PDF(Pubmed)
Abstract：
The current study intended to investigate the role of new natural compounds derived from the Sesuvium sesuvioides plant in mitigating symptoms of diabetes and insulin resistance in the diabetic mice model. Anti-advanced glycation activity, insulin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Glucose uptake was performed using enzymatic fluorescence assay, and glycogen synthesis was measured using PAS staining. Gene and protein expression was assessed using real time PCR (RT-PCR), and immunoblotting and fluorescent microscopy, respectively. The new flavonoid glycoside eupalitin 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside 1 isolated from S. sesuvioides exhibited anti-AGE activity by reducing human glycated albumin in liver cells. In a diabetic mouse model treated with compound 1, we observed improved glucose tolerance, increased adiponectin levels, and decreased insulin resistance. We also observed alleviated AGEs induced reduction in glucose uptake and restored glycogen synthesis in the compound 1-treated diabetic mice muscles. Exploring the molecular mechanism of action in skeletal muscle tissue of diabetic mice, we found that 1 reduced AGE-induced reactive oxygen species and the inflammatory gene in the muscle of diabetic mice. Additionally, 1 exhibited these effects by reducing the gene and protein expression of receptor for advanced glycation end products (RAGE) and inhibiting protein kinase C (PKC) delta activation. This further led us to demonstrate that compound 1 reduced serine phosphorylation of IRS-1, thereby restoring insulin sensitivity. We conclude that a new flavonoid glycoside from S. sesuvioides could be a therapeutic target for the treatment of symptoms of insulin resistance and diabetes.
摘要：
本研究旨在研究源自Sesuvioides植物的新天然化合物在减轻糖尿病小鼠模型中的糖尿病症状和胰岛素抵抗中的作用。抗晚期糖基化活性，胰岛素，通过酶联免疫吸附测定（ELISA）定量和脂联素。使用酶荧光测定法进行葡萄糖摄取，使用PAS染色测量糖原合成。使用实时PCR(RT-PCR)评估基因和蛋白质表达,免疫印迹和荧光显微镜，分别。从S.sesuvioides中分离的新的类黄酮糖苷eupalitin3-O-α-L-鼠李糖吡喃-（1→2）-β-D-吡喃葡萄糖苷1通过减少肝细胞中的人糖化白蛋白而表现出抗AGE活性。在用化合物1治疗的糖尿病小鼠模型中，我们观察到葡萄糖耐量改善，脂联素水平升高，胰岛素抵抗降低。我们还在化合物1处理的糖尿病小鼠肌肉中观察到缓解的AGEs诱导的葡萄糖摄取减少和糖原合成恢复。探讨糖尿病小鼠骨骼肌组织的分子作用机制,我们发现1减少了糖尿病小鼠肌肉中AGE诱导的活性氧和炎症基因。此外,图1所示的实施例通过降低晚期糖基化终产物(RAGE)受体的基因和蛋白质表达并抑制蛋白激酶C(PKC)δ活化而表现出这些作用。这进一步导致我们证明化合物1降低IRS-1的丝氨酸磷酸化,从而恢复胰岛素敏感性。我们得出的结论是，来自S.sesuvioides的一种新的类黄酮糖苷可能是治疗胰岛素抵抗和糖尿病症状的治疗靶标。
