title: 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.
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 IC50value of 5.5 ± 0.29 µM, and significant inhibitory activity against α-glucosidase, with an IC50value 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.
authors: Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
authors: Hyun Ah
authors: HA
authors: Jung
authors: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors: Md Yousof
authors: MY
authors: Ali
authors: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea.
authors: Himanshu Kumar
authors: HK
authors: Bhakta
authors: College of Pharmacy, Catholic University of Daegu, Gyeongsan, 712-702, Republic of Korea.
authors: Byung-Sun
authors: BS
authors: Min
authors: Department of Food and Life Science, Pukyong National University, Busan, 608-737, Republic of Korea. choijs@pknu.ac.kr.
authors: Jae Sue
authors: JS
authors: Choi
mesh_terms: D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D010695:Phlorhizin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D018547:Plant Stems; D017433:Protein Structure, Secondary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027861:Prunus
chemical_list: D005419:Flavonoids; C506622:prunin; D010695:Phlorhizin; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D005947:Glucose
keywords: Anti-diabetic; Glucose uptake; HepG2 cell; Molecular docking; Protein tyrosine phosphatase 1B; Prunin