Lee Jae-Won, Park Ji-Won, Shin Na-Rae, Park So-Yeon, Kwon Ok-Kyoung, Park Hyun Ah, Lim Yourim, Ryu Hyung Won, Yuk Heung Joo, Kim Jung Hee, Oh Sei-Ryang, Ahn Kyung-Seop
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungju-si, Chungbuk 363‑883, Republic of Korea.
Int J Mol Med. 2016 Sep;38(3):834-44. doi: 10.3892/ijmm.2016.2669. Epub 2016 Jul 7.
Picrasma quassiodes (D.Don) Benn. (PQ) is a medicinal herb belonging to the family Simaroubaceae and is used as a traditional herbal remedy for various diseases. In this study, we evaluated the effects of PQ on airway inflammation using a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and LPS-stimulated raw 264.7 cells. ALI was induced in C57BL/6 mice by the intranasal administration of LPS, and PQ was administered orally 3 days prior to exposure to LPS. Treatment with PQ significantly attenuated the infiltration of inflammatory cells in the bronchoalveolar lavage fluid (BALF). PQ also decreased the production of reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BALF. In addition, PQ inhibited airway inflammation by reducing the expression of inducible nitric oxide synthase (iNOS) and by increasing the expression of heme oxygenase-1 (HO-1) in the lungs. Furthermore, we demonstrated that PQ blocked the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in the lungs of mice with LPS-induced ALI. In the LPS-stimulated RAW 264.7 cells, PQ inhibited the release of pro-inflammatory cytokines and increased the mRNA expression of monocyte chemoattractant protein-1 (MCP-1). Treatment with PQ decreased the translocation of nuclear factor (NF)-κB to the nucleus, and increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of HO-1. PQ also inhibited the activation of p38 in the LPS-stimulated RAW 264.7 cells. Taken together, our findings demonstrate that PQ exerts anti-inflammatory effects against LPS-induced ALI, and that these effects are associated with the modulation of iNOS, HO-1, NF-κB and MAPK signaling. Therefore, we suggest that PQ has therapeutic potential for use in the treatment of ALI.
苦木(Picrasma quassiodes (D.Don) Benn.,PQ)是一种属于苦木科的草药,被用作治疗各种疾病的传统草药。在本研究中,我们使用脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠模型和LPS刺激的RAW 264.7细胞,评估了PQ对气道炎症的影响。通过鼻内给予LPS在C57BL/6小鼠中诱导ALI,并在暴露于LPS前3天口服给予PQ。PQ治疗显著减轻了支气管肺泡灌洗液(BALF)中炎症细胞的浸润。PQ还降低了BALF中活性氧(ROS)和促炎细胞因子如肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6的产生。此外,PQ通过降低肺中诱导型一氧化氮合酶(iNOS)的表达并增加血红素加氧酶-1(HO-1)的表达来抑制气道炎症。此外,我们证明PQ可阻断LPS诱导的ALI小鼠肺中丝裂原活化蛋白激酶(MAPK)和核因子-κB(NF-κB)的激活。在LPS刺激的RAW 264.7细胞中,PQ抑制促炎细胞因子的释放并增加单核细胞趋化蛋白-1(MCP-1)的mRNA表达。PQ治疗减少了核因子(NF)-κB向细胞核的转位,并增加了核因子红细胞2相关因子2(Nrf2)的核转位和HO-1的表达。PQ还抑制了LPS刺激的RAW 264.7细胞中p38的激活。综上所述,我们的研究结果表明PQ对LPS诱导的ALI具有抗炎作用,并且这些作用与iNOS、HO-1、NF-κB和MAPK信号通路的调节有关。因此,我们认为PQ在ALI治疗中具有治疗潜力。