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Isoliquiritigenin exerts antioxidative and anti-inflammatory effects via activating the KEAP-1/Nrf2 pathway and inhibiting the NF-κB and NLRP3 pathways in carrageenan-induced pleurisy
Food & Function ( IF 6.1 ) Pub Date : 2020/03/06 , DOI: 10.1039/c9fo01984g
Yun Gao 1, 2, 3, 4 , Xiaohong Lv 1, 2, 3, 4 , Huahong Yang 1, 2, 3, 4 , Liping Peng 1, 2, 3, 4 , Xinxin Ci 3, 4, 5, 6
Affiliation  

Pleurisy refers to a pleural disease caused by pathogenic factors that stimulate the pleura associated with pleural inflammation and oxidative stress. Isoliquiritigenin (ISL), a flavonoid from the liquorice compound, possesses antioxidative and anti-inflammatory properties. In the current study, we investigated the protective effects of ISL on carrageenan-induced pleurisy and lung injury in mice. The mice were intraperitoneally injected with ISL (30 mg kg−1) twice (each time interval of 12 h), followed by exposure to Car 1 h after the second dose of ISL. Our results indicated that ISL treatment significantly alleviated carrageenan-induced histopathological damage and increased levels of inflammatory cell exudation, protein leakage, and pro-inflammatory mediators. Meanwhile, ISL inhibited reactive oxygen species (ROS) generation, MDA and MPO formation, and SOD and GSH depletion induced by carrageenan. In addition, it decreased the GSSG level and GSSG-to-GSH ratio. In terms of the mechanism, ISL inhibited NOX2 and NOX4 levels, caused the dissociation of KEAP-1 and Nrf2, and activated the downstream genes HO-1, NQO1, GCLC and GCLM, thus decreasing oxidative stress. In addition, ISL exerts protective effects against inflammation by suppressing the NOD-like receptor protein 3 (NLRP3)/NF-κB pathway and the high levels of iNOS and COX-2. In summary, our results reinforce the hypothesis that ISL exerts protective effects on carrageenan-induced pleurisy and lung injury in a manner that can be attributed to Nrf2-mediated antioxidative activities and NLRP3/NF-κB-mediated anti-inflammatory activities.

中文翻译:

异黄体生成素通过在角叉菜胶诱发的胸膜炎中激活KEAP-1 / Nrf2途径并抑制NF-κB和NLRP3途径发挥抗氧化和抗炎作用

胸膜炎是指由致病因素引起的胸膜疾病,所述致病因素刺激与胸膜炎症和氧化应激相关的胸膜。异黄体生成素(ISL)是一种来自甘草化合物的类黄酮,具有抗氧化和抗炎特性。在当前的研究中,我们调查了ISL对角叉菜胶诱发的胸膜炎和小鼠肺损伤的保护作用。给小鼠腹膜内注射ISL(30 mg kg -1)两次(每次间隔12小时),然后在第二剂ISL后1小时暴露于Car中。我们的结果表明,ISL治疗可显着减轻角叉菜胶诱导的组织病理学损害,并增加炎症细胞渗出,蛋白质泄漏和促炎介质的水平。同时,ISL抑制了角叉菜胶诱导的活性氧(ROS)生成,MDA和MPO的形成以及SOD和GSH的消耗。此外,它降低了GSSG水平和GSSG与GSH的比率。在机制上,ISL抑制NOX2和NOX4的水平,引起KEAP-1和Nrf2的解离,并激活下游基因HO-1,NQO1,GCLC和GCLM,从而降低氧化应激。此外,ISL通过抑制NOD样受体蛋白3(NLRP3)/NF-κB途径以及高水平的iNOS和COX-2发挥抗炎症作用。总而言之,我们的结果强化了以下假设:ISL对角叉菜胶引起的胸膜炎和肺损伤具有保护作用,该作用可归因于Nrf2介导的抗氧化活性和NLRP3 /NF-κB介导的抗炎活性。
更新日期:2020-03-27
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