PTP1B inhibitors from the seeds of Iris sanguinea and their insulin mimetic activities via AMPK and ACC phosphorylation

Jun Li Yang; Thi Kim Quy Ha; Ba Wool Lee; Jinwoong Kim; Won Keun Oh

doi:10.1016/j.bmcl.2017.09.031

PTP1B inhibitors from the seeds of Iris sanguinea and their insulin mimetic activities via AMPK and ACC phosphorylation

Bioorg Med Chem Lett. 2017 Nov 15;27(22):5076-5081. doi: 10.1016/j.bmcl.2017.09.031. Epub 2017 Sep 14.

Authors

Jun Li Yang¹, Thi Kim Quy Ha¹, Ba Wool Lee¹, Jinwoong Kim¹, Won Keun Oh²

Affiliations

¹ Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
² Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: [email protected].

PMID: 28951079
DOI: 10.1016/j.bmcl.2017.09.031

Abstract

To find PTP1B inhibitors from natural products, two new compounds (1 and 2), along with nine known compounds (3-11), were isolated from a methanol-soluble extract of Iris sanguinea seeds. The structures of compounds 1 and 2 were determined based on extensive spectroscopic data analysis including UV, IR, NMR, and MS. The IC₅₀ value of compound 5 on protein tyrosine phosphatase 1B (PTP1B) inhibitory activity is 7.30±0.88µM with a little activity compared to the IC₅₀ values of the tested positive compound. Compound 5 significantly enhanced glucose uptake and activation of pACC, pAMPK and partially Erk1/2 signaling. These results suggest that compound 5 from Iris sanguinea seeds are utilized as both PTP1B inhibitors and regulators of glucose uptake. These beneficial effects could be applied to treat metabolic diseases such as diabetes and obesity.

Keywords: AMPK; Glucose uptake; Iris sanguinea; PTP1B; Triterpene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

AMP-Activated Protein Kinases / metabolism*
Acetyl-CoA Carboxylase / metabolism*
Animals
Binding Sites
Biological Products / chemistry*
Biological Products / isolation & purification
Biological Products / pharmacology
Cell Line
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Glucose / metabolism
Insulins / chemistry
Iris / chemistry*
Iris / metabolism
Magnetic Resonance Spectroscopy
Mice
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Molecular Conformation
Molecular Docking Simulation
Phosphorylation / drug effects
Plant Extracts / chemistry
Protein Structure, Tertiary
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Seeds / chemistry
Seeds / metabolism
Signal Transduction / drug effects

Substances

Biological Products
Enzyme Inhibitors
Insulins
Plant Extracts
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
AMP-Activated Protein Kinases
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Acetyl-CoA Carboxylase
Glucose