Vieira Sara F, Gonçalves Samuel M, Gonçalves Virgínia M F, Tiritan Maria E, Cunha Cristina, Carvalho Agostinho, Reis Rui L, Ferreira Helena, Neves Nuno M
3B's Research Group, I3BS - Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Planta Med. 2024 Dec;90(15):1143-1155. doi: 10.1055/a-2436-9664. Epub 2024 Oct 17.
has been traditionally used to strengthen the immune system. Therefore, herein, we investigated the potential of aqueous extracts (AEs) obtained from flowers (F), leaves (L), or roots (R) as an immune booster in human primary monocyte-derived macrophages (hMDMs). Additionally, to identify the main class of compounds (phenolic/carboxylic acids vs. alkylamides) responsible for the bioactivity, the three AEs were fractioned by semi-preparative high-performance liquid chromatography (HPLC). The AEs and the isolated phenolic/carboxylic acidic fractions were not cytotoxic for hMDMs for all tested concentrations, as confirmed by the metabolic activity and DNA content assays. Moreover, AE drastically induced the production of the interleukin (IL)-6 and tumor necrosis factor (TNF)-, with a minimal effect on IL-1 and prostaglandin E2 (PGE2), supporting their potential for macrophage activation. Interestingly, in the presence of the phenolic/carboxylic acidic fractions, this efficacy considerably decreased, suggesting a complementary effect between compounds. AE also triggered the phosphorylation of the extracellular signal-regulated kinase (ERK) 1/2 and p38 signaling pathways and upregulated the cyclooxygenase (COX)-2 expression in hMDMs. Overall, AE-F was demonstrated to be the most powerful immunostimulant extract that can be related to their higher number in identified bioactive compounds compared to AE-L and AE-R. These results highlight the efficiency of AE to enhance the function of a key cell type of the immune system and their potential as immunostimulant formulations for patients with a compromised immune system due to certain diseases (e.g., acquired immunodeficiencies) and treatments (e.g., chemotherapy).
传统上一直被用于增强免疫系统。因此，在此我们研究了从花（F）、叶（L）或根（R）中获得的水提取物（AE）作为人类原代单核细胞衍生巨噬细胞（hMDM）免疫增强剂的潜力。此外，为了确定负责生物活性的主要化合物类别（酚类/羧酸类与烷基酰胺类），通过半制备高效液相色谱（HPLC）对三种AE进行了分离。代谢活性和DNA含量测定证实，对于所有测试浓度，AE和分离出的酚类/羧酸酸性组分对hMDM均无细胞毒性。此外，AE显著诱导白细胞介素（IL）-6和肿瘤坏死因子（TNF）-的产生，对IL-1和前列腺素E2（PGE2）的影响最小，这支持了它们激活巨噬细胞的潜力。有趣的是，在存在酚类/羧酸酸性组分的情况下，这种功效显著降低，表明化合物之间存在互补作用。AE还触发了细胞外信号调节激酶（ERK）1/2和p38信号通路的磷酸化，并上调了hMDM中环氧合酶（COX）-2的表达。总体而言，AE-F被证明是最强大的免疫刺激提取物，这可能与其鉴定出的生物活性化合物数量比AE-L和AE-R更多有关。这些结果突出了AE增强免疫系统关键细胞类型功能的效率，以及它们作为免疫刺激制剂对于因某些疾病（如获得性免疫缺陷）和治疗（如化疗）导致免疫系统受损患者的潜力。
