Division of Nuclear Medicine, Taipei City Hospital Zhongxiao Branch, Taipei, Taiwan; Department of Biomedical Imaging and Radiological Sciences, Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
Int Immunopharmacol. 2015 Sep;28(1):270-8. doi: 10.1016/j.intimp.2015.05.051. Epub 2015 Jun 10.
Acute lung injury (ALI) has a high morbidity and mortality rate due to the serious inflammation and edema occurred in lung. Magnolol extracted from Magnolia officinalis, has been reported to exhibit anti-inflammatory, and antioxidant activities. Peroxisome proliferator-activated receptors (PPARs) are known to exert a cytoprotective effect against cellular inflammatory stress and oxidative injury. The aim of this study was to explore the involvement of PPAR-γ in the beneficial effect of magnolol in lipopolysaccharide (LPS)-induced ALI. We found that treatment with magnolol greatly improved the pathological features of ALI evidenced by reduction of lung edema, polymorphonuclear neutrophil infiltration, ROS production, the levels of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), the expression of iNOS and COX-2, and NF-κB activation in lungs exposed to LPS. Importantly, magnolol is capable of increasing the PPAR-γ expression and activity in lungs of ALI. However, blocking PPAR-γ activity with GW9662 markedly abolished the protective and anti-inflammatory effects of magnolol. Taken together, the present study provides a novel mechanism accounting for the protective effect of magnolol in LPS-induced ALI is at least partly attributed to induction of PPAR-γ in lungs, and in turn suppressing NF-κB-related inflammatory responses.
急性肺损伤 (ALI) 由于肺部严重的炎症和水肿而具有较高的发病率和死亡率。从厚朴中提取的厚朴酚已被报道具有抗炎和抗氧化作用。过氧化物酶体增殖物激活受体 (PPAR) 已知对细胞炎症应激和氧化损伤具有细胞保护作用。本研究旨在探讨 PPAR-γ 参与厚朴酚对脂多糖 (LPS) 诱导的 ALI 的有益作用。我们发现，厚朴酚治疗极大地改善了 ALI 的病理特征，表现为肺水肿减轻、多形核中性粒细胞浸润减少、ROS 产生减少、支气管肺泡灌洗液 (BALF) 中促炎细胞因子的水平降低、iNOS 和 COX-2 的表达减少以及 NF-κB 激活减少。重要的是，厚朴酚能够增加 ALI 肺组织中 PPAR-γ 的表达和活性。然而，用 GW9662 阻断 PPAR-γ 活性会显著消除厚朴酚的保护和抗炎作用。综上所述，本研究提供了一种新的机制，表明厚朴酚在 LPS 诱导的 ALI 中的保护作用至少部分归因于诱导肺组织中的 PPAR-γ，从而抑制 NF-κB 相关的炎症反应。
