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Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway

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Abstract

Pseudomonas aeruginosa is 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 of P. 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 against P. aeruginosa pneumonia, which was further validated via in vivo and in vitro experiments. The in vivo experiments demonstrated that quercetin alleviated the P. 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 upon P. aeruginosa infection. Altogether, this study suggested that quercetin reduced the P. aeruginosa-induced acute lung inflammation by suppressing PI3K/AKT/NF-κB signaling pathway.

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Funding

This study was funded by the National Natural Science Foundation of China (Grant No.: 82002112).

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Authors and Affiliations

  1. Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, 4655 University Road, Jinan, 250355, China

    Xiaolei Jia, Mengdi Gu, Jiangqin Dai, Jue Wang & Zheng Pang

  2. School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, 4655 University Road, Jinan, 250355, China

    Yingying Zhang

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  1. Xiaolei Jia
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  2. Mengdi Gu
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  3. Jiangqin Dai
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  4. Jue Wang
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  5. Yingying Zhang
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  6. Zheng Pang
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Contributions

XJ contributed to writing–original draft, investigation and formal analysis. MG contributed to writing–original draft, investigation and formal analysis. JD contributed to investigation and formal analysis. JW contributed to writing–review and editing. YZ contributed to methodology, supervision, project administration and writing–review and editing. ZP contributed to conceptualization, methodology, data curation, formal analysis, funding acquisition and writing–review and editing.

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Correspondence to Yingying Zhang or Zheng Pang.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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The animal experiment protocol was approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (protocol number: SDUTCM20210707002) in accordance with the Provision and General Recommendation of Chinese Experimental Animals Administration Legislation.

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Jia, X., Gu, M., Dai, J. et al. Quercetin attenuates Pseudomonas aeruginosa-induced acute lung inflammation by inhibiting PI3K/AKT/NF-κB signaling pathway. Inflammopharmacol 32, 1059–1076 (2024). https://doi.org/10.1007/s10787-023-01416-5

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