Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.
Int J Mol Med. 2018 Jun;41(6):3353-3365. doi: 10.3892/ijmm.2018.3554. Epub 2018 Mar 9.
Acute lung injury in children is a complication showing devastating disorders linked to fibrosis progression and inflammation response. Fibrosis and inflammation response are two markers for acute lung injury. Juglanin is a natural product mainly isolated from green walnut husks of Juglans mandshurica, which isconsidered as the functional composition among a series of compounds. It exhibited effective role in various diseases by inhibiting inflammation response. In our study, the protective effects and anti-inflammatory activity of juglanin were investigated in mice and lung cells treated by lipopolysaccharide (LPS) to reveal the possible mechanism by which juglanin attenuates acute lung injury. The mice were separated into four groups. The mouse model was established with 15 mg/kg LPS injection. Juglanin dramatically reduced the inflammation of cell infiltration. Compared to mice only treated with LPS, LPS-treated mice in the presence of juglanin developed less lung fibrosis with lower levels of α-smooth muscle-actin (α-SMA), collagen type I, collagen type III, and transforming growth factor-β1 (TGF-β1). Additionally, juglanin markedly downregulated inflammatory cytokine secretion and phosphorylated nuclear factor-κB (NF-κB) expression via inhibiting IKKα/IκBα signaling pathway. Our results indicate that juglanin has a protective role in LPS-triggered acute lung injury via suppression of fibrosis and inflammation response by NF-κB signaling pathways inactivation. Thus, juglanin may be a potential candidate as dietary supplement for acute lung injury for children in future.
儿童急性肺损伤是一种严重的并发症，与纤维化进展和炎症反应有关。纤维化和炎症反应是急性肺损伤的两个标志物。胡桃醌是一种天然产物，主要从核桃绿果皮中分离得到，被认为是一系列化合物中的功能成分。它通过抑制炎症反应，在各种疾病中发挥有效作用。在本研究中，研究了胡桃醌对脂多糖（LPS）处理的小鼠和肺细胞的保护作用和抗炎活性，以揭示胡桃醌减轻急性肺损伤的可能机制。将小鼠分为四组。用 15mg/kg LPS 注射建立小鼠模型。胡桃醌显著减少细胞浸润的炎症。与仅用 LPS 处理的小鼠相比，用 LPS 处理的小鼠在存在胡桃醌的情况下，肺纤维化程度较轻，α-平滑肌肌动蛋白（α-SMA）、I 型胶原、III 型胶原和转化生长因子-β1（TGF-β1）水平较低。此外，胡桃醌通过抑制 IKKα/IκBα 信号通路，显著下调炎症细胞因子的分泌和磷酸化核因子-κB（NF-κB）的表达。我们的结果表明，胡桃醌通过抑制 NF-κB 信号通路的失活，对 LPS 触发的急性肺损伤具有保护作用，从而抑制纤维化和炎症反应。因此，胡桃醌可能成为未来儿童急性肺损伤的潜在膳食补充剂。
