Institute of Pharmacology and Toxicology, Rostock University Medical Center, Schillingallee 70, 18057 Rostock, Germany.
Int J Mol Sci. 2023 Nov 7;24(22):16047. doi: 10.3390/ijms242216047.
The monocyte chemoattractant protein-1 (MCP-1), also known as chemokine (CC motif) ligand 2 (CCL2), is involved in the formation, progression, and destabilization of atheromatous plaques. Flavonoids, found in fruits and vegetables, have been associated with various health-promoting properties, including antioxidant, anti-inflammatory, and cardioprotective effects. In the present study, the flavonoids quercetin, kaempferol, and luteolin, but not cannflavin A, were shown to substantially inhibit interleukin (IL)-1β-induced MCP-1 mRNA and protein expression in human coronary artery endothelial cells (HCAEC). At the functional level, conditioned medium (CM) from IL-1β-stimulated HCAEC caused an increase in the migration of THP-1 monocytes compared with CM from unstimulated HCAEC. However, this induction was suppressed when IL-1β-treated HCAEC were coincubated with quercetin, kaempferol, or luteolin. The functional importance of MCP-1 in IL-1β-induced monocyte migration was supported by experiments showing that neutralization of MCP-1 in the CM of IL-1β-treated HCAEC led to a significant inhibition of migration. In addition, a concentration-dependent induction of monocyte migration in the presence of recombinant MCP-1 was demonstrated. Collectively, the flavonoids quercetin, kaempferol, and luteolin were found to exert potential antiatherogenic effects in HCAEC, challenging further studies with these compounds.
单核细胞趋化蛋白-1（MCP-1），也称为趋化因子（CC 基序）配体 2（CCL2），参与动脉粥样硬化斑块的形成、进展和不稳定。类黄酮存在于水果和蔬菜中，与各种促进健康的特性有关，包括抗氧化、抗炎和心脏保护作用。在本研究中，类黄酮槲皮素、山奈酚和木樨草素，但不是大麻素 A，被证明可显著抑制人冠状动脉内皮细胞（HCAEC）中白细胞介素（IL）-1β诱导的 MCP-1 mRNA 和蛋白表达。在功能水平上，与未刺激的 HCAEC 的 CM 相比，来自 IL-1β 刺激的 HCAEC 的条件培养基（CM）引起 THP-1 单核细胞迁移增加。然而，当用槲皮素、山奈酚或木樨草素共孵育时，IL-1β 处理的 HCAEC 会抑制这种诱导。在 IL-1β 诱导的单核细胞迁移中 MCP-1 的功能重要性得到了实验的支持，这些实验表明，中和 IL-1β 处理的 HCAEC 的 CM 中的 MCP-1 导致迁移显著抑制。此外，还证明了在存在重组 MCP-1 的情况下，单核细胞迁移呈浓度依赖性诱导。总之，发现类黄酮槲皮素、山奈酚和木樨草素在 HCAEC 中具有潜在的抗动脉粥样硬化作用，这为进一步研究这些化合物提供了挑战。
