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
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
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DOI：
10.1039/c9fo01984g
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发表时间：
2020-03-01
期刊：
影响因子：
6.1
通讯作者：
Ci, Xinxin
中科院分区：
文献类型：
--
作者：
Gao, Yun;Lv, Xiaohong;Ci, Xinxin
胸膜炎是指由刺激胸膜的致病因素引起的胸膜疾病，与胸膜炎症和氧化应激有关。异甘草素（Isoliquiritigenin，ISL）是从甘草中提取的一种黄酮类化合物，具有抗氧化和抗炎作用。在本研究中，我们研究了ISL对角叉菜胶诱导的小鼠胸膜炎和肺损伤的保护作用。小鼠腹腔注射ISL（30 mg kg（-1））两次（每次间隔12小时），然后在第二次注射ISL后1小时暴露于Car。我们的研究结果表明，ISL治疗显着减轻角叉菜胶诱导的组织病理学损伤和增加水平的炎性细胞渗出，蛋白质泄漏，和促炎介质。同时，ISL抑制角叉菜胶诱导的活性氧（ROS）产生、MDA和MPO的生成以及SOD和GSH的耗竭。此外，它还降低了GSSG水平和GSSG/GSH比值。其作用机制是通过抑制NOX 2和NOX 4水平，使KEAP-1和Nrf 2解离，激活下游基因HO-1、NQO 1、GCLC和GCLM，从而减轻氧化应激。此外，ISL通过抑制NOD样受体蛋白3（NLRP 3）/NF-κ B通路以及高水平的iNOS和考克斯-2发挥抗炎保护作用。总之，我们的研究结果加强了这样的假设，即ISL对角叉菜胶诱导的胸膜炎和肺损伤发挥保护作用的方式，可以归因于Nrf 2介导的抗氧化活性和NLRP 3/NF-κ B介导的抗炎活性。
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-kappa B 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-kappa B-mediated anti-inflammatory activities.