Biomedical Research Center, Department of Biomedical & Biological Sciences, Sohail University, Karachi 78400, Pakistan.
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.
Molecules. 2024 Aug 1;29(15):3649. doi: 10.3390/molecules29153649.
The current study intended to investigate the role of new natural compounds derived from the 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--α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside isolated from exhibited anti-AGE activity by reducing human glycated albumin in liver cells. In a diabetic mouse model treated with compound , 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 -treated diabetic mice muscles. Exploring the molecular mechanism of action in skeletal muscle tissue of diabetic mice, we found that reduced AGE-induced reactive oxygen species and the inflammatory gene in the muscle of diabetic mice. Additionally, 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 reduced serine phosphorylation of IRS-1, thereby restoring insulin sensitivity. We conclude that a new flavonoid glycoside from could be a therapeutic target for the treatment of symptoms of insulin resistance and diabetes.
本研究旨在探讨从植物中提取的新型天然化合物在减轻糖尿病小鼠模型中糖尿病和胰岛素抵抗症状方面的作用。通过酶联免疫吸附测定(ELISA)定量测定抗糖基化活性、胰岛素和脂联素。使用酶荧光测定法进行葡萄糖摄取,使用 PAS 染色法测量糖原合成。使用实时 PCR(RT-PCR)、免疫印迹和荧光显微镜分别评估基因和蛋白质表达。从 中分离得到的新型黄酮糖苷 eupalitin 3--α-L-鼠李吡喃糖基-(1→2)-β-D-吡喃葡萄糖苷在肝细胞中通过降低人糖化白蛋白表现出抗 AGE 活性。在用化合物 治疗的糖尿病小鼠模型中,我们观察到葡萄糖耐量改善、脂联素水平升高和胰岛素抵抗降低。我们还观察到 AGE 诱导的葡萄糖摄取减少和糖原合成在化合物治疗的糖尿病小鼠肌肉中得到缓解。在糖尿病小鼠的骨骼肌组织中探索作用的分子机制,我们发现 减少了 AGE 诱导的活性氧和糖尿病小鼠肌肉中的炎症基因。此外, 通过降低晚期糖基化终产物(RAGE)受体的基因和蛋白表达并抑制蛋白激酶 C(PKC)δ激活来发挥这些作用。这进一步使我们能够证明化合物 减少 IRS-1 的丝氨酸磷酸化,从而恢复胰岛素敏感性。我们得出结论,来自 的新型黄酮糖苷可能是治疗胰岛素抵抗和糖尿病症状的治疗靶点。