关键词: LPS stimulation bone marrow derived macrophages metabolomics pro- and anti-inflammatory cytokines propolis

来  源:   DOI:10.3390/metabo10100413   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Previous research has shown that propolis has immunomodulatory activity. Extracts from two UK propolis samples were assessed for their anti-inflammatory activities by investigating their ability to alter the production of the cytokines: tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 from mouse bone marrow-derived macrophages co-stimulated with lipopolysaccharide (LPS). The propolis extracts suppressed the secretion of IL-1β and IL-6 with less effect on TNFα. In addition, propolis reduced the levels of nitric oxide formed by LPS-stimulated macrophages. Metabolomic profiling was carried out by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS increased the levels of intermediates involved in nitric oxide biosynthesis; propolis lowered many of these. In addition, LPS produced an increase in itaconate and citrate, and propolis treatment increased itaconate still further while greatly reducing citrate levels. Moreover, LPS treatment increased levels of glutathione (GSH) and intermediates in its biosynthesis, while propolis treatment boosted these still further. In addition, propolis treatment greatly increased levels of uridine diphosphate (UDP)-sugar conjugates. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by the inhibition of pro-inflammatory cytokines and by the metabolic reprogramming of LPS activity in macrophages.
摘要:
先前的研究表明蜂胶具有免疫调节活性。通过研究其改变细胞因子产生的能力来评估来自两个英国蜂胶样品的提取物的抗炎活性:肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β),来自小鼠骨髓来源的巨噬细胞的IL-6和IL-10与脂多糖(LPS)共刺激。蜂胶提取物抑制IL-1β和IL-6的分泌,对TNFα的影响较小。此外,蜂胶降低了LPS刺激的巨噬细胞形成的一氧化氮水平。在ZIC-pHILIC柱上通过液相色谱(LC)与质谱(MS)联用进行代谢组学分析。LPS增加了参与一氧化氮生物合成的中间体的水平;蜂胶降低了其中的许多。此外,LPS增加了衣康酸酯和柠檬酸盐,和蜂胶处理进一步增加了衣康酸,同时大大降低了柠檬酸盐水平。此外,LPS处理增加了谷胱甘肽(GSH)和中间体在其生物合成的水平,而蜂胶治疗进一步促进了这些。此外,蜂胶处理大大提高了尿苷二磷酸(UDP)-糖缀合物的水平。总的来说,结果表明,蜂胶提取物通过抑制促炎细胞因子和巨噬细胞中LPS活性的代谢重编程发挥抗炎作用。
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