Piceatannol (Astringenin) is an anti-inflammatory, immunomodulatory and antiproliferative agent. It inhibits p56lck and syk protein tyrosine kinases and inhibits NF-κB activation and gene expression of TNF-induced. It is synthetic from the conversion of resveratrol by cytochrome P450 1B1.

PKC:8 μM, CAK:3 μM, MLCK:12 μM

在肥大细胞中,Piceatannol是一种有效的组胺释放抑制剂。Piceatannol选择性抑制肥大细胞中的Syk从而阻断受体介导的下游细胞应答,包括对1,4,5-IP3分泌、合成,胞膜边缘波动以及运输的抑制。Piceatannol对Syk的抑制效果比对Lyn高10倍左右。RBL-2H3 细胞经Piceatannol处理后,抗原刺激的Syk和其它大部分细胞蛋白的磷酸化会受到强烈抑制,但对不影响受体γ或β亚型的磷酸化, 这种抑制呈剂量依赖性。Piceatannol也可以有效地抑制 CDPK,MLCK,PKC和PKA（IC50 分别为：19 μM,12 μM,8 μM,3 μM）。Piceatannol对IFNα诱导的 STAT3/5酪氨酸磷酸化具有选择性抑制作用, 但不影响STAT1/2, 同时对 Jak1 和 IFNAR1酪氨酸去磷酸化有选择性抑制作用,但不影响Tyk2和 IFNAR2。Piceatannol 通过激活半胱天冬酶3和线粒体通透性改变可以有效地诱导BJAB Burkitt样淋巴瘤细胞凋亡,ED50 为 25 μM,这一过程实现而不依赖CD95/Fas信号通路。Piceatannol抑制TNF, H2O2, PMA, 脂多糖, 冈田酸和神经酰胺诱导的NF-κB 激活。Piceatannol抑制TNF诱导的NF-κB依赖性报告基因（基质金属蛋白酶- 9, 环氧酶-2和 cyclin D1）表达,该过程通过阻断TNF诱导的IκBαof、p65磷酸化,p65核转位以及IκBα激酶激活实现,而不依赖酪氨酸激酶。 Piceatannol 通过三磷酸腺苷竞争性方式直接结合胞内磷脂酰肌醇激酶进而抑制酶活性,其抗硬化效果比resveratrol的抗动脉粥样更好。Piceatannol抑制雄激素依赖或不依赖的CaP 细胞增殖,同时能使mTOR和其关键效应器 AKT和eIF4EBP-1的表达明显下降。

在治疗患有葡聚糖硫酸钠诱导的BALB/c结肠炎小鼠模型时,口服给药Piceatannol会明显改善结肠结构破坏情况,明显减少炎症介质产生量（如一氧化氮, 前列腺素E2和前炎症细胞因子）,并且会引起结肠髓MPO活性明显降低.在2型糖尿病db/db 小鼠模型中,Piceatannol会抑制早期血糖水平的升高,在晚期可以改善糖耐量受损症状.

In Vitro Protein-tyrosine Kinase Assays: Recombinant Syk is expressed in baculovirus-infected St9 cells. Assays of recombinant Syk activity are carried out using angiotensin I peptide as substrate. The enzyme activities of recombinant Syk are measured by phosphorylation of angiotensin I peptide in the presence of various concentrations of Piceatannol.

Cells are exposed to increasing concentrations of Piceatannol. For the determination of cell proliferation, cells are assayed at 72 hours by trypan blue exclusion using a hemocytometer. After 1 week, colonies are stained with 1.25% crystal violet and quantified by measuring the absorbance at 595 nm. (Only for Reference)