In vitro effects of cinnamic acid derivatives on protein tyrosine phosphatase IB

摘要

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 PTPIBs were o-hydroxycinnamic acid and p-hydroxycinnamic acid, which had IC_(50) values of 137.67(+-)13.37 and 181.60 (+-)9.34 uM, 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 uM) and p-hydroxycinnamic acid (25 uM), in combination with sodium orthovanadate (0.0125 uM), 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.