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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

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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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Authors and Affiliations

  1. Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea

    Hyun Ah Jung

  2. Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea

    Md. Yousof Ali, Himanshu Kumar Bhakta & Jae Sue Choi

  3. College of Pharmacy, Catholic University of Daegu, Gyeongsan, 712-702, Republic of Korea

    Byung-Sun Min

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  1. Hyun Ah Jung
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  2. Md. Yousof Ali
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Correspondence to Jae Sue Choi.

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Jung, H.A., Ali, M.Y., Bhakta, H.K. et al. 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. Arch. Pharm. Res. 40, 37–48 (2017). https://doi.org/10.1007/s12272-016-0852-3

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