Baek Jin Ah, Lee Yang Deok, Lee Chan Bog, Go Hyeon Kyu, Kim Jin Pyo, Seo Jeong Ju, Rhee Yang Keun, Kim A Mi, Na Dong Jib
Department of Internal Medicine, Eulji University School of Medicine, Seo-Gu, Daejeon, Republic of Korea.
Nitric Oxide. 2009 Mar;20(2):122-8. doi: 10.1016/j.niox.2008.10.003. Epub 2008 Oct 17.
Nitric oxide (NO) is a marker of pulmonary inflammation. In asthma, the levels of exhaled NO are elevated and the source of this increased NO is inducible nitric oxide synthase (iNOS) within airway epithelial cells. Epimagnolin and fargesin are compounds isolated from the ethanol extract of Magnoliae flos, the seed of the Magnolia plant and are used to treat nasal congestion, headache and sinusitis in Asian countries. This study investigated whether epimagnolin and fargesin inhibit extracellular signal-regulated kinase (ERK) activation and decrease iNOS expression and NO production in stimulated human respiratory epithelial cells. An immortal Type II alveolar cell line of human origin (A549) was stimulated by cytomix (CM), composed of IL-1beta, TNF-alpha and IFN-gamma, with or without concurrent exposure to M. flos extract (epimagnolin or fargesin). CM-induced levels of NO production, iNOS expression and ERK activation were evaluated. A549 cells stimulated with CM showed increases in iNOS mRNA and protein expression, and NO synthesis. However, treatment with epimagnolin or fargesin decreased levels of iNOS mRNA and protein expression, and NO synthesis. CM stimulated a rapid increase in the activity of ERK, whereas epimagnolin and fargesin inhibited ERK phosphorylation. Epimagnolin and fargesin inhibit iNOS expression and decrease production of NO via ERK pathway in cytokine-stimulated human respiratory epithelial cells.
一氧化氮（NO）是肺部炎症的一个标志物。在哮喘中，呼出的NO水平会升高，而这种增加的NO来源是气道上皮细胞内的诱导型一氧化氮合酶（iNOS）。表木兰脂素和辛夷脂素是从木兰科植物种子的辛夷乙醇提取物中分离出的化合物，在亚洲国家用于治疗鼻塞、头痛和鼻窦炎。本研究调查了表木兰脂素和辛夷脂素是否能抑制细胞外信号调节激酶（ERK）的激活，并降低细胞因子刺激的人呼吸道上皮细胞中iNOS的表达和NO的产生。用人源永生II型肺泡细胞系（A549），在有或无同时暴露于辛夷提取物（表木兰脂素或辛夷脂素）的情况下，用由白细胞介素-1β、肿瘤坏死因子-α和干扰素-γ组成的细胞混合物（CM）进行刺激。评估CM诱导的NO产生水平、iNOS表达和ERK激活情况。用CM刺激的A549细胞显示iNOS mRNA和蛋白表达以及NO合成增加。然而，用表木兰脂素或辛夷脂素处理可降低iNOS mRNA和蛋白表达水平以及NO合成。CM刺激ERK活性迅速增加，而表木兰脂素和辛夷脂素抑制ERK磷酸化。表木兰脂素和辛夷脂素通过ERK途径抑制细胞因子刺激的人呼吸道上皮细胞中iNOS的表达并减少NO的产生。
