TNF-α) was decreased in the group treated with CCl(4) plus WGP (150 and 300 mg/kg bw). Histopathological examination of livers showed that WGP reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl(4)-treated rats. In contrary, 10mg/kg bw of gallic acid was administrated, this dose was related with WGP (300 mg/kg bw), and had significantly decreased the AST and ALT compared to the CCl(4)-treated group. Aforesaid results suggested that gallic acid from WGP offered antioxidative activity against CCl(4)-induced oxidative liver damage. CONCLUSIONS: Taken together, this study is the first time to suggest that Graptopetalum paraguayense E. Walther exerts hepatoprotection via promoting antioxidative and anti-inflammatory properties against CCl(4)-induced oxidative liver damage.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Crassulaceae/química , Ácido Gálico/uso terapêutico , Fígado/efeitos dos fármacos , Fitoterapia , Alanina Transaminase/sangue , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas/sangue , Relação Dose-Resposta a Droga , Ácido Gálico/farmacologia , Fígado/enzimologia , Fígado/patologia , Masculino , Malondialdeído/sangue , Medicina Tradicional , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Taiwan , Fator de Necrose Tumoral alfa/sangueRESUMO
Accumulation of bioactive compounds, during developmental stages of Graptopetalum paraguayense E. Walther, was investigated between 30 and 90days as a function of physiological maturity. Three distinct phases were defined: immature phase (30days), intermediate developmental phase (30-60days), and maturation phase (60-90days). Gallic acid and quercetin, antioxidative bioactive compounds, were identified as biomarkers for determining the optimum physiological maturity stage in G. paraguayense E. Walther. With regard to the antioxidant activity of G. paraguayense E. Walther at different developmental stages, the results indicated that the leaves of immature G. paraguayense E. Walther had the highest 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonate) (ABTS-), superoxide radical-, and 1,1-diphenyl-2-picrylhydrazyl (DPPH·)-scavenging activities. Fermentation of G. paraguayense E. Walther with Lactobacillus plantarum BCRC 10357 significantly increased the level of flavonoids and total phenolics, including quercetin and gallic acid. Total phenols were the major naturally occurring antioxidant components in lactic acid bacteria-fermented G. paraguayense E. Walther.