Choi Jinseon, Yun Seok Han, Kim Hyueyun, Lee Juhyun, Kim Seong-Man, Park Mi-Hyeong, Lee Hee Jae, Chun Wanjoo, Han Sang-Bae, Ahn Kyung-Seop, Lee Jae-Won
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju 28116, Republic of Korea.
College of Pharmacy, Chungbuk National University, Cheongju 28160, Republic of Korea.
J Microbiol Biotechnol. 2024 Nov 19;35:e2408022. doi: 10.4014/jmb.2408.08022.
Aromadendrin (ARO) is an active plant compound that exerts anti-inflammatory effects. However, its ameliorative effects on chronic obstructive pulmonary disease (COPD) remain unclear. Therefore, we investigated the inhibitory effects of ARO on bronchial inflammation using an experimental model of COPD. In vivo analysis confirmed a notable increase in the number of neutrophils/macrophages and the formation of reactive oxygen species (ROS), myeloperoxidase (MPO), interleukin (IL)-6/IL-1β, and monocyte chemoattractant protein (MCP)-1 in the bronchoalveolar lavage (BAL) fluid of COPD mice, which was attenuated by oral gavage of ARO. In addition, hematoxylin and eosin staining showed a notable cell influx in the lungs of the COPD group, which was ameliorated by ARO. Western blotting revealed that ARO decreased the upregulation of neutrophil elastase expression in the lungs of the COPD group. Furthermore, periodic acid-Schiff staining showed that increased mucus formation in the lungs of the COPD group was downregulated by ARO. ARO also blocked CREB activation in the lungs of COPD mice. This in vivo, anti-inflammatory effect of ARO was accompanied by its modulatory effect on the activation of the MAPK/NF-κB/NLRP3 inflammasome. In summary, our study demonstrated that ARO has protective effects on bronchial inflammation by attenuating immune cell accumulation, toxic molecule/cytokine/chemokine formation, and MAPK/NF-κB/NLRP3 inflammasome activation, suggesting the potential development of ARO as an adjuvant for the prevention and treatment of COPD.
香豆素(ARO)是一种具有抗炎作用的活性植物化合物。然而,其对慢性阻塞性肺疾病(COPD)的改善作用仍不清楚。因此,我们使用COPD实验模型研究了ARO对支气管炎症的抑制作用。体内分析证实,COPD小鼠支气管肺泡灌洗(BAL)液中的中性粒细胞/巨噬细胞数量、活性氧(ROS)、髓过氧化物酶(MPO)、白细胞介素(IL)-6/IL-1β和单核细胞趋化蛋白(MCP)-1显著增加,口服ARO可使其减弱。此外,苏木精和伊红染色显示COPD组肺部有明显的细胞浸润,ARO可使其改善。蛋白质印迹法显示,ARO降低了COPD组肺部中性粒细胞弹性蛋白酶表达的上调。此外,高碘酸-希夫染色显示,ARO下调了COPD组肺部增加的黏液形成。ARO还阻断了COPD小鼠肺部的CREB激活。ARO的这种体内抗炎作用伴随着其对MAPK/NF-κB/NLRP3炎性小体激活的调节作用。总之,我们的研究表明,ARO通过减轻免疫细胞积累、有毒分子/细胞因子/趋化因子形成以及MAPK/NF-κB/NLRP3炎性小体激活,对支气管炎症具有保护作用,提示ARO作为预防和治疗COPD佐剂的潜在开发价值。