Prunin is a highly potent flavonoid from <Emphasis Type="Italic">Prunus davidiana</Emphasis> stems that inhibits protein tyrosine phosphatase 1B and stimulates glucose uptake in insulin-resistant HepG2 cells |
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Authors: | Hyun Ah Jung Md Yousof Ali Himanshu Kumar Bhakta Byung-Sun Min Jae Sue Choi |
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Affiliation: | 1.Department of Food Science and Human Nutrition,Chonbuk National University,Jeonju,Republic of Korea;2.Department of Food and Life Science,Pukyong National University,Busan,Republic of Korea;3.College of Pharmacy,Catholic University of Daegu,Gyeongsan,Republic of Korea |
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Abstract: | 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 (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. |
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