Amentoflavone Ameliorates Carrageenan-Induced Pleurisy and Lung Injury by Inhibiting the NF-κB/STAT3 Pathways via Nrf2 Activation.
Amentoflavone Ameliorates Carrageenan-Induced Pleurisy and Lung Injury by Inhibiting the NF-κB/STAT3 Pathways via Nrf2 Activation.
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DOI：
10.3389/fphar.2022.763608
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发表时间：
2022
影响因子：
5.6
通讯作者：
Peng L
中科院分区：
文献类型：
--
作者：
Hou T;Yang M;Yan K;Fan X;Ci X;Peng L
许多天然黄酮类化合物可以激活核因子红细胞2相关因子2（Nrf 2），这对于缓解与炎症和氧化应激相关的各种疾病（包括胸膜炎）至关重要。穗花杉双黄酮（Amentoflavone，AMF）是一种从多种植物中提取的黄酮类化合物，具有良好的生物活性，尤其是抗炎和抗氧化活性。我们的目的是研究AMF是否通过激活Nrf 2来保护角叉菜胶（Car）诱导的胸膜炎和肺损伤。在野生型（WT）和Nrf 2缺陷型（Nrf 2-/-）小鼠中诱导胸膜炎。收集胸膜渗出液和肺组织进行生化分析、H&E染色、免疫细胞化学和Western印迹。我们的研究结果表明，AMF保护汽车引起的胸膜炎和肺损伤。瑞氏-姬姆萨和H&E染色结果显示AMF可减轻炎性渗出和病理损伤。此外，AMF还能降低小鼠肺组织中SOD和GSH的消耗，降低MDA和MPO的生成。AMF通过keap-1解离激活Nrf 2，随后增加血红素加氧酶-1（HO-1）、NAD（P）H-醌氧化还原酶1（NQO 1）和γ-谷氨酰半胱氨酸连接酶（GCL）水平。AMF通过阻断Car诱导的NF-κB、信号转导和转录激活因子3（STAT 3）和细胞外信号调节激酶（ERK）通路，抑制胸腔积液中IL-1β和TNF-α的水平，升高IL-10的水平。然而，这些抗氧化和抗炎作用在Nrf 2-/-小鼠中减弱。此外，AMF未能抑制Nrf 2-/-小鼠的NF-κB和STAT 3途径。我们的研究结果表明，AMF发挥抗炎和抗氧化作用，在汽车诱导的肺损伤和胸膜炎的Nrf 2依赖的方式。
Many natural flavonoids can activate nuclear factor erythroid 2-related factor 2 (Nrf2), which is pivotal for alleviating various diseases related to inflammation and oxidative stress, including pleurisy. Amentoflavone (AMF), a biflavonoid extracted from many plants, has some beneficial bioactivities, especially anti-inflammatory and antioxidative activities. We aimed to investigate whether AMF protects against pleurisy and lung injury induced by carrageenan (Car) by activating Nrf2. Pleurisy was induced in wild-type (WT) and Nrf2-deficient (Nrf2-/-) mice. Then, pleural exudate and lung tissue were collected for biochemical analysis, H&E staining, immunocytochemistry and western blotting. Our results indicated that AMF protected against Car-induced pleurisy and lung injury. The Wright-Giemsa and H&E staining results showed that AMF alleviated inflammatory effusion and pathological injury. In addition, AMF decreased SOD and GSH depletion and MDA and MPO generation in the lung tissue of mice. AMF activated Nrf2 through keap-1 dissociation and subsequently increased heme oxygenase-1 (HO-1), NAD(P)H-quinone oxidoreductase 1 (NQO1), and γ-glutamylcysteine ligase (GCL) levels. Furthermore, AMF suppressed IL-1β and TNF-α levels and increased IL-10 levels in pleural exudate by blocking the proinflammatory NF-κB, signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) pathways induced by Car. However, these antioxidative and anti-inflammatory effects were weakened in Nrf2-/- mice. Moreover, AMF failed to suppress the NF-κB and STAT3 pathways in Nrf2-/- mice. Our results demonstrated that AMF exerted anti-inflammatory and antioxidative effects in Car-induced lung injury and pleurisy in a Nrf2-dependent manner.
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