RÉSUMÉ
In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .
Sujet(s)
Animaux , Souris , Adipocytes blancs/métabolisme , Ananas/composition chimique , Compléments alimentaires , Fruit/composition chimique , Hypoglycémiants/isolement et purification , Déchets industriels/analyse , Extraits de plantes/isolement et purification , Adipogenèse , Adipocytes blancs/cytologie , Antioxydants/composition chimique , Antioxydants/économie , Antioxydants/isolement et purification , Antienzymes/composition chimique , Antienzymes/économie , Antienzymes/isolement et purification , Industrie de la transformation des aliments/économie , Glycosylation , Glycerolphosphate dehydrogenase/antagonistes et inhibiteurs , Glycerolphosphate dehydrogenase/métabolisme , Inhibiteurs des glycoside hydrolases/composition chimique , Inhibiteurs des glycoside hydrolases/économie , Inhibiteurs des glycoside hydrolases/isolement et purification , Hypoglycémiants/composition chimique , Hypoglycémiants/économie , Inde , Déchets industriels/économie , Lipotropes/composition chimique , Lipotropes/économie , Lipotropes/isolement et purification , Extraits de plantes/composition chimique , Extraits de plantes/économie , Solvants/composition chimique , alpha-Amylases/antagonistes et inhibiteurs , alpha-Amylases/métabolismeRÉSUMÉ
BACKGROUND: Rapid urbanisation and nutritional transition is fuelling the increased global incidence of type 2 diabetes. Pineapple fruit residue was explored for its nutraceutical properties as an alternative or adjunct to currently available treatment regime. Ethyl acetate and methanolic extracts of pineapple fruit residue were evaluated for anti-diabetic activity in cell free and cell based systems. Specifically, we assessed: (1) antioxidant potential, (2) anti-glycation potential, (3) carbohydrate digestive enzyme inhibition, and (4) lipid accumulation and glycerol-3-phosphate dehydrogenase activity in differentiating 3T3-L1 cells. RESULTS: The active components in the ethyl acetate and methanolic extracts were identified as sinapic acid, daucosterol, 2-methylpropanoate, 2,5-dimethyl-4-hydroxy-3(2H)-furanone, methyl 2-methylbutanoate and triterpenoid ergosterol using DART/HRMS and ESI/HRMS. Micronutrient analysis revealed the presence of magnesium, potassium and calcium. Adipogenic potential, anti-glycation property of the ethyl acetate extract, and DNA damage protection capacity of the methanolic extract are promising. CONCLUSION: Results from this study clearly indicate that pineapple fruit residue could be utilised as a nutraceutical against diabetes and related complications.