Laboratoire de Biochimie Analytique et de Biotechnologie, Faculté des Sciences Biologiques et des Sciences Agronomiques, Université Mouloud Mammeri de Tizi-Ouzou, Tizi Ouzou, Algeria.
INSERM U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation (CRI), Laboratoire d'Excellence Inflamex, Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, 16 Rue Henri Huchard, Paris, France.
Inflammopharmacology. 2017 Dec;25(6):673-680. doi: 10.1007/s10787-017-0367-7. Epub 2017 Jul 15.
Oleuropein and hydroxytyrosol are polyphenols that are extracted from olives and are major biological active components of olives and olive oil. Oleuropein and hydroxytyrosol exhibit interesting pharmacological effects on cells, and have been shown to have many health benefits such as anti-inflammatory effects. These effects were mainly attributed to their ability to scavenge the reactive oxygen species (ROS) produced by phagocytes such as neutrophils. The aim of this study was to investigate the effect of oleuropein and hydroxytyrosol on other neutrophil functions.
Human neutrophils were isolated from healthy donors. ROS production was measured by luminol-amplified chemiluminescence. Degranulation was assessed by measuring myeloperoxidase activity and Western blots. Chemotaxis was assessed by the under-agarose chemotaxis assay. Phosphorylated proteins were assessed by gel electrophoresis and Western blots.
We show that in addition to their ROS scavenging effect, oleuropein and hydroxytyrosol significantly inhibited the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF)-induced degranulation of azurophilic and specific granules as measured by myeloperoxidase and lactoferrin release, respectively. We also show that oleuropein and hydroxytyrosol reduced fMLF-induced neutrophil chemotaxis. Interestingly, both agents impaired the fMLF-induced AKT, p38MAPKinase, and ERK1/2 phosphorylation, signaling molecules that are involved in pathways regulating neutrophil functions.
Our data suggest that the anti-inflammatory properties of oleuropein and hydroxytyrosol are not only restricted to their ROS scavenging effect, but also involve the inhibition of two other major pro-inflammatory neutrophil functions.
橄榄苦苷和羟基酪醇是从橄榄中提取的多酚，是橄榄和橄榄油的主要生物活性成分。橄榄苦苷和羟基酪醇对细胞表现出有趣的药理作用，并且已显示出许多健康益处，如抗炎作用。这些作用主要归因于它们清除吞噬细胞（如中性粒细胞）产生的活性氧（ROS）的能力。本研究旨在研究橄榄苦苷和羟基酪醇对其他中性粒细胞功能的影响。
从健康供体中分离人中性粒细胞。通过发光氨增强化学发光法测量 ROS 产生。通过测量髓过氧化物酶活性和 Western blot 评估脱粒。通过琼脂下趋化性测定评估趋化性。通过凝胶电泳和 Western blot 评估磷酸化蛋白。
我们表明，除了其清除 ROS 的作用外，橄榄苦苷和羟基酪醇还显著抑制了细菌肽 N-甲酰基-甲硫氨酸-亮氨酸-苯丙氨酸（fMLF）诱导的嗜中性粒细胞的脱粒，这通过髓过氧化物酶和乳铁蛋白释放来衡量。我们还表明，橄榄苦苷和羟基酪醇减少了 fMLF 诱导的中性粒细胞趋化性。有趣的是，两种药物均损害了 fMLF 诱导的 AKT、p38MAPK 和 ERK1/2 磷酸化，这些信号分子参与调节中性粒细胞功能的途径。
我们的数据表明，橄榄苦苷和羟基酪醇的抗炎特性不仅限于其清除 ROS 的作用，还涉及抑制另外两种主要的促炎中性粒细胞功能。
