RESUMO
BACKGROUND AND AIMS: Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, which occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension. Activated hepatic perivascular stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines, such as TGF-ß1. The inhibition of TGF-ß1 function or synthesis is a major target for the development of antifibrotic therapies. Our previous study showed that the water and ethanol extracts of Graptopetalum paraguayense (GP), a Chinese herbal medicine, can prevent dimethylnitrosamine (DMN)-induced hepatic inflammation and fibrosis in rats. METHODS: We used rat hepatic stellate HSC-T6 cells and a diethylnitrosamine (DEN)-induced rat liver injury model to test the potential mechanism of GP extracts and its fraction, HH-F3. RESULTS: We demonstrated that GP extracts and HH-F3 downregulated the expression levels of extracellular matrix (ECM) proteins and inhibited the proliferation and migration via suppression of the TGF-ß1 pathway in rat hepatic stellate HSC-T6 cells. Moreover, the HH-F3 fraction decreased hepatic collagen content and reduced plasma AST, ALT, and γ-GT activities in a DEN-induced rat liver injury model, suggesting that GP/HH-F3 has hepatoprotective effects against DEN-induced liver fibrosis. CONCLUSION: These findings indicate that GP/HH-F3 may be a potential therapeutic agent for the treatment of liver fibrosis. The inhibition of TGF-ß-mediated fibrogenesis may be a central mechanism by which GP/HH-F3 protects the liver from injury.
Assuntos
Crassulaceae/química , Cirrose Hepática/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Fator de Crescimento Transformador beta/metabolismo , Animais , Linhagem Celular , Colágeno/genética , Colágeno/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais , Fator de Crescimento Transformador beta/genéticaRESUMO
The fruiting body of Antrodia cinnamomea is used as a medicinal mushroom in Taiwan and is found on the inner cavity of the endemic species Cinnamomum kanehirai. In this study, phytomics similarity index (PSI) analysis was employed for the chemical quality evaluation of the A. cinnamomea fruiting bodies from different strains, and grown on various substrates. The results indicated that the different types of A. cinnamomea fruiting bodies contain eight index compounds, and that it was difficult to discriminate between them solely on the basis of those index compounds. In our research, we used PSI scores to assess the metabolite similarity of the fruiting bodies of A. cinnamomea. It was revealed that fruiting bodies from various A. cinnamomea strains grown on different culture substrates produce distinct PSI scores. We concluded that PSI analysis had good selectivity on the different types of A. cinnamomea fruiting bodies.