Prunin is a highly potent flavonoid from Prunus davidiana stems that inhibits protein tyrosine phosphatase 1B and stimulates glucose uptake in insulin-resistant HepG2 cells
详细信息 查看全文
- 作者：Hyun Ah Jung ; Md. Yousof Ali ; Himanshu Kumar Bhakta…
- 关键词：Prunin ; Protein tyrosine phosphatase 1B ; Anti ; diabetic ; Glucose uptake ; HepG2 cell ; Molecular docking
- 刊名：Archives of Pharmacal Research
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：40
- 期：1
- 页码：37-48
- 全文大小：
- 刊物主题：Pharmacy; Pharmacology/Toxicology;
- 出版者：Pharmaceutical Society of Korea
- ISSN：1976-3786
- 卷排序：40
文摘
Prunin is the main flavonoid in Prunus davidiana stems and improves hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. The aim of this study was to investigate the in vitro anti-diabetic potential of prunin via the inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, peroxynitrite (ONOO−)-mediated tyrosine nitration, and stimulation of glucose uptake in insulin-resistant hepatocytes. In addition, a molecular docking simulation was performed to predict specific prunin binding modes during PTP1B inhibition. Prunin showed strong inhibitory activity against PTP1B, with an IC50 value of 5.5 ± 0.29 µM, and significant inhibitory activity against α-glucosidase, with an IC50 value of 317 ± 2.12 µM. Moreover, a kinetics study revealed that prunin inhibited PTP1B (Ki = 8.66) and α-glucosidase (Ki = 189.56) with characteristics typical of competitive and mixed type inhibitors, respectively. Docking simulations showed that prunin selectively inhibited PTP1B by targeting its active site and exhibited good binding affinity, with a docking score of −9 kcal/mol. Furthermore, prunin exhibited dose-dependent inhibitory activity against ONOO−-mediated tyrosine nitration and stimulated glucose uptake by decreasing PTP1B expression level in insulin-resistant HepG2 cells. These results indicate that prunin has significant potential as a selective PTP1B inhibitor and may possess anti-diabetic properties by improving insulin resistance.