RESUMO
In this study, we isolated two compounds from the leaves of Salacia oblonga (SA1, mangiferin and SA2, naringenin), and their structures were confirmed by infrared spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry. SA1 and SA2 were orally administered to streptozotocin-induced diabetic rats at 50 and 100 mg/kg daily for 15 days. Blood glucose level, serum lipid profile, oxidative stress parameters, histopathology, docking, molecular parameters, and NMR-based metabolic perturbation studies were performed to investigate the pharmacological activities of SA1 and SA2. Results suggested that both compounds reduced blood glucose level, restored body weight, and normalized lipid concentrations in the serum and oxidative stress biomarkers in the liver and pancreas. In addition, the docking study on several diabetes-associated targets revealed that both compounds had a strong binding affinity towards peroxisome proliferator-activated receptor gamma (PPARγ) and glucose transporter type 4 (GLUT4). Further real-time reverse transcription polymerase chain reaction and western blot analyses were performed to confirm the gene and protein expression levels of PPARγ and GLUT4 in the pancreatic tissues. Data obtained from the molecular studies showed that both compounds exhibited antidiabetic effects through dual activation of PPARγ/GLUT4 signaling pathways. Finally, the NMR-based metabolic studies showed that both compounds normalized the diabetogenic metabolites in the serum. Altogether, we concluded that SA1 and SA2 might be potential antidiabetic lead compounds for future drug development.
Assuntos
Flavanonas/farmacologia , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/farmacologia , PPAR gama/metabolismo , Xantonas/farmacologia , Animais , Glicemia/análise , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Flavanonas/isolamento & purificação , Flavanonas/uso terapêutico , Transportador de Glucose Tipo 4/agonistas , Transportador de Glucose Tipo 4/genética , Glicogênio/metabolismo , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/agonistas , PPAR gama/genética , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Estrutura Terciária de Proteína , Ratos , Salacia/química , Salacia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/toxicidade , Xantonas/isolamento & purificação , Xantonas/uso terapêuticoRESUMO
Thirteen triterpenoids (1-13), including two new lupane triterpenoids, salacinins A and B (1 and 2), as well as one new friedelane triterpenoid, salacinin C (3), were isolated from the roots and stems of Salacia hainanensis. The structures of new compounds were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, and MS experiments. Compound 1 possesses rare 2,3-seco-lupane skeleton. Compounds 4, 6 and 7 showed inhibitory effects on α-glucosidase in vitro.
