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

• Published in: Archives of pharmacal research 2017, 40(1), , pp.37-48
• Main Authors: Jung, Hyun Ah, Ali, Md. Yousof, Bhakta, Himanshu Kumar, Min, Byung-Sun, Choi, Jae Sue
• Format: Article
• Language: English
• Subjects: Dose-Response Relationship, Drug; Flavonoids - chemistry; Flavonoids - isolation & purification; Flavonoids - pharmacology; Glucose - metabolism; Hep G2 Cells; Humans; Insulin Resistance - physiology; Medicine; Pharmacology/Toxicology; Pharmacy; Phlorhizin - analogs & derivatives; Phlorhizin - chemistry; Phlorhizin - isolation & purification; Phlorhizin - pharmacology; Plant Stems; Protein Structure, Secondary; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - antagonists & inhibitors; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Prunus; Research Article; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-016-0852-3

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 IC 50 value of 5.5 ± 0.29 µM, and significant inhibitory activity against α-glucosidase, with an IC 50 value of 317 ± 2.12 µM. Moreover, a kinetics study revealed that prunin inhibited PTP1B ( K i  = 8.66) and α-glucosidase ( K i  = 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.