Department of Biomaterials Science (BK21 FOUR program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute/Laboratory Animals Resources Center, Pusan National University, Miryang, Korea.
Department of Biological Science, Universidad de Concepcion Edmundo Larenas, Concepcion, Chile.
Pharm Biol. 2020 Dec;58(1):1263-1276. doi: 10.1080/13880209.2020.1856146.
The natural products derived from H.H. Iltis (Capparaceae) could have great potential for anti-inflammation since they inhibited the inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.
This study investigated the anti-inflammatory effects and related mechanism of methanol extract of leaves (MCE) during atopic dermatitis (AD) responses.
Alterations in the phenotypical markers for AD, luciferase signal, iNOS-mediated COX-2 induction pathway, and inflammasome activation were analysed in non-Tg (n = 5) and 15% phthalic anhydride (PA) treated IL-4/Luc/CNS-1 transgenic (Tg) HR1 mice (n = 5 per group), subsequent to treatment with acetone-olive oil (AOO), vehicle (DMSO) and two dose MCE (20 and 40 mg/kg) three times a week for 4 weeks.
MCE treatment reduced the intracellular ROS level (48.2%), NO concentration (7.1 mmol/L) and inflammatory cytokine expressions (39.1%) in the LPS-stimulated RAW264.7 cells. A significant decrease was detected for ear thickness (16.9%), weight of lymph node (0.7 mg), IgE concentration (1.9 µg/mL), and epidermal thickness (31.8%) of the PA + MCE treated Tg mice. MCE treatment induced the decrease of luciferase signal derived from the IL-4 promoter and the recovery of the IL-4 downstream regulator cytokines. PA + MCE treated Tg mice showed decreasing infiltration of mast cells (42.5%), iNOS-mediated COX-2 induction pathway, MAPK signalling pathway and inflammasome activation in the ear tissue.
These findings provide the first evidence that MCE may have great potential to suppress chemical-induced skin inflammation through the suppression of IL-4 cytokine and the iNOS-mediated COX-2 induction pathway, and activation of inflammasome.
H.H. Iltis（山柑科）中天然产物具有很强的抗炎潜力，因为它们可以抑制脂多糖（LPS）刺激的 RAW 264.7 细胞中的炎症反应。
本研究探讨了山柑属叶甲醇提取物（MCE）在特应性皮炎（AD）反应中的抗炎作用及相关机制。
在非转（n=5）和 15%邻苯二甲酸酐（PA）处理的 IL-4/Luc/CNS-1 转基因（Tg）HR1 小鼠（每组 5 只）中，分析 AD 表型标志物、荧光素酶信号、iNOS 介导的 COX-2 诱导途径和炎症小体激活的变化，随后用丙酮-橄榄油（AOO）、溶剂（DMSO）和两种剂量 MCE（20 和 40mg/kg）每周三次处理 4 周。
MCE 处理降低了 LPS 刺激的 RAW264.7 细胞中细胞内 ROS 水平（48.2%）、NO 浓度（7.1mmol/L）和炎症细胞因子表达（39.1%）。在 PA+MCE 处理的 Tg 小鼠中，耳厚度（16.9%）、淋巴结重量（0.7mg）、IgE 浓度（1.9μg/mL）和表皮厚度（31.8%）显著降低。MCE 处理诱导 IL-4 启动子衍生的荧光素酶信号减少和 IL-4 下游调节剂细胞因子的恢复。PA+MCE 处理的 Tg 小鼠耳组织中 mast 细胞浸润减少（42.5%）、iNOS 介导的 COX-2 诱导途径、MAPK 信号通路和炎症小体激活减少。
这些发现首次提供了证据，表明 MCE 可能通过抑制 IL-4 细胞因子和 iNOS 介导的 COX-2 诱导途径以及炎症小体的激活，具有抑制化学诱导皮肤炎症的巨大潜力。
