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1.
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
2.
PLoS One ; 15(7): e0236511, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32722717

RESUMO

The severe side effects of chemosynthetic anti-diarrhea drugs have created an interest in low-toxic alternative plant-derived compounds. FengLiao consists of Polygonum hydropiper Linn. and Daphniphyllum calycinum Bench., and is widely used in China to treat diarrhea due to low levels of toxicity. In this study, the effects of FengLiao were analyzed in a castor oil-induced diarrhea model, using the anti-diarrhea drug, loperamide, as the positive control. The effects were evaluated using stool characteristics and the expression levels of various diarrhea-related factors in the jejunum and liver, as well as changes in the microbiota of the jejunum. The symptoms of diarrhea and stool consistency were improved through FengLiao and loperamide treatment. Furthermore, FengLiao down-regulated alpha 1-acid glycoprotein (AGP) and C-reactive protein (CRP) levels, and up-regulated transferrin (TRF) mRNA levels in the liver, and down-regulated Aquaporin 3 (AQP3) and Na+/H+ exchanger isoform 8 (NHE8) expression in the epithelial cells of the jejunum. It also increased the relative abundance of Bifidobacterium, Aerococcus, Corynebacterium_1 and Pseudomonas, and lowered the Firmicutes/Bacteroidetes (F/B) ratio, which maintained the balance between immunity and intestinal health. Taken together, FengLiao alleviated castor oil-induced diarrhea by altering gut microbiota, and levels of jejunum epithelial transport proteins and acute phase proteins.


Assuntos
Proteínas de Fase Aguda/genética , Aquaporinas/genética , Diarreia/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Trocadores de Sódio-Hidrogênio/genética , Animais , Óleo de Rícino/toxicidade , Daphniphyllum/química , Diarreia/genética , Diarreia/microbiologia , Medicamentos de Ervas Chinesas/uso terapêutico , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/microbiologia , Camundongos , Polygonum/química
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