Ishophloroglucin A, a potent PTP1B inhibitor isolated from brown alga Ishige okamurae inhibits adipogenesis in 3T3-L1 adipocytes

Abstract

Ishophloroglucin A (IPA) is one of the most abundant and active compounds in Ishige okamurae and is known to be a potential therapeutic candidate for the improvement of metabolic diseases. However, IPA on the inhibitory effects of protein tyrosine phosphatase 1B (PTP1B) and adipogenesis have not been determined. In this study, we investigated the effects of IPA on the inhibition of PTP1B, the effects on adipogenesis, and its mechanisms of action in 3 T3-L1 adipocytes. The IC50 value of IPA against PTP1B was 0.43 mu M, which evidenced the higher inhibition activity than that of ursolic acid, a known PTP1B inhibitor. For further insight, we predicted the 3D structure of PTP1B and used a docking algorithm to simulate the binding between PTP1B and IPA. Molecular docking studies revealed a high and stable binding affinity between IPA and PTP1B and indicated that the IPA could interacts with the amino acid residues located in a region to the active site of PTP1B. Further studies showed that IPA concentrations between 6.25 mu M and 25 mu M dose-dependently attenuated adipogenesis, which was accompanied by a reduction in adipogenesis-related factors, including PPAR gamma, C/EBP alpha, SREBP-1c, and FABP4. Our findings suggested that IPA may be a promising natural compound for the treatment of obesity and related diseases.