Kwon Hyang-Mi, Choi Yean-Jung, Jeong Yu-Jin, Kang Sang-Wook, Kang Il-Jun, Lim Soon Sung, Kang Young-Hee
Department of Food and Nutrition and Silver Biotechnology Research Center, Hallym University, Chuncheon, Republic of Korea.
J Agric Food Chem. 2005 Jun 29;53(13):5150-7. doi: 10.1021/jf047854d.
Endothelial expression of cell adhesion molecules (CAM) including VCAM-1, E-selectin, and PECAM-1 plays a leading role in atherosclerosis. Phenolic flavones have been shown to have an anti-inflammatory property. This study examines whether 3',4'-dimethoxy-7-hydroxyflavone (methoxyflavone) and 2',3',7-trihydroxyflavone (hydroxyflavone) inhibited monocyte adhesion to TNF-alpha-activated endothelium via reduction of CAM expression in human umbilical vein endothelial cells (HUVEC). In stimulated HUVEC the expression of VCAM-1 and E-selectin was enhanced with increasing mRNA levels. Methoxyflavone markedly interfered with the THP-1 monocyte adhesion to TNF-alpha-stimulated HUVEC. At concentrations of > or =25 microM, methoxyflavone blocked the induction of VCAM-1 but not that of E-selectin on the activated HUVEC. Immunocytochemical staining showed that methoxyflavone modestly inhibited PECAM-1 expression induced by TNF-alpha. In contrast, hydroxyflavone minimally inhibited TNF-alpha-stimulated E-selectin expression without affecting VCAM-1 level. The inhibitory effect of methoxyflavone on THP-1 adhesion to HUVEC appears to be greater than that of hydroxyflavone, most likely due to a greater inhibition of CAM expression. Thus, some flavone derivatives containing methoxy groups may have therapeutic potential attenuating inflammatory response-related atherosclerosis.
包括血管细胞黏附分子-1（VCAM-1）、E-选择素和血小板内皮细胞黏附分子-1（PECAM-1）在内的细胞黏附分子（CAM）的内皮表达在动脉粥样硬化中起主导作用。酚类黄酮已被证明具有抗炎特性。本研究探讨3'，4'-二甲氧基-7-羟基黄酮（甲氧基黄酮）和2'，3'，7-三羟基黄酮（羟基黄酮）是否通过降低人脐静脉内皮细胞（HUVEC）中CAM的表达来抑制单核细胞黏附于肿瘤坏死因子-α（TNF-α）激活的内皮细胞。在受刺激的HUVEC中，VCAM-1和E-选择素的表达随着mRNA水平的升高而增强。甲氧基黄酮显著干扰THP-1单核细胞黏附于TNF-α刺激的HUVEC。在浓度≥25μM时，甲氧基黄酮可阻断激活的HUVEC上VCAM-1的诱导，但不阻断E-选择素的诱导。免疫细胞化学染色显示，甲氧基黄酮适度抑制TNF-α诱导的PECAM-1表达。相比之下，羟基黄酮对TNF-α刺激的E-选择素表达的抑制作用最小，且不影响VCAM-1水平。甲氧基黄酮对THP-1黏附于HUVEC的抑制作用似乎大于羟基黄酮，这很可能是由于对CAM表达的抑制作用更强。因此，一些含甲氧基的黄酮衍生物可能具有减轻炎症反应相关动脉粥样硬化的治疗潜力。
