A novel chalcone derivative, L2H17, ameliorates lipopolysaccharide-induced acute lung injury via upregulating HO-1 activity.
A novel chalcone derivative, L2H17, ameliorates lipopolysaccharide-induced acute lung injury via upregulating HO-1 activity.
复制标题
DOI：
10.1016/j.intimp.2019.02.002
复制
发表时间：
2019-06
影响因子：
5.6
通讯作者：
Yuting Lin;Danping Qiu;Lili Huang;Sangsang Zhang;Chenjian Song;Beibei Wang;Jianzhang Wu;
中科院分区：
文献类型：
--
作者：
Yuting Lin;Danping Qiu;Lili Huang;Sangsang Zhang;Chenjian Song;Beibei Wang;Jianzhang Wu;
研究背景查尔酮是一种天然产物，具有广泛的生物活性。 L2H17是我们前期研究中合成并筛选的一种查尔酮衍生物，在体外表现出优异的抗炎特性。本研究探讨了L2H17对脂多糖（LPS）诱导的急性肺损伤（ALI）的治疗潜力以及血红素加氧酶-1（HO-1）的作用。材料与方法采用LPS（10mg/kg）气管内滴注诱导ALI动物模型。使用苏木精和伊红 (HE) 染色确定 L2H17 对 LPS 诱导的结构损伤的影响，并检查组织水肿程度。收集支气管肺泡灌洗液（BALF），通过酶联免疫吸附测定（ELISA）评估相关细胞因子的水平，并评估超氧化物歧化酶（SOD）活性。使用免疫组织化学和蛋白质印迹法测定 HO-1 表达。研究L2H17对RAW 264.7中LPS刺激的影响以及HO-1通路的参与。结果L2H17减轻了组织病理学表现和组织水肿。此外，L2H17 减少 BALF 中促炎因子的产生并增加 SOD 活性。在体外，L2H17 显着减少促炎细胞因子的产生。此外，L2H17 提高了 LPS 处理的肺组织和 RAW 264.7 中 HO-1 的表达。我们还发现L2H17对炎症反应的抑制作用被HO-1活性抑制剂锡原卟啉IX（SnPP）减弱。结论我们的数据证实L2H17可以通过抑制炎症反应和调节HO-1途径在体外和体内对ALI发挥保护作用。
BackgroundChalcone, a natural product, has a wide range of biological activities. L2H17, a chalcone derivative, was synthesized and screened in our previous study and exhibited excellent anti-inflammatory property in vitro. This study investigated the therapeutic potential of L2H17 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the role of heme oxygenase-1 (HO-1).Materials and methodsAn ALI animal model was induced by LPS (10 mg/kg) intratracheal instillation. The effect of L2H17 on LPS-induced structural damage was determined using hematoxylin and eosin (HE) staining, and tissue edema extent was examined. Bronchoalveolar lavage fluid (BALF) was harvested to assess the levels of related cytokines by enzyme-linked immunosorbent assay (ELISA), and superoxide dismutase (SOD) activity was also assessed. HO-1 expression was determined using immunohistochemistry and western blotting. The effects of L2H17 on LPS stimulation in RAW 264.7 and the involvement of the HO-1 pathway were investigated.ResultsL2H17 alleviated the histopathological manifestations and tissue edema. Moreover, L2H17 decreased the production of pro-inflammatory factors in BALF and increased SOD activity. In vitro, L2H17 significantly reduced pro-inflammatory cytokine production. Additionally, L2H17 improved the expression of HO-1 in LPS-treated lung tissue and RAW 264.7. We also found that the inhibitory effect of L2H17 on the inflammatory responses was attenuated by an inhibitor of HO-1 activity, Tin protoporphyrin IX (SnPP).ConclusionOur data confirmed that L2H17 can exert protective effect on ALI in vitro and in vivo by inhibiting inflammatory responses and modulating the HO-1 pathway.