Department of Pharmacy, University of Salerno, Fisciano, SA, Italy.
PhD Program in Drug Discovery and Development, University of Salerno, Fisciano, SA, Italy.
Food Funct. 2021 Dec 13;12(24):12800-12811. doi: 10.1039/d1fo02361f.
Dendritic cells (DCs) represent a heterogeneous family of immune cells that link innate and adaptive immunity and their activation is linked to metabolic changes that are essential to support their activity and function. Hence, targeting the metabolism of DCs represents an opportunity to modify the inflammatory and immune response. Among the natural matrices, (Hop) compounds have recently been shown to exhibit immunomodulatory and anti-inflammatory activity. This study aimed to evaluate the ability of specific Hop fractions to modulate DCs metabolism after stimulation with lipopolysaccharide (LPS) by an untargeted metabolomics approach and compare their effect with flavonol quercetin. Following liquid chromatography-based fractionation, three fractions (A, B, and C) were obtained and tested. Cytokine and gene expression were evaluated using ELISA and qPCR, respectively, while the untargeted metabolomics analysis was performed using a combined HILIC-HRMS and DI-FT-ICR approach. The HOP C fraction and quercetin could both reduce the production of several inflammatory cytokines such as IL-6, IL-1α, IL-1β, and TNF, but differently from quercetin, the HOP C mechanism is independent of extracellular iron-sequestration and showed significant upregulation of the / pathway and compared to quercetin. The untargeted analysis revealed the modulation of several key pathways linked to pro-inflammatory and glycolytic phenotypes. In particular, HOP C treatment could modulate the oxidative step of the pentose phosphate pathway (PPP) and reduce the inflammatory mediator succinate, citrulline, and purine-pyrimidine metabolism, differently from quercetin. These results highlight the potential anti-inflammatory mechanism of specific Hop-derived compounds in restoring the dysregulated metabolism in DCs, which can be used in preventive or adjuvant therapies to suppress the undesirable inflammatory response.
树突状细胞 (DCs) 代表了一类具有异质性的免疫细胞，它们连接先天免疫和适应性免疫，其激活与代谢变化有关，这些变化对于支持其活性和功能至关重要。因此，针对 DCs 的代谢进行靶向治疗代表了一种改变炎症和免疫反应的机会。在天然基质中，(Hop) 化合物最近被证明具有免疫调节和抗炎活性。本研究旨在通过非靶向代谢组学方法评估特定 Hop 馏分在 LPS 刺激后调节 DCs 代谢的能力，并将其与类黄酮槲皮素进行比较。在基于液相色谱的分级后，获得了三个馏分 (A、B 和 C) 并进行了测试。细胞因子和基因表达分别通过 ELISA 和 qPCR 进行评估，而非靶向代谢组学分析则使用 HILIC-HRMS 和 DI-FT-ICR 联合方法进行。Hop C 馏分和槲皮素都可以减少几种炎症细胞因子的产生，如 IL-6、IL-1α、IL-1β 和 TNF，但与槲皮素不同的是，Hop C 的作用机制不依赖于细胞外铁螯合，与槲皮素相比，显著上调了 / 途径。非靶向分析显示，几种与促炎和糖酵解表型相关的关键途径发生了调节。特别是，Hop C 处理可以调节戊糖磷酸途径 (PPP) 的氧化步骤，并减少炎症介质琥珀酸、瓜氨酸和嘌呤嘧啶代谢，这与槲皮素不同。这些结果突出了特定 Hop 衍生化合物在恢复 DCs 失调代谢方面的潜在抗炎机制，可用于预防或辅助治疗以抑制不良炎症反应。
