Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2017-12-06 , DOI: 10.1016/j.cbi.2017.12.007 Ashok K. Singh , Vinit Raj , Amit K. Keshari , Amit Rai , Pranesh Kumar , Atul Rawat , Biswanath Maity , Dinesh Kumar , Anand Prakash , Arnab De , Amalesh Samanta , Bolay Bhattacharya , Sudipta Saha
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.
中文翻译:
隔离芒果苷,柚皮素使出通过PPAR抗糖尿病作用γ / GLUT4双重激动作用具有很强的代谢调控
在这项研究中,我们从长相思叶中分离了两种化合物(SA1,芒果苷和SA2,柚皮苷)及其结构通过红外光谱,核磁共振(NMR)光谱和质谱法确定。每天以50和100 mg / kg的剂量口服SA1和SA2口服链脲佐菌素诱导的糖尿病大鼠,持续15天。进行了血糖水平,血清脂质谱,氧化应激参数,组织病理学,对接,分子参数和基于NMR的代谢扰动研究,以研究SA1和SA2的药理活性。结果表明这两种化合物均降低了血糖水平,恢复了体重,并使血清中的脂质浓度和肝脏和胰腺中的氧化应激生物标志物正常化。此外,γ)和4型葡萄糖转运蛋白(GLUT4)。进行进一步的实时逆转录-聚合酶链反应和Western印迹分析来确认PPAR的基因和蛋白表达水平γ在胰腺组织和GLUT4。从分子研究的数据获得的表明,两种化合物显示出通过PPAR的双重激活抗糖尿病作用γ / GLUT4信号通路。最后,基于NMR的代谢研究表明这两种化合物均能使血清中的糖尿病形成代谢产物正常化。总之,我们得出结论,SA1和SA2可能是未来药物开发的潜在抗糖尿病先导化合物。