Department of Human Sciences, Tennessee State University, Nashville, Tennessee, USA; Department of Veterinary Medicine, Northwest University for Nationalities, Lanzhou, Gansu China.
Department of Human Sciences, Tennessee State University, Nashville, Tennessee, USA; Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
J Nutr Biochem. 2022 Oct;108:109083. doi: 10.1016/j.jnutbio.2022.109083. Epub 2022 Jun 10.
Chronic increased pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) play critical roles in the development of endothelial dysfunction and therefore induce cardiovascular disease. Although phytochemicals have the potential ability to reduce the risk of CVD, the big gap between required high concentration in cells and the low bioavailability in the blood of phytochemicals compromise their therapeutic potentials. This study aims to investigate if combined phytochemicals at low levels exert a synergistic anti-inflammatory effect and to define relevant molecular mechanisms. Our results found that combined curcumin (5 µM) and resveratrol (5 µM) synergistically (combination index is 0.78) inhibited TNF-α-induced monocytes adhesion to human endothelial EA.hy 926 cells while the individual chemicals did not have such effect at the selected concentrations. The concentrations of curcumin (5 µM) and resveratrol (5 µM) are very close to the maximum level of curcumin (3.56 µM) and resveratrol (2 µM) in human blood. Dietary supplementation of combined curcumin (500mg/kg) and resveratrol (200mg/kg) synergistically reduced TNF-α-induced vascular inflammation in C57BL/6 mice with a similar pattern in cells. Moreover, the combination ameliorated the TNF-α-induced protein expressions and circulating levels of vascular cell adhesion molecule 1 and monocyte chemotactic protein-1 in EA.hy 926 cells, mice aorta and serum. Furthermore, combined curcumin and resveratrol significantly inhibited TNF-α-induced nuclear factor-kappaB (NF-κB) p65 nuclear protein expression than that by the individual chemical alone in EA.hy 926 cells, indicating that the synergistic effect of the combination may result from that curcumin reduces the required minimum concentration for resveratrol to inhibit the nuclear translocation of NF-κB. In conclusion, the combination of curcumin and resveratrol protects against TNF-α-induced vascular inflammation by suppressing NF-κB signaling in vitro and in vivo models. This study suggests that dietary intake of a combination of curcumin and resveratrol or its foods may be a practical, safe approach to prevent vascular inflammation and therefore prevent/treat vascular diseases in humans.
慢性增加的促炎细胞因子，如肿瘤坏死因子-α（TNF-α），在血管内皮功能障碍的发展中起着关键作用，因此导致心血管疾病。尽管植物化学物质具有降低 CVD 风险的潜力，但植物化学物质在细胞中所需的高浓度与血液中低生物利用度之间存在巨大差距，这限制了它们的治疗潜力。本研究旨在探讨低水平的组合植物化学物质是否具有协同抗炎作用，并确定相关的分子机制。我们的研究结果发现，联合姜黄素（5µM）和白藜芦醇（5µM）协同（组合指数为 0.78）抑制 TNF-α诱导的单核细胞黏附到人类内皮 EA.hy926 细胞，而在所选浓度下，单独的化学物质没有这种作用。姜黄素（5µM）和白藜芦醇（5µM）的浓度非常接近人类血液中姜黄素（3.56µM）和白藜芦醇（2µM）的最高水平。联合姜黄素（500mg/kg）和白藜芦醇（200mg/kg）的饮食补充协同降低 C57BL/6 小鼠 TNF-α诱导的血管炎症，细胞中也存在类似的模式。此外，该组合改善了 TNF-α诱导的 EA.hy926 细胞、小鼠主动脉和血清中血管细胞黏附分子 1 和单核细胞趋化蛋白-1 的蛋白表达和循环水平。此外，联合姜黄素和白藜芦醇显著抑制 TNF-α诱导的核因子-κB（NF-κB）p65 核蛋白表达，优于单独使用化学物质，表明组合的协同作用可能是由于姜黄素降低了白藜芦醇抑制 NF-κB 核转位所需的最低浓度。总之，姜黄素和白藜芦醇的组合通过抑制体外和体内模型中 NF-κB 信号通路来保护血管免受 TNF-α诱导的血管炎症。这项研究表明，饮食摄入姜黄素和白藜芦醇的组合或其食物可能是一种实用且安全的方法，可预防血管炎症，从而预防/治疗人类血管疾病。
