Department of Food, Environmental and Nutritional Sciences (DeFENS), Università Degli Studi Di Milano, 20133, Milan, Italy.
Department of Public Health, Section of Environmental Health, University of Copenhagen, 1014, Copenhagen K, Denmark.
Eur J Nutr. 2022 Mar;61(2):1003-1014. doi: 10.1007/s00394-021-02714-w. Epub 2021 Oct 26.
Chlorogenic acid (CGA) and caffeic acid (CA) are bioactive compounds in whole grains, berries, apples, some citrus fruits and coffee, which are hypothesized to promote health-beneficial effects on the cardiovascular system. This study aimed to evaluate the capacity of CGA and CA to reduce lipid accumulation in macrophages, recognized as a critical stage in the progression of atherosclerosis. Furtherly, the modulation of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor- γ1 (PPAR-γ1), as transcription factors involved in lipid metabolism, was evaluated.
THP-1-derived macrophages were treated for 24 h with 0.03, 0.3, 3 and 30 μM of CGA and CA, tested alone or in combination, and a solution of oleic/palmitic acid (500 μM, 2:1 ratio). Lipid storage was assessed spectrophotometrically through fluorescent staining of cells with Nile red. C/EBPβ and PPAR-γ1 mRNA and protein levels were evaluated by RT-PCR and enzyme-linked immunosorbent assay, respectively.
The mix of CGA + CA (1:1 ratio) reduced lipid accumulation at all concentrations tested, except for the highest one. The greatest effect ( - 65%; p < 0.01) was observed at the concentration of 0.3 μM for each compound. The same concentration significantly (p < 0.01) downregulated C/EBPβ and PPAR-γ1 gene expression and reduced their protein levels at 2 h and 24 h, respectively.
The results indicate that the capacity of CGA + CA mix to reduce lipid storage in macrophages is mediated by a reduction in the expression of transcription factors C/EBPβ and PPAR-γ1.
绿原酸(CGA)和咖啡酸(CA)是全谷物、浆果、苹果、一些柑橘类水果和咖啡中的生物活性化合物,据推测它们对心血管系统有有益健康的作用。本研究旨在评估 CGA 和 CA 降低巨噬细胞中脂质积累的能力,巨噬细胞被认为是动脉粥样硬化进展的关键阶段。此外,还评估了参与脂质代谢的转录因子 CCAAT/增强子结合蛋白β(C/EBPβ)和过氧化物酶体增殖物激活受体-γ1(PPAR-γ1)的调节作用。
用 0.03、0.3、3 和 30μM 的 CGA 和 CA 单独或联合处理 THP-1 衍生的巨噬细胞 24 小时,并测试其对油酸/棕榈酸(500μM,2:1 比例)的反应。通过尼罗红荧光染色分光光度法评估细胞内脂质储存。通过 RT-PCR 和酶联免疫吸附试验分别评估 C/EBPβ 和 PPAR-γ1 mRNA 和蛋白水平。
CGA+CA(1:1 比例)混合物在所有测试浓度下均降低了脂质积累,除了最高浓度外。在每种化合物的 0.3μM 浓度下观察到最大效果(-65%;p<0.01)。相同浓度在 2 小时和 24 小时时分别显著(p<0.01)下调 C/EBPβ 和 PPAR-γ1 基因表达,并降低其蛋白水平。
结果表明,CGA+CA 混合物降低巨噬细胞中脂质储存的能力是通过降低转录因子 C/EBPβ 和 PPAR-γ1 的表达来介导的。