Niu Xiaofeng, Wang Yu, Li Weifeng, Mu Qingli, Li Huani, Yao Huan, Zhang Hailin
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, PR China.
Int Immunopharmacol. 2015 Feb;24(2):432-439. doi: 10.1016/j.intimp.2014.12.041. Epub 2015 Jan 13.
Acute lung injury (ALI) is a life-threatening disease characterized by serious lung inflammation and increased capillary permeability, which presents a high mortality worldwide. Isofraxidin (IF), a Coumarin compound isolated from the natural medicinal plants such as Sarcandra glabra and Acanthopanax senticosus, has been reported to have definite anti-bacterial, anti-oxidant, and anti-inflammatory activities. However, the effects of IF against lipopolysaccharide-induced ALI have not been clarified. The aim of the present study is to explore the protective effects and potential mechanism of IF against LPS-induced ALI in mice. In this study, We found that pretreatment with IF significantly lowered LPS-induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in serum and bronchoalveolar lavage fluid (BALF). We also found that total cells, neutrophils and macrophages in BALF, MPO activity in lung tissues were markedly decreased. Besides, IF obviously inhibited lung histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These results suggest that IF has a protective effect against LPS-induced ALI, and the protective effect of IF seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2.
急性肺损伤（ALI）是一种危及生命的疾病，其特征为严重的肺部炎症和毛细血管通透性增加，在全球范围内具有较高的死亡率。异嗪皮啶（IF）是从九节龙和刺五加等天然药用植物中分离出的一种香豆素化合物，据报道具有明确的抗菌、抗氧化和抗炎活性。然而，IF对脂多糖诱导的ALI的影响尚未阐明。本研究的目的是探讨IF对小鼠脂多糖诱导的ALI的保护作用及潜在机制。在本研究中，我们发现IF预处理可显著降低脂多糖诱导的死亡率和肺湿重与干重（W/D）比值，并降低血清和支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和前列腺素E2（PGE2）的水平。我们还发现BALF中的总细胞、中性粒细胞和巨噬细胞以及肺组织中的MPO活性均明显降低。此外，IF明显抑制肺组织病理学变化和环氧化酶-2（COX-2）蛋白表达。这些结果表明，IF对脂多糖诱导的ALI具有保护作用，且IF的保护作用似乎源于对肺组织中COX-2蛋白表达的抑制，从而调节PGE2的产生。
