González de Llano Dolores, Roldán Mikel, Parro Laura, Bartolomé Begoña, Moreno-Arribas M Victoria
Department of Food Biotechnology and Microbiology, Institute of Food Science Research, CIAL (CSIC-UAM), C/Nicolás Cabrera 9, 28049 Madrid, Spain.
Metabolites. 2023 Jan 9;13(1):108. doi: 10.3390/metabo13010108.
The aim of this study was to investigate whether microbial-derived phenolic acids, 3,4-dihydroxyphenylacetic (DHPA), protocatechuic acid (PCA), and dihydrocaffeic acid (DHCFA) and their conjugated forms (DHCFA 3-O-sulfate and DHCFA 3-O-β-D-glucuronide), exhibit protective effects against neuroinflammation and oxidative stress. Experiments were performed on human neuronal SH-SY5Y cells stimulated with bacterial lipopolysaccharide (LPS) and -butyl hydroperoxide (BHP). Anti-inflammatory activity in terms of pro-inflammatory cytokine production was also evaluated in LPS-stimulated RAW 264.7 macrophages as a reactive microglial model. Treatment of the SH-SY5Y cells with the free phenolic acids, as well as with the conjugated metabolites, at physiologically concentrations (1, 10 and 50 μM), resulted in increased cell viability of LPS- and BHP-stimulated cells. Phenolic metabolites and, especially, the conjugated derivatives also protected neuronal cells through significant attenuation of inflammation by decreasing ROS levels. Furthermore, the conjugated and microbial-derived phenolic metabolites significantly inhibited the secretion of proinflammatory cytokines (TNF-α, IL-6, and IL-8) in LPS-stimulated macrophages. Among the phenolic metabolites tested, different efficacies were observed, with the glucuronide form standing out. Overall, these results suggest, for the first time, that conjugated derivatives of phenolic acids seem to be more effective at protecting neurons from inflammation damage and oxidative stress. Further in vivo studies are warranted.
本研究的目的是调查微生物衍生的酚酸、3,4-二羟基苯乙酸（DHPA）、原儿茶酸（PCA）和二氢咖啡酸（DHCFA）及其共轭形式（DHCFA 3-O-硫酸盐和DHCFA 3-O-β-D-葡萄糖醛酸苷）是否对神经炎症和氧化应激具有保护作用。实验在用人脂多糖（LPS）和叔丁基过氧化氢（BHP）刺激的人神经元SH-SY5Y细胞上进行。还在LPS刺激的RAW 264.7巨噬细胞作为反应性小胶质细胞模型中评估了促炎细胞因子产生方面的抗炎活性。用生理浓度（1、10和50μM）的游离酚酸以及共轭代谢物处理SH-SY5Y细胞，导致LPS和BHP刺激细胞的细胞活力增加。酚类代谢物，尤其是共轭衍生物，还通过降低ROS水平显著减轻炎症，从而保护神经元细胞。此外，共轭和微生物衍生的酚类代谢物显著抑制LPS刺激的巨噬细胞中促炎细胞因子（TNF-α、IL-6和IL-8）的分泌。在所测试的酚类代谢物中，观察到不同的功效，其中葡萄糖醛酸苷形式最为突出。总体而言，这些结果首次表明，酚酸的共轭衍生物似乎在保护神经元免受炎症损伤和氧化应激方面更有效。有必要进行进一步的体内研究。
