Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Food Funct. 2024 Jan 2;15(1):172-182. doi: 10.1039/d3fo04026g.
Our laboratory has established a comprehensive program to investigate the phytochemical composition and nutritional/medicinal properties of phenolic-enriched maple syrup extract (MSX). Previous studies support MSX's therapeutic potential in diverse disease models, primarily through its anti-inflammatory effects. We recently demonstrated MSX's ability to regulate inflammatory signaling pathways and modulate inflammatory markers and proteins in a lipopolysaccharide (LPS)-induced peritonitis mouse model. However, MSX's immunoregulatory properties remain unknown. Herein, we investigated MSX's immunoregulatory properties for the first time using an integrated approach, combining data-dependent acquisition (DDA) and data-independent acquisition (DIA) strategies in a proteomic analysis of spleen tissue collected from the aforementioned peritonitis mouse model. Additionally, we conducted immune cell activation assays using macrophages and T lymphocytes. The DIA analysis unveiled a distinctive expression pattern involving three proteins-Krt83, Thoc2, and Vps16-which were present in both the control and MSX-treated groups but absent in the LPS-induced model group. Furthermore, proteins Ppih and Dpp9 exhibited significant reductions in the MSX-treated group. Ingenuity pathway analysis indicated that MSX may modulate several critical signaling pathways, exerting a suppressive effect on immune responses in various cell types involved in both innate and adaptive immunity. Our cell assays supported findings from the proteomics, revealing that MSX significantly reduced the levels of interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in LPS-stimulated human macrophage cells, as well as the levels of IL-2 in anti-CD3/anti-CD28-induced Jurkat T cells. Taken together, our investigations provide evidence that MSX exerts immune regulatory effects that impact both innate and adaptive immunity, which adds to the data supporting MSX's development as a functional food.
我们的实验室已经建立了一个综合项目，旨在研究富含酚类的枫糖浆提取物（MSX）的植物化学成分和营养/药用特性。先前的研究支持 MSX 在多种疾病模型中的治疗潜力，主要是通过其抗炎作用。我们最近证明了 MSX 能够调节炎症信号通路，并在脂多糖（LPS）诱导的腹膜炎小鼠模型中调节炎症标志物和蛋白质。然而，MSX 的免疫调节特性尚不清楚。在此，我们首次使用一种综合方法研究了 MSX 的免疫调节特性，该方法结合了数据依赖采集（DDA）和数据独立采集（DIA）策略，对来自上述腹膜炎小鼠模型的脾脏组织进行了蛋白质组学分析。此外，我们使用巨噬细胞和 T 淋巴细胞进行了免疫细胞激活测定。DIA 分析揭示了一种独特的表达模式，涉及三种蛋白质-Krt83、Thoc2 和 Vps16-它们存在于对照组和 MSX 处理组中，但不存在于 LPS 诱导组中。此外，Ppih 和 Dpp9 蛋白在 MSX 处理组中显著减少。Ingenuity 途径分析表明，MSX 可能调节几个关键信号通路，对先天和适应性免疫中涉及的各种细胞类型的免疫反应发挥抑制作用。我们的细胞测定支持蛋白质组学的发现，表明 MSX 可显著降低 LPS 刺激的人巨噬细胞中白细胞介素 1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的水平，以及抗-CD3/抗-CD28 诱导的 Jurkat T 细胞中 IL-2 的水平。总之，我们的研究提供了证据表明 MSX 发挥免疫调节作用，影响先天和适应性免疫，这为支持 MSX 作为功能性食品的开发提供了更多数据。
