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Costunolide attenuates LPS-induced inflammation and lung injury through inhibiting IKK/NF-κB signaling

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Abstract

Inflammation is an important pathological process of many acute and chronic diseases, such as sepsis, arthritis, and cancer. Many factors can lead to an inflammatory state of the body, among which bacterial infection plays an important role. Bacterial infection often leads to sepsis, acute lung injury (ALI), or its more serious form of acute respiratory distress syndrome, which are the main fatal diseases in intensive care units. Costunolide has been reported to possess excellent anti-inflammatory activity; however, whether it can affect inflammation induced by gram-negative bacterial is still unclear. Lipopolysaccharide (LPS) stimulated mouse peritoneal macrophages (MPMs) to release proinflammatory cytokines was used as the cell model. The mouse model of sepsis and ALI was built through injecting intravenously and intratracheally of LPS. In the present study, costunolide inhibited LPS-induced inflammatory response through IKK/NF-κB signaling pathway in macrophages. In vivo, costunolide attenuated LPS-induced septic death in mice. Meanwhile, costunolide treatment alleviated LPS-induced lung injury and inflammation via inhibiting the infiltration of inflammatory cells and the expression of inflammatory cytokines. Taken together, these results demonstrated that costunolide could attenuate gram-negative bacterial induced inflammation and diseases and might be a potential candidate for the treatment of inflammatory diseases.

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Funding

This study was supported by Zhejiang Provincial Natural Science Funding (LY23H310001 and LBY21H070001), Wenzhou Scientific and Technology Program (Y20190405 and 2018Y1220), and Wenzhou Medical University Scientific Research Projects of College Students (wyx2021101026).

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Author notes

  1. Xiaona Zhu, Bin Bai and Xiangting Ge contributed equally to this work.

Authors and Affiliations

  1. Affiliated Yueqing Hospital, Wenzhou Medical University, Wenzhou, 325600, Zhejiang, China

    Xiaona Zhu, Zhongxiang Xiao, Bing Zhang & Yali Zhang

  2. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China

    Bin Bai, Bin Zheng, Yue Tang, Letong Fang, Yelin Tang & Yali Zhang

  3. Department of Pulmonary and Critical Care Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Xiangting Ge & Yuanrong Dai

Authors
  1. Xiaona Zhu
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  2. Bin Bai
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  3. Xiangting Ge
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  5. Zhongxiang Xiao
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  9. Yuanrong Dai
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  10. Bing Zhang
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Contributions

Xiaona Zhu: Data curation, Formal analysis, Funding acquisition, Validation, Writing–original draft. Bin Bai: Formal analysis, Validation. Xiangting Ge: Formal analysis, Funding acquisition, Writing–original draft. Bin Zheng: Writing–original draft. Zhongxiang Xiao: Funding acquisition, Methodology. Yue Tang: Visualization. Letong Fang: Funding acquisition, Methodology, Visualization. Yelin Tang: Methodology, Validation. Yuanrong Dai: Writing-review & editing. Bing Zhang: Writing-review & editing. Yali Zhang: Data curation, Funding acquisition. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding authors

Correspondence to Yuanrong Dai, Bing Zhang or Yali Zhang.

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Ethical approval

All animal care and experimental procedures were approved by the Animal Policy and Welfare Committee of Wenzhou Medical University (Approval Document No. wydw2019-0438). According to the guidelines of the National Institutes of Health (NIH), all animals received humane care.

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The authors declare no competing interests.

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Zhu, X., Bai, B., Ge, X. et al. Costunolide attenuates LPS-induced inflammation and lung injury through inhibiting IKK/NF-κB signaling. Naunyn-Schmiedeberg's Arch Pharmacol 397, 1601–1610 (2024). https://doi.org/10.1007/s00210-023-02705-0

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