a College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, BK21 Plus KNU Multi-Omics based Creative Drug Research Team, Kyungpook National University , Daegu , Republic of Korea.
b Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Daejeon , Republic of Korea.
J Toxicol Environ Health A. 2019;82(12):727-740. doi: 10.1080/15287394.2019.1646174. Epub 2019 Jul 25.
Particulate matter 2.5 (PM), with an aerodynamic diameter of ≤2.5 μm, is the primary air pollutant that plays a key role associated with lung injury produced by loss of vascular barrier integrity. Decne (Chinese yam), a perennial plant belonging to Dioscoreaceae family, is widely cultivated in tropical and subtropical regions across Asia. Both aerial parts and root of are consumed for nutritional and medicinal purposes. The aim of this study was to (1) identify the bioactive compounds present in peel which may be responsible for inhibition of PM-induced pulmonary inflammation in mice and (2) examine mechanisms underlying the observed effects of these compounds on mouse lung microvascular endothelial cells. The measured parameters include permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology. Two phenanthrene compounds, 2,7-dihydroxy-4,6-dimethoxyphenanthrene (1) and 6,7-dihydroxy-2,4-dimethoxyphenanthrene (2) were isolated from peels. Both these phenanthrene compounds exhibited significant scavenging activity against PM-induced ROS and inhibited ROS-induced activation of p38 mitogen-activated protein kinase. In addition, enhancement of Akt pathway, involved in the maintenance of endothelial integrity, was noted. These phenanthrene compounds also reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid obtained from PM-induced lung tissues. Evidence thus indicates that phenanthrene compounds derived from may exhibit protective effects against PM-induced inflammatory lung injury and vascular hyperpermeability in mice.
颗粒物 2.5（PM），空气动力学直径≤2.5μm，是主要的空气污染物，与血管屏障完整性丧失引起的肺损伤有关，起着关键作用。山药，是薯蓣科多年生草本植物，广泛种植于亚洲热带和亚热带地区。其地上部分和根茎均可食用，具有营养和药用价值。本研究的目的是：（1）鉴定山药皮中可能具有抑制 PM 诱导的小鼠肺炎症作用的生物活性化合物；（2）研究这些化合物对小鼠肺微血管内皮细胞的作用机制。测量的参数包括通透性、白细胞迁移、促炎蛋白激活、活性氧（ROS）生成和组织学。从山药皮中分离得到两种菲类化合物，2,7-二羟基-4,6-二甲氧基菲（1）和 6,7-二羟基-2,4-二甲氧基菲（2）。这两种菲类化合物均对 PM 诱导的 ROS 表现出显著的清除活性，并抑制 ROS 诱导的 p38 丝裂原活化蛋白激酶的激活。此外，还观察到与维持内皮完整性有关的 Akt 通路的增强。这些菲类化合物还减少了 PM 诱导的肺组织中支气管肺泡灌洗液中的血管蛋白渗漏、白细胞浸润和促炎细胞因子的释放。这些证据表明，山药皮中的菲类化合物可能对 PM 诱导的炎症性肺损伤和小鼠血管通透性增加具有保护作用。
