β-Patchoulene from patchouli oil protects against LPS-induced acute lung injury via suppressing NF-κB and activating Nrf2 pathways
β-Patchoulene from patchouli oil protects against LPS-induced acute lung injury via suppressing NF-κB and activating Nrf2 pathways
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DOI：
10.1016/j.intimp.2017.07.001
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发表时间：
2017-09-01
影响因子：
5.6
通讯作者：
Li, Yu-Cui
中科院分区：
文献类型：
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作者：
Chen, Xiao-Ying;Dou, Yao-Xing;Li, Yu-Cui
β-广藿香烯（β-PAE），一种从广藿香（Pogostemon cablin（布兰科）Benth.）的叶和茎的精油中分离的三环倍半萜，据报道具有有效的抗炎活性。本研究旨在评价β-PAE对脂多糖（LPS）诱导的小鼠急性肺损伤（ALI）的潜在保护作用，并阐明其潜在机制。肺内滴注内毒素（LPS）诱导ALI，地塞米松（DEX）作为阳性对照。结果表明，与模型组相比，β-PAE预处理组小鼠死亡率明显降低，肺W/D比值明显降低，肺组织病理改变明显减轻。同时，β-PAE预处理显著抑制支气管肺泡灌洗液中TNF-α、IL-6和IL-1 β分泌的增加，并阻止LPS诱导的肺MPO活性和MDA水平的升高。此外，β-PAE预处理显着增加了miR-146 a的表达，并抑制了LPS诱导的NF-κ B活化及其介导的基因（TNF-α、IL-6和IL-1 β）的表达。还观察到β-PAE显著上调Nrf 2和HO-1表达并激活抗氧化基因（NQO-1、GCLC和HO-1）。结论：β-PAE对LPS诱导的ALI具有保护作用，其机制可能与其差异调节NF-κ B B和Nrf 2活性及上调miR-146 a表达有关。这些结果使β-PAE成为一种有前途的抗炎剂，值得进一步开发为治疗ALI的药物。
beta-Patchoulene (beta-PAE), a tricyclic sesquiterpene isolated from the essential oil of the leaves and stems of Pogostemon cablin (Blanco) Benth., has been reported to have potent anti-inflammatory activity. The aim of this study was to evaluate the potential protective effect of beta-PAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. ALI was induced by intracheal instillation of LPS into lung, and dexamethasone (DEX) was used as a positive control. Results indicated that pretreatment with beta-PAE significantly decreased the mortality rate of mice and lung W/D weight ratio, ameliorated lung pathological changes as compared to model group. Meanwhile, beta-PAE pretreatment markedly inhibited the increase of TNF-alpha, IL-6 and IL-1 beta secretions in the bronchoalveolar lavage fluid, and prevented LPS-induced elevations of MPO activity and MDA level in the lung. Additionally, beta-PAE pretreatment significantly elevated miR-146a expression and suppressed the LPS-induced activation of NF-kappa B and expression of its mediated genes (TNF-alpha, IL-6 and IL-1 beta). beta-PAE was also observed to markedly upregulate the Nrf2 and HO-1 expression and activate the antioxidant genes (NQO-1, GCLC and HO-1). Taken together, beta-PAE possessed protective effect against LPS-induced ALI, which might be associated with its differential regulation of NF-kappa B and Nrf2 activities and upregulation of expression of miR-146a. The results rendered beta-PAE a promising anti-inflammatory agent worthy of further development into a pharmaceutical drug for the treatment of ALI.