Protein tyrosine phosphatase 1B (PTP1B) is an important target for type 2 diabetes. PTP1B inhibitors can reduce blood glucose levels by increasing insulin sensitivity. Anthocyanins often play a hypoglycemic effect, but the research about them have mainly focused on glucosidase. At present, the research about protein tyrosine phosphatase 1B (PTP1B) target is less, and the corresponding molecular mechanism is still unclear. Therefore, in this present study, anthocyanins isolated from blueberry were used to study the inhibitory activity on PTP1B. The isolated cyanidin-3-arabinoside (Cya-3-Ara) exhibited a better inhibitory activity with IC50 = 8.91 ± 0.63 μM, which was higher than the positive control (oleanolic acid, IC50 = 13.9 ± 1.01 μM), and the mechanism of PTP1B inhibition was reversible mixed pattern. The structure-activity relationship (SAR) between anthocyanins and PTP1B inhibition was investigated. The enzyme activity inhibition and molecular docking showed that anthocyanins had high selectivity for PTP1B inhibition. Further study showed that Cya-3-Ara could promote glycogen synthesis through ameliorating PTP1B-involved IRS-1/PI3K/Akt/GSK3β pathways. Cya-3-Ara could also be regarded as a synergistic inhibitor (CI ≤ 0.54) of oleanolic acid to obtain a better inhibitory effect on PTP1B. Taken together, our study clearly illustrates the SAR between anthocyanins and PTP1B inhibition and the mechanism of Cya-3-Ara in the insulin signaling pathway.
Keywords: PTP1B; anthocyanins; hypoglycemic effect; molecular docking; synergistic inhibition.