Cyanidin 3-arabinoside

Cyanidin 3-arabinoside (CAS 27214-72-8) has protein tyrosine phosphatase 1B (PTP1B, a key therapeutic target for type 2 diabetes) as its core target. It exhibits significant inhibitory activity against PTP1B with an IC50 of 8.91±0.63μM, which is far superior to that of the positive control oleanolic acid (OA (Cata.NO.N1826), IC50=13.9±1.01μM). Meanwhile, it shows high selectivity over the homologous enzyme T-cell protein tyrosine phosphatase (TC-PTP, IC50=81.8±4.78μM ). Its mechanism of action is reversible mixed-type inhibition: it forms hydrogen bonds and hydrophobic interactions with residues such as Tyr46, Val49, and Cys215 near the PTP1B active pocket to block enzymatic activity, thereby downregulating the mRNA and protein expression of PTP1B, improving the IRS1/PI3K/Akt/GSK3β signaling pathway to promote glycogen synthesis. At high concentrations (>20μM), it can also activate the AMPK pathway to enhance insulin sensitivity. Additionally, it exerts a strong synergistic inhibitory effect with OA (combination index CI≤0.54; when used in combination at 20μM each, the PTP1B inhibition rate reaches 66%, exceeding the effect of either drug alone). At the cellular level, it dose-dependently promotes glucose consumption in HepG2 cells (the consumption rate reaches 43.6% at 40μM, close to that of metformin (57.4% at 10μM)), can restore glycogen content in PTP1B-overexpressing cells, and has good safety with a cell viability of >84% in HepG2 cells at 40μM, making it a potential dietary supplement or drug lead for type 2 diabetes.

References:

[1] Tian JL, Liao XJ, Wang YH, Si X, Shu C, Gong ES, Xie X, Ran XL, Li B. Identification of Cyanidin-3-arabinoside Extracted from Blueberry as a Selective Protein Tyrosine Phosphatase 1B Inhibitor. J Agric Food Chem. 2019 Dec 11;67(49):13624-13634. doi: 10.1021/acs.jafc.9b06155. Epub 2019 Dec 3. Erratum in: J Agric Food Chem. 2022 Feb 16;70(6):2060. doi: 10.1021/acs.jafc.2c00749. PMID: 31743023.