West China School of Basic Medical Science and Forensic Medicine, Sichuan University, No.17, Section3, Renmin South Road, Chengdu, 610044, People's Republic of China.
Department of Medical Oncology, West China Hospital, Cancer Center, Sichuan University, No.37 Guoxue Lane, Chengdu, 610041, China.
Sci Rep. 2024 Sep 8;14(1):20913. doi: 10.1038/s41598-024-71569-y.
Cytokine storm (CS) emerges as an exacerbated inflammatory response triggered by various factors such as pathogens and excessive immunotherapy, posing a significant threat to life if left unchecked. Quercetin, a monomer found in traditional Chinese medicine, exhibits notable anti-inflammatory and antiviral properties. This study endeavors to explore whether quercetin intervention could mitigate CS through a combination of network pharmacology analysis and experimental validation. First, common target genes and potential mechanisms affected by quercetin and CS were identified through network pharmacology, and molecular docking experiments confirmed quercetin and core targets. Subsequently, in vitro experiments of Raw264.7 cells stimulated by lipopolysaccharide (LPS) showed that quercetin could effectively inhibit the overexpression of pro-inflammatory mediators and regulate the AKT1-FoxO1 signaling pathway. At the same time, quercetin can reduce ROS through the Keap1-Nrf2 signaling pathway. In addition, in vivo studies of C57BL/6 mice injected with LPS further confirmed quercetin's inhibitory effect on CS. In conclusion, this investigation elucidated novel target genes and signaling pathways implicated in the therapeutic effects of quercetin on CS. Moreover, it provided compelling evidence supporting the efficacy of quercetin in reversing LPS-induced CS, primarily through the regulation of the AKT1-FoxO1 and Keap1-Nrf2 signaling pathways.
细胞因子风暴（CS）是一种由各种因素（如病原体和过度免疫治疗）引发的过度炎症反应，如果不加以控制，会对生命构成严重威胁。槲皮素是一种在传统中药中发现的单体，具有显著的抗炎和抗病毒特性。本研究旨在通过网络药理学分析和实验验证相结合的方法，探讨槲皮素干预是否可以减轻 CS。首先，通过网络药理学确定了槲皮素和 CS 共同影响的常见靶基因和潜在机制，并通过分子对接实验验证了槲皮素和核心靶标。随后，体外实验表明，槲皮素可以有效抑制 LPS 刺激的 Raw264.7 细胞中促炎介质的过度表达，并调节 AKT1-FoxO1 信号通路。同时，槲皮素可以通过 Keap1-Nrf2 信号通路减少 ROS。此外，用 LPS 注射的 C57BL/6 小鼠的体内研究进一步证实了槲皮素对 CS 的抑制作用。总之，本研究阐明了槲皮素治疗 CS 的作用机制涉及的新靶基因和信号通路。此外，它为槲皮素通过调节 AKT1-FoxO1 和 Keap1-Nrf2 信号通路逆转 LPS 诱导的 CS 提供了有力证据。
