机构:[1]Sichuan Univ, West China Sch Basic Med Sci & Forens Med, 17 Sect 3,Renmin South Rd, Chengdu 610044, Peoples R China[2]Sichuan Univ, West China Hosp, Canc Ctr, Dept Med Oncol, 37 Guoxue Lane, Chengdu 610041, Peoples R China四川大学华西医院[3]Univ Elect Sci & Technol China, Canc Hosp, Sch Med, Dept Integrated Tradit Chinese & Western Med, Chengdu 610041, Peoples R China四川省肿瘤医院[4]Hainan Med Univ, Hainan Affiliated Hosp, Hainan Gen Hosp, Dept Radiat Oncol, 31 Longhua Rd, Haikou 570100, Peoples R China
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.
基金:
Tis study was supported by the National Natural Science Foundation of China (NO.82260490), Sichuan Provincial Nature Science Foundation (2022NSFSC1379); Sichuan Science and Technology Programme (2022YFSY0054)
and Technology Innovation Project of Chengdu Science and Technology (2020-YF05-00059-SN); Natural Science
Foundation of Hainan Province (NO.821QN394); Science and technology research project on novel corona-virus
pneumonia outbreak, West China Hospital, Sichuan University (HX-2019-nCoV-069).
第一作者机构:[1]Sichuan Univ, West China Sch Basic Med Sci & Forens Med, 17 Sect 3,Renmin South Rd, Chengdu 610044, Peoples R China
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推荐引用方式(GB/T 7714):
Xu Jingyi,Li Yue,Yang Xi,et al.Quercetin inhibited LPS-induced cytokine storm by interacting with the AKT1-FoxO1 and Keap1-Nrf2 signaling pathway in macrophages[J].SCIENTIFIC REPORTS.2024,14(1):doi:10.1038/s41598-024-71569-y.
APA:
Xu, Jingyi,Li, Yue,Yang, Xi,Li, Hong,Xiao, Xi...&Huang, Ying.(2024).Quercetin inhibited LPS-induced cytokine storm by interacting with the AKT1-FoxO1 and Keap1-Nrf2 signaling pathway in macrophages.SCIENTIFIC REPORTS,14,(1)
MLA:
Xu, Jingyi,et al."Quercetin inhibited LPS-induced cytokine storm by interacting with the AKT1-FoxO1 and Keap1-Nrf2 signaling pathway in macrophages".SCIENTIFIC REPORTS 14..1(2024)