Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways.
Isovitexin Exerts Anti-Inflammatory and Anti-Oxidant Activities on Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting MAPK and NF-κB and Activating HO-1/Nrf2 Pathways.
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DOI：
10.7150/ijbs.13188
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发表时间：
2016
影响因子：
9.2
通讯作者：
Ci X
中科院分区：
文献类型：
--
作者：
Lv H;Yu Z;Zheng Y;Wang L;Qin X;Cheng G;Ci X
氧化损伤和炎症反应与急性肺损伤（ALI）的发病机制密切相关。因此，我们探讨了在ALI的背景下，异牡荆素（IV），糖基类黄酮的保护作用。为了实现这一点，我们分别通过将巨噬细胞暴露于脂多糖（LPS）和使用LPS诱导小鼠ALI来建立体外和体内模型。在体外，我们的结果表明，静脉注射治疗减少LPS诱导的促炎细胞因子分泌，iNOS和考克斯-2的表达，并减少ROS的产生。在体内获得了一致的结果。此外，IV抑制H2 O2诱导的细胞毒性和细胞凋亡。然而，这些作用在体外使用HO-1抑制剂后部分逆转。进一步的研究表明，IV可显着抑制RAW 264.7细胞中MAPK磷酸化，减少NF-κB核转位，并上调核因子红细胞2相关因子2（Nrf 2）和血红素加氧酶1（HO-1）的表达。在体内，IV预处理可减轻ALI的组织病理学改变，减轻多形核粒细胞浸润，减轻内皮细胞活化，降低ICAM-1和VCAM-1的表达，降低MPO和MDA的含量，升高GSH和SOD的含量。此外，IV治疗有效地增加了肺组织中Nrf 2和HO-1的表达。因此，IV可能通过抑制MAPK和NF-κB，激活HO-1/Nrf 2通路，对LPS诱导的ALI起保护作用。
Oxidative damage and inflammation are closely associated with the pathogenesis of acute lung injury (ALI). Thus, we explored the protective effect of isovitexin (IV), a glycosylflavonoid, in the context of ALI. To accomplish this, we created in vitro and in vivo models by respectively exposing macrophages to lipopolysaccharide (LPS) and using LPS to induce ALI in mice. In vitro, our results showed that IV treatment reduced LPS-induced pro-inflammatory cytokine secretion, iNOS and COX-2 expression and decreased the generation of ROS. Consistent findings were obtained in vivo. Additionally, IV inhibited H2O2-induced cytotoxicity and apoptosis. However, these effects were partially reversed following the use of an HO-1 inhibitor in vitro. Further studies revealed that IV significantly inhibited MAPK phosphorylation, reduced NF-κB nuclear translocation, and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in RAW 264.7 cells. In vivo, pretreatment with IV attenuated histopathological changes, infiltration of polymorphonuclear granulocytes and endothelial activation, decreased the expression of ICAM-1 and VCAM-1, reduced the levels of MPO and MDA, and increased the content of GSH and SOD in ALI. Furthermore, IV treatment effectively increased Nrf2 and HO-1 expression in lung tissues. Therefore, IV may offer a protective role against LPS-induced ALI by inhibiting MAPK and NF-κB and activating HO-1/Nrf2 pathways.