Department of Food and Nutrition , Hallym University , Chuncheon 200-702 , Korea.
Department of Bio-Food Science & Technology , Far East University , Eumseong , Korea.
J Agric Food Chem. 2018 Jul 25;66(29):7643-7654. doi: 10.1021/acs.jafc.8b01808. Epub 2018 Jul 11.
Airway inflammation has been implicated in evoking progressive pulmonary disorders including chronic obstructive pulmonary disease (COPD) and asthma as a result of exposure to inhaled irritants, characterized by airway fibrosis, mucus hypersecretion, and loss of alveolar integrity. The current study examined whether oleuropein, a phenylethanoid found in olive leaves, inhibited pulmonary inflammation in experimental models of interleukin (IL)-4-exposed bronchial BEAS-2B epithelial cells and ovalbumin (OVA)- or cigarette smoke (CS)-exposed BALB/c mice. Nontoxic oleuropein at 1-20 μM diminished eotaxin-1-mediated induction of α-smooth muscle actin and mucin 5AC in epithelial cells stimulated by IL-4 at the transcriptional levels. Oral supplementation of 10-20 mg/kg oleuropein reduced the airway influx of eosinophils and lymphocytes as well as IL-4 secretion in lung promoted by OVA inhalation or CS. In addition, oleuropein suppressed infiltration of macrophages and neutrophils through blocking OVA inhalation- and CS-promoted induction of ICAM-1, F4/80, CD68, and CD11b in airways. OVA-exposed pulmonary fibrosis was detected, while alveolar emphysema was evident in CS-exposed mouse lungs. In alveolar epithelial A549 cells exposed to CS extracts, oleuropein attenuated apoptotic cell loss. Collectively, oleuropein inhibited pulmonary inflammation leading to asthmatic fibrosis and alveolar emphysema driven by influx of inflammatory cells in airways exposed OVA or CS. Therefore, oleuropein may be a promising anti-inflammatory agent for treating asthma and COPD.
气道炎症与吸入性刺激物引起的慢性阻塞性肺疾病 (COPD) 和哮喘等进行性肺部疾病有关，其特征为气道纤维化、黏液过度分泌和肺泡完整性丧失。本研究旨在探讨橄榄叶中苯乙醇苷类化合物橄榄苦苷是否能抑制白细胞介素 (IL)-4 暴露的支气管 BEAS-2B 上皮细胞和卵清蛋白 (OVA) 或香烟烟雾 (CS) 暴露的 BALB/c 小鼠的肺部炎症。在转录水平上，无毒浓度为 1-20μM 的橄榄苦苷可减弱 IL-4 刺激的上皮细胞中嗜酸性粒细胞趋化因子-1 介导的α-平滑肌肌动蛋白和黏蛋白 5AC 的诱导。口服补充 10-20mg/kg 橄榄苦苷可减少 OVA 吸入或 CS 促进的气道内嗜酸性粒细胞和淋巴细胞以及 IL-4 分泌。此外，橄榄苦苷通过阻断 OVA 吸入和 CS 促进的气道中细胞间黏附分子-1、F4/80、CD68 和 CD11b 的诱导，抑制巨噬细胞和中性粒细胞的浸润。在 OVA 暴露的肺纤维化模型中检测到肺泡肺气肿，而在 CS 暴露的小鼠肺部则表现为明显的肺泡肺气肿。在 CS 提取物暴露的肺泡上皮 A549 细胞中，橄榄苦苷可减轻细胞凋亡。综上所述，橄榄苦苷可抑制气道炎症，从而抑制由 OVA 或 CS 诱导的炎症细胞流入导致的哮喘性纤维化和肺泡肺气肿。因此，橄榄苦苷可能是治疗哮喘和 COPD 的一种有前途的抗炎药物。
