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Drug Des Devel Ther ; 15: 2629-2639, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168434

RESUMO

BACKGROUND: Acanthopanax trifoliatus (L.) Merr. is a medicinal plant found in Southeast Asia, and its young leaves and shoots are consumed as a vegetable. The main bioactive components of this herb are polysaccharides that have significant anti-diabetic effects. The aim of this study was to evaluate the immunoregulatory effect of A. trifoliatus (L.) Merr. polysaccharide (ATMP) on a mouse model of type 1 diabetes mellitus (T1DM). METHODS: The monosaccharide composition and mean molecular mass of ATMP were determined by HPLC and HPGPC. T1DM was induced in mice using STZ, and 35, 70 and 140mg/kg ATMP was administered daily via the intragastric route for six weeks. Untreated and metformin-treated positive control groups were also included. The body weight of the mice, food and water intake and fasting glucose levels were monitored throughout the 6-week regimen. Histological changes in the pancreas and spleen were analyzed by H&E staining. Oral glucose tolerance was evaluated with the appropriate test. Peroxisome proliferator-activated receptor γ (PPARγ) mRNA and protein levels in the spleen were measured by quantitative real time PCR and Western blotting. IL-10, IFN-γ and insulin levels in the sera were determined by ELISA. The CD4+ and CD8+T cells in spleen tissues were detected by immunohistochemistry (IHC). RESULTS: ATMP and metformin significantly decreased fasting blood glucose, and the food and water intake after 6 weeks of treatment. In contrast, serum insulin levels, glucose tolerance and body weight improved considerably in the high and medium-dose ATMP and metformin groups. T1DM was associated with pancreatic and splenic tissue damage. The high dose (140mg/kg) of ATMP reduced infiltration of inflammatory cells into the pancreas and restored the structure of islet ß-cells in the diabetic mice. Consistent with this, 35, 70 and 140mg/kg ATMP increased IL-10 levels and decreased that of IFN-γ, thereby restoring the CD4+/CD8+ and Th1/Th2 cytokine ratio. At the molecular level, high-dose ATMP up-regulated PPARγ in the splenic cells. CONCLUSION: ATMP exerts a hypoglycemic effect in diabetic mice by restoring the immune balance in the spleen.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Eleutherococcus/química , Polissacarídeos/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Tipo 1/imunologia , Teste de Tolerância a Glucose , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Masculino , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos/isolamento & purificação , Baço/efeitos dos fármacos , Baço/imunologia
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