Jia Zhenquan, Babu Pon Velayutham Anandh, Si Hongwei, Nallasamy Palanisamy, Zhu Hong, Zhen Wei, Misra Hara P, Li Yunbo, Liu Dongmin
Department of Biology, University of North Carolina at Greensboro, Greensboro, 27412, USA.
Int J Cardiol. 2013 Oct 3;168(3):2637-45. doi: 10.1016/j.ijcard.2013.03.035. Epub 2013 Apr 12.
Genistein, a soy isoflavone, has received wide attention for its potential to improve vascular function, but the mechanism of this effect is unclear. Here, we report that genistein at physiological concentrations (0.1 μM-5 μM) significantly inhibited TNF-α-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis. Genistein also significantly suppressed TNF-α-induced production of adhesion molecules and chemokines such as sICAM-1, sVCAM-1, sE-Selectin, MCP-1 and IL-8, which play key role in the firm adhesion of monocytes to activated endothelial cells (ECs). Genistein at physiologically relevant concentrations didn't significantly induce antioxidant enzyme activities or scavenge free radicals. Further, blocking the estrogen receptors (ERs) in ECs didn't alter the preventive effect of genistein on endothelial inflammation. However, inhibition of protein kinase A (PKA) significantly attenuated the inhibitory effects of genistein on TNF-α-induced monocyte adhesion to ECs as well as the production of MCP-1 and IL-8. In animal study, dietary genistein significantly suppressed TNF-α-induced increase in circulating chemokines and adhesion molecules in C57BL/6 mice. Genistein treatment also reduced VCAM-1 and monocytes-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion, genistein protects against TNF-α-induced vascular endothelial inflammation both in vitro and in vivo models. This anti-inflammatory effect of genistein is independent of the ER-mediated signaling machinery or antioxidant activity, but mediated via the PKA signaling pathway.
染料木黄酮是一种大豆异黄酮，因其改善血管功能的潜力而受到广泛关注，但其作用机制尚不清楚。在此，我们报告生理浓度（0.1 μM - 5 μM）的染料木黄酮可显著抑制肿瘤坏死因子-α（TNF-α）诱导的单核细胞与人脐静脉内皮细胞的黏附，这是动脉粥样硬化发病机制中的关键事件。染料木黄酮还显著抑制TNF-α诱导的黏附分子和趋化因子的产生，如可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）、可溶性E-选择素、单核细胞趋化蛋白-1（MCP-1）和白细胞介素-8（IL-8），这些在单核细胞与活化内皮细胞（ECs）的牢固黏附中起关键作用。生理相关浓度的染料木黄酮不会显著诱导抗氧化酶活性或清除自由基。此外，阻断内皮细胞中的雌激素受体（ERs）并不会改变染料木黄酮对内皮炎症的预防作用。然而，抑制蛋白激酶A（PKA）可显著减弱染料木黄酮对TNF-α诱导的单核细胞与内皮细胞黏附以及MCP-1和IL-8产生的抑制作用。在动物研究中，饮食中的染料木黄酮可显著抑制TNF-α诱导的C57BL/6小鼠循环趋化因子和黏附分子的增加。染料木黄酮治疗还可减少TNF-α处理小鼠主动脉中的VCAM-1和单核细胞来源的F4/8阳性巨噬细胞。总之，染料木黄酮在体外和体内模型中均可预防TNF-α诱导的血管内皮炎症。染料木黄酮的这种抗炎作用独立于ER介导的信号机制或抗氧化活性，而是通过PKA信号通路介导的。
