Winterbone Mark S, Tribolo Sandra, Needs Paul W, Kroon Paul A, Hughes David A
Phytochemicals and Health Programme, Institute of Food Research, Norwich Research Park, Norwich, Norfolk, NR4 7UA, UK.
Atherosclerosis. 2009 Feb;202(2):431-8. doi: 10.1016/j.atherosclerosis.2008.04.040. Epub 2008 May 1.
Dietary flavonoids have been shown to have a number of anti-inflammatory properties, including decreasing the expression of adhesion molecules. Flavonoids however, are metabolised during absorption and the forms reaching the systemic circulation are glucuronidated, sulfated and methylated. Most previous studies of the effects of flavonoids have used the parent compounds rather than the metabolites found in blood plasma and we have recently shown that metabolites of quercetin can retain some of the anti-inflammatory properties of the parent aglycone when used to treat human umbilical endothelial cells (HUVEC). Using both physiologically achievable (2 microM) and supraphysiological (10 microM) concentrations, we investigated the ability of quercetin and its predominant human metabolites to attenuate the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) in human umbilical artery smooth muscle cells (HUASMC) activated by tumor necrosis factor-alpha (TNFalpha). Quercetin was able to reduce TNFalpha-induced upregulation of VCAM-1, ICAM-1 and MCP-1 at both the protein and transcript (mRNA) level in HUASMC. However the quercetin metabolites, quercetin 3'-sulfate, quercetin 3-glucuronide and 3'-methylquercetin 3-glucuronide, had no effect on TNFalpha-induced up regulation of adhesion molecule or chemokine expression, at either concentration tested. These data do not support the notion that the vascular anti-inflammatory effects of quercetin consumption are mediated through effects on smooth muscle cells.
膳食类黄酮已被证明具有多种抗炎特性，包括降低黏附分子的表达。然而，类黄酮在吸收过程中会被代谢，进入体循环的形式是葡萄糖醛酸化、硫酸化和甲基化的。此前大多数关于类黄酮作用的研究都使用母体化合物，而非血浆中发现的代谢产物。最近我们发现，槲皮素的代谢产物在用于处理人脐静脉内皮细胞（HUVEC）时，可保留母体苷元的一些抗炎特性。我们使用生理可达到的浓度（2 microM）和超生理浓度（10 microM），研究了槲皮素及其主要人体代谢产物在肿瘤坏死因子-α（TNFα）激活的人脐动脉平滑肌细胞（HUASMC）中减弱血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）和单核细胞趋化蛋白-1（MCP-1）表达的能力。槲皮素能够在蛋白质和转录本（mRNA）水平上降低HUASMC中TNFα诱导的VCAM-1、ICAM-1和MCP-1上调。然而，在测试的两种浓度下，槲皮素代谢产物槲皮素3'-硫酸盐、槲皮素3-葡萄糖醛酸苷和3'-甲基槲皮素3-葡萄糖醛酸苷对TNFα诱导的黏附分子或趋化因子表达上调均无影响。这些数据不支持食用槲皮素的血管抗炎作用是通过对平滑肌细胞的作用介导的这一观点。
