A novel chalcone derivative exerts anti-inflammatory and anti-oxidant effects after acute lung injury
A novel chalcone derivative exerts anti-inflammatory and anti-oxidant effects after acute lung injury
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一种新型查尔酮衍生物在急性肺损伤后发挥抗炎和抗氧化作用
DOI：
10.18632/aging.102288
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发表时间：
2019-09-30
期刊：
影响因子：
5.2
通讯作者：
Chen, Chengshui
中科院分区：
文献类型：
--
作者：
Lin, Yuting;Zhang, Man;Chen, Chengshui
我们探讨了具有抗氧化活性的查尔酮衍生物化合物33对脂多糖（LPS）诱导的急性肺损伤（ALI）的影响。在腹腔内滴注LPS之前6小时，向小鼠灌胃给予化合物33、地塞米松或载体。24小时后，通过评估肺形态和湿/干重量比来评价化合物33对肺泡结构损伤的影响。蛋白质和促炎细胞因子水平和超氧化物歧化酶活性也检查了支气管肺泡灌洗液的无细胞上清液。此外，我们还研究了化合物33的体外抗炎和抗氧化活性及其对MAPK/NF-κB和Nrf 2/HO-1通路的影响。用化合物33预处理防止LPS诱导的结构损伤、组织水肿、蛋白质渗出和促炎介质的过度产生。化合物33的作用在大小上类似于或大于阳性对照地塞米松的作用。此外，化合物33通过抑制MAPK/NF-κB通路和激活Nrf 2/HO-1通路发挥抗炎和抗氧化作用。因此，化合物33可能是治疗ALI的有希望的候选药物。
We explored the effects of compound 33, a synthetic chalcone derivative with antioxidant activity, on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compound 33, dexamethasone or vehicle was administered intragastrically to mice 6 h before intratracheal instillation of LPS. After 24 h, the effects of compound 33 on alveolar structural damage were evaluated by assessing lung morphology and the wet/dry weight ratio. Protein and proinflammatory cytokine levels and superoxide dismutase activity were also examined in the cell free supernatant of bronchoalveolar lavage fluid. Additionally, we investigated the anti-inflammatory and antioxidant activity of compound 33 in vitro and its effects on the MAPK/NF-κB and Nrf2/HO-1 pathways. Pretreatment with compound 33 prevented LPS-induced structural damage, tissue edema, protein exudation, and overproduction of proinflammatory mediators. The effects of compound 33 were similar to or greater in magnitude than those of the positive control, dexamethasone. Moreover, compound 33 exerted anti-inflammatory and antioxidant effects in vitro by inhibiting the MAPK/NF-κB pathway and activating the Nrf2/HO-1 pathway. Compound 33 may therefore be a promising candidate treatment for ALI.