Costunolide inhibits pulmonary fibrosis via regulating NF-kB and TGF-β1/Smad2/Nrf2-NOX4 signaling pathways
Costunolide inhibits pulmonary fibrosis via regulating NF-kB and TGF-β1/Smad2/Nrf2-NOX4 signaling pathways
复制标题
Costunolide 通过调节 NF-kB 和 TGF-beta(1)/Smad(2)/Nrf(2)-NOX4 信号通路抑制肺纤维化
DOI：
10.1016/j.bbrc.2019.01.104
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发表时间：
2019-03-05
影响因子：
3.1
通讯作者：
Wang, Taoyuan
中科院分区：
文献类型：
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作者：
Liu, Bin;Rong, Yumei;Wang, Taoyuan
具体研究香附内酯(CN)的抑制作用及相关机制对肺纤维化的治疗具有重要意义。在此，我们研究了香附内酯在体内和体外治疗肺纤维化的药理活性。在体内实验中，首先于0天气管内注射博莱霉素(BLM，5 mg/kg)造成小鼠肺纤维化。从第2天到第21天，给小鼠灌胃不同剂量的CN(低剂量(CNL)：10 mg/kg，高剂量(CNH)：20 mg/kg)和吡非尼酮(PFD)(阳性对照，50 mg/kg)。在体外细胞模型中，细胞与重组人转化生长因子-β1孵育24小时，形成转化生长因子-β(1)诱导的肺纤维化。细胞经不同处理24 h后，随机分为5组。通过体内、外相关蛋白的表达水平和氧化应激因子来评价CN的活性，并从涉及的通道蛋白方面探讨CN的作用机制。因此，通过比较吡非尼酮组和CN组的α-SMA、I型/III型胶原、HYP、MDA、SOD等多项指标，揭示CN对博莱姆诱导的肺纤维化和转化生长因子-β(1)诱导的肺纤维化有一定的保护作用。此外，我们的研究还证明CN可能通过抑制NF-kB依赖的炎症反应，调节转化生长因子-β(1)/Smad(2)/NOX4-NRF(2)信号通路而发挥作用。综上所述，CN可能是未来治疗肺纤维化的潜在候选药物。(C)2019 Elsevier Inc.保留所有权利。
Specific study about the inhibitory effect of costunolide (CN) and relevant mechanism is of great significance for the treatment of pulmonary fibrosis. Here, the pharmacological activity of costunolide on the treatment of pulmonary fibrosis was investigated in vivo and in vitro. The in vivo mice study, mice were received intratracheal injection of bleomycin (BLM, 5 mg/kg) on 0 day to obtain BLM-induced pulmonary fibrosis firstly. From 2 day to 21 day, mice were orally administered with different dose of CN (low dose(CNL): 10 mg/kg, high dose(CNH): 20 mg/kg) and pirfenidone (PFD)(positive control, 50 mg/ kg). The in vitro cells model, cells were incubated with recombinant human TGF-beta 1 for 24 h to get TGF-beta(1)-induced pulmonary fibrosis. Cells were treated differently for 24 h and divided into five groups. Then, the activity of CN was evaluated by the expression level of related protein and the factors of oxidative stress in vivo and in vitro, and the mechanism was tested from the involved channel protein aspect. As a result, from the comparison of multiple factors (alpha-SMA, collagen type I/III, HYP, MDA, SOD) between pirfenidone group and CN group, it revealed the beneficial effects of CN against BLM-induced and TGF-beta(1)-induced pulmonary fibrosis. In addition, our study also proved that CN exerted its effects through suppressing the NF-kB dependent inflammation and regulated TGF-beta(1)/Smad(2)/ NOX4-Nrf(2) signaling pathways. In conclusion, CN could be a potential theraputic candidate for the treatment pulmonary fibrosis in the future. (C) 2019 Elsevier Inc. All rights reserved.