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.
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