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. 2025 Apr;48(2):590-606.
doi: 10.1007/s10753-024-02051-0. Epub 2024 May 24.

Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice

Liqin Zhou  1 , Yuting Lin  1 , Tengfei Zhou  2 , Yincong Xue  1 , Saverio Bellusci  3 , Mengya Shen  4 , Chengshui Chen  5   6 , Chaolei Chen  7
Affiliations

Evidence that a Novel Chalcone Derivative, Compound 27, Acts on the Epithelium Via the PI3K/AKT/Nrf2-Keap1 Signaling Pathway, to Mitigate LPS-Induced Acute Lung Injury in Mice

Liqin Zhou et al. Inflammation. 2025 Apr.

Erratum in

Abstract

Acute lung injury (ALI) is a highly heterogeneous clinical syndrome and an important cause of mortality in critically ill patients, with limited treatment options currently available. Chalcone, an essential secondary metabolite found in edible or medicinal plants, exhibits good antioxidant activity and simple structure for easy synthesis. In our study, we synthesized a novel chalcone derivative, compound 27 (C27). We hypothesized that C27 could be a potential treatment for acute respiratory distress syndrome (ARDS). Therefore, the protective effects of C27 on lung epithelial cells during ALI and the underlying molecular mechanisms were investigated. In vivo, Intratracheal instillation of LPS (10 mg/kg) was used to induce acute lung injury in mice. In vitro, the bronchial epithelial cell line (Beas-2b) was treated with 30 μM tert-butyl hydroperoxide (t-BHP) to simulate oxidative stress. Our findings demonstrate that pretreatment with C27 reduces LPS-induced oxidative destruction and cellular apoptosis in lung tissues of mice. Furthermore, it significantly attenuates t-BHP-induced cellular reactive oxygen species (ROS) generation, mitochondrial damage, and apoptosis in vitro. Mechanistically, the signaling pathway involving Nrf2-Keap1 and the downstream antioxidative proteins were activated by C27 in vivo. Additionally, PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 abolished the effect of C27 in vitro, indicating that the protective effect of C27 is mediated via the PI3K/AKT/Nrf2-Keap1 pathway. Our study provides evidence that C27 protects against LPS-induced ALI by mitigating oxidative stress via activation of the PI3K/AKT/Nrf2-Keap1 signaling pathway. Therefore, we hypothesize that C27 represents a viable alternative for ALI therapy.

Keywords: acute lung injury; apoptosis; chalcone derivatives; mitochondrial dysfunction; oxidative stress.

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Conflict of interest statement

Declarations. Ethics Approval: This study was approved by by the Wenzhou Medical University's Institutional Animal Care and Use Committee (approval no. WYDW2017-0111). Conflicts of Interest: The authors declare no conflict of interest.

References

    1. Matthay, Michael A., Rachel L. Zemans, Guy A. Zimmerman, Yaseen M. Arabi, Jeremy R. Beitler, Alain Mercat, Margaret Herridge, Adrienne G. Randolph, and Carolyn S. Calfee. 2019. Acute respiratory distress syndrome. Nature Reviews. Disease Primers 5: 18. https://doi.org/10.1038/s41572-019-0069-0 . - DOI - PubMed - PMC
    1. Mowery, Nathan T., W.T. Hillman Terzian, and Adam C. Nelson. 2020. Acute lung injury. Current Problems in Surgery 57: 100777. https://doi.org/10.1016/j.cpsurg.2020.100777 . - DOI - PubMed
    1. Bos, L.D.J., and L.B. Ware. 2022. Acute respiratory distress syndrome: causes, pathophysiology, and phenotypes. The Lancet 400: 1145–1156. https://doi.org/10.1016/S0140-6736(22)01485-4 . Elsevier. - DOI
    1. Gorman, E.A., C.M. O’Kane, and D.F. McAuley. 2022. Acute respiratory distress syndrome in adults: diagnosis, outcomes, long-term sequelae, and management. The Lancet 400: 1157–1170. https://doi.org/10.1016/S0140-6736(22)01439-8 . Elsevier. - DOI
    1. Dipayan, Chaudhuri, Sasaki Kiyoka, Karkar Aram, Sharif Sameer, Lewis Kimberly, Manoj J. Mammen, Alexander Paul, et al. 2021. Corticosteroids in COVID-19 and non-COVID-19 ARDS: A systematic review and meta-analysis. Intensive Care Medicine 47: 521–537. https://doi.org/10.1007/s00134-021-06394-2 . - DOI

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