In vitro effects of cinnamic acid derivatives on protein tyrosine phosphatase 1B

Abstract

Protein Tyrosine Phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling pathways. Finding selective PTP1B inhibitors from natural sources has been widely recognized as a potential drug target for the treatment of diabetes mellitus and obesity. In the present study, we evaluated the inhibitory activity of cinnamic acid derivatives against PTP1B in vitro. Among 14 cinnamic acid derivatives and related compounds, the most potent inhibitor PTP1Bs were o-hydroxycinnamic acid and p-hydroxycinnamic acid, which had IC₅₀ values of 137.67 ± 13.37 and 181.60 ± 9.34 µM, respectively. The kinetics analysis revealed that PTP1B was inhibited by o-hydroxycinnamic acid and p-hydroxycinnamic acid in a non-competitive manner. o-Hydroxycinnamic acid (25 μM) and p-hydroxycinnamic acid (25 μM), in combination with sodium orthovanadate (0.0125 μM), demonstrated a synergistic effect to inhibit PTP1B activity. In conclusion, the findings provide a new insight into naturally occurring PTP1B inhibitors that could be useful for treatment of diabetes and obesity.

Keywords::

• Cinnamic acid derivatives
• protein tyrosine phosphatase 1B
• kinetic inhibition
• synergism

Acknowledgments

We wish to thank the Faculty of Allied Health Sciences, Chulalongkorn University, for financial supporting this study. The authors would also like to thank The Medical Food Research and Development Center and The Research Group of Herbal Medicine for Prevention and Therapeutic of Metabolic diseases, which have been financially and institutionally supported by Chulalongkorn University.

Declaration of interest

The authors report no conflicts of interest.