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Natural Products and Type 2 Diabetes Prevention

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Front. Chem. | doi: 10.3389/fchem.2018.00040

Isolation and characterization of protein tyrosine phosphatase 1B (PTP1B) inhibitory polyphenolic compounds from Dodonaea viscosa and their kinetic analysis

 Zia Uddin1, Yeong Hun Song1, Mahboob Ullah1, Zuopeng Li1, Jeong Yoon Kim1 and  Ki Hun Park1*
  • 1Division of Applied Life Science (BK21 plus), IALS, Gyeongsang National University, South Korea

Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine (1-9) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC50 13.5-57.9 μM. Among them, viscosol (4) was found to be the most potent compound having IC50 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (Ki) value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7 and 9 were found to be the most abundant metabolites in D.viscosa extract.

Keywords: polyphenolic compounds, Dodonaea viscosa, PTP1B inhibition, enzyme kinetics., Diabetes Mellitus, Type 2

Received: 30 Nov 2017; Accepted: 14 Feb 2018.

Edited by:

Dejian Huang, National University of Singapore, Singapore

Reviewed by:

Marcin Szymański, Poznan University of Medical Sciences, Poland
Yuyun Lu, National University of Singapore, Singapore  

Copyright: © 2018 Uddin, Song, Ullah, Li, Kim and Park. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Ki Hun Park, Gyeongsang National University, Division of Applied Life Science (BK21 plus), IALS, Jinju, South Korea, khpark@gnu.ac.kr