Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway
Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway
复制标题
槲皮素通过抑制PI 3 K/AKT/NF-κB信号通路减轻铜绿假单胞菌诱导的急性肺炎症
DOI：
10.1007/s10787-023-01416-5
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发表时间：
2024-02-03
影响因子：
5.8
通讯作者：
Pang，Zheng
中科院分区：
文献类型：
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作者：
Jia，Xiaolei;Gu，Mengdi;Pang，Zheng
铜绿假单胞菌是一种机会性病原体，通常在免疫功能低下的个体中引起感染，具有显著的发病率和死亡率。槲皮素是一种富含水果和蔬菜的天然类黄酮，在治疗多种疾病中具有有效的抗炎作用。然而，槲皮素治疗p的分子机制尚不清楚。铜绿菌引起的急性肺部炎症尚不清楚。在这项研究中，我们利用基于网络药理学和分子对接的方法来探索槲皮素抗stp的潜在机制。铜绿脓毒杆菌肺炎，通过体内和体外实验进一步验证。体内实验表明槲皮素对p有一定的缓解作用。通过减少中性粒细胞浸润和促炎细胞因子（IL-1β、IL-6和TNF）的产生，铜绿假单胞菌诱导的肺损伤与死亡率降低有关。此外，槲皮素处理的小鼠肺组织中PI3K、AKT、i -κB α和NF-κB p65的磷酸化水平低于未用药的小鼠。同样，体外研究表明，槲皮素预处理的巨噬细胞在p作用下，这些调节蛋白的磷酸化和促炎细胞因子的产生受到损害。aeruginosainfection。总之，这项研究表明槲皮素降低了p。铜绿假单胞菌通过抑制PI3K/AKT/NF-κB信号通路诱导急性肺炎症。
Pseudomonas aeruginosais an opportunistic pathogen that commonly causes infections in immunocompromised individuals with significant morbidity and mortality. Quercetin is a natural flavonoid abundantly present in fruits and vegetables, exerting potent anti-inflammatory effects in treatment of various diseases. However, the molecular mechanisms of quercetin in treatment ofP. aeruginosa-induced acute lung inflammation are unclear. In this study, we exploited network pharmacology- and molecular docking-based approach to explore the potential mechanisms of quercetin againstP. aeruginosapneumonia, which was further validated via in vivo and in vitro experiments. The in vivo experiments demonstrated that quercetin alleviated theP. aeruginosa-induced lung injury by diminishing neutrophil infiltration and production of proinflammatory cytokines (IL-1β, IL-6, and TNF), which was associated with decreased mortality. Moreover, the quercetin-treated mice displayed decreased phosphorylation levels of PI3K, AKT, IκBα, and NF-κB p65 in lung tissues compared to non-drug-treated mice. Similarly, the in vitro study showed that the phosphorylation of these regulatory proteins and production of the proinflammatory cytokines were impaired in the quercetin-pretreated macrophages uponP. aeruginosainfection. Altogether, this study suggested that quercetin reduced theP. aeruginosa-induced acute lung inflammation by suppressing PI3K/AKT/NF-κB signaling pathway.