| In vitro |
Oral administration of Piceatannol significantly ameliorates structural damage to the colon in BALB/c mice with dextran sulfate sodium-induced colitis, markedly reducing the production of inflammatory mediators (such as nitric oxide, prostaglandin E2, and pro-inflammatory cytokines), and notably diminishes colonic myeloperoxidase (MPO) activity. In type 2 diabetic db/db mouse models, Piceatannol suppresses early elevation of blood glucose levels and improves impaired glucose tolerance in later stages.
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| In vivo |
In mast cells, Piceatannol is an effective inhibitor of histamine release, selectively suppressing Syk to block receptor-mediated cellular responses, including inhibition of 1,4,5-IP3 secretion, synthesis, membrane ruffling, and transportation. Piceatannol inhibits Syk activity approximately tenfold more potently than Lyn. When RBL-2H3 cells are treated with Piceatannol, antigen-stimulated phosphorylation of Syk and most other cellular proteins is strongly inhibited. However, it doesn’t affect the phosphorylation of receptor gamma or beta subtypes, presenting a dose-dependent inhibition. Piceatannol also effectively inhibits CDPK, MLCK, PKC, and PKA, with IC50 values of 19 μM, 12 μM, 8 μM, and 3 μM respectively. It selectively inhibits IFNα-induced tyrosine phosphorylation of STAT3/5 without affecting STAT1/2 and selectively inhibits the dephosphorylation of tyrosine on Jak1 and IFNAR1, not affecting Tyk2 and IFNAR2. Piceatannol induces apoptosis in BJAB Burkitt-like lymphoma cells via the activation of caspase-3 and changes in mitochondrial permeability, with an ED50 of 25 μM, independent of the CD95/Fas signaling pathway. It inhibits NF-κB activation induced by TNF, H2O2, PMA, lipopolysaccharides, okadaic acid, and ceramide. Specifically, it inhibits TNF-induced expression of NF-κB-dependent reporter genes (matrix metalloproteinase-9, cyclooxygenase-2, and cyclin D1) by blocking TNF-induced IκBαof phosphorylation, p65 nuclear translocation, and IκB kinase activation, independent of tyrosine kinase. Piceatannol binds to intracellular phosphatidylinositol kinase in an ATP-competitive manner, inhibiting its activity and exhibiting anti-atherosclerotic effects superior to resveratrol. Lastly, Piceatannol suppresses the proliferation of both androgen-dependent and -independent CaP cells and notably reduces the expression of mTOR and its key effectors AKT and eIF4EBP-1.
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