Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar;83(1):1097-1104.
doi: 10.1007/s12013-024-01544-x. Epub 2024 Sep 24.

Cinnamaldehyde Alleviates Alveolar Epithelial Cell Injury in ALI by Inhibiting the CaMKII Pathway

Lei Liu #  1 , Hao Zhang #  2 , Siming Chen #  2 , Wankang Dian #  2 , Zhou Zheng #  2
Affiliations

Cinnamaldehyde Alleviates Alveolar Epithelial Cell Injury in ALI by Inhibiting the CaMKII Pathway

Lei Liu et al. Cell Biochem Biophys. 2025 Mar.

Erratum in

Abstract

Alveolar epithelial cell injury plays a key role in acute lung injury (ALI) and is a vital determinant of its severity. Here, we aimed to assess the protective effects of cinnamaldehyde (CA) on lipopolysaccharide (LPS)-induced A549 cells and elucidate the underlying mechanisms. A549 cells were stimulated with 1 μg/mL LPS for 24 h to establish an alveolar epithelial cell injury model and subsequently treated with CA or Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and lactate dehydrogenase release assays were used to evaluate apoptosis, cell viability, and lactate dehydrogenase activity, respectively. Levels of inflammatory cytokines (interleukin-6, interleukin-1β, tumor necrosis tactor-α, and interferon-γ) and oxidative stress markers (reactive oxygen species, superoxide dismutase, catalase, and malondialdehyde) were determined using enzyme-linked immunosorbent assay and specific assay kits, respectively. Furthermore, levels of apoptosis-related proteins (cleaved caspase-3, Bcl-2-associated X, and Bcl-2) and CaMKII were assessed via western blotting. CA did not exhibit significant cytotoxicity in A549 cells. It dose-dependently improved the cell viability, suppressed apoptosis, decreased cleaved caspase-3 and Bcl-2-associated X levels, and increased Bcl-2 levels in LPS-treated A549 cells. It also inhibited inflammatory factor release and oxidative stress in LPS-induced A549 cells. Similar results were observed in the KN93- and CA-treated groups. Western blotting assay revealed that CA and KN93 inhibited CaMKII pathway activation, as indicated by the reduced p-CaMKII and p-phospholamban (PLN) levels and p-CaMKII/CaMKII and p-PLN/PLN ratios. Overall, CA alleviated alveolar epithelial cell injury by inhibiting the inflammatory response and oxidative stress and inducing cell apoptosis in LPS-induced A549 cells by regulating the CaMKII pathway, serving as a potential candidate for ALI prevention and treatment.

Keywords: Acute lung injury; CaMKII pathway; Cinnamaldehyde.

PubMed Disclaimer

Conflict of interest statement

Compliance with Ethical Standards. Conflict of interest: The authors declare no competing interests.

References

    1. Xia, D., Wang, S., Liu, A., Li, L., Zhou, P. & Xu, S. (2022). CCL25 inhibition alleviates sepsis-induced acute lung injury and inflammation. Infection and Drug Resistance, 15, 3309–3321. https://doi.org/10.2147/IDR.S352544 . - DOI - PubMed - PMC
    1. Xu, X., Zhu, Q., Niu, F., Zhang, R., Wang, Y., Wang, W., Sun, D., Wang, X., & Wang, A. (2018). A2BAR activation attenuates acute lung injury by inhibiting alveolar epithelial cell apoptosis both in vivo and in vitro. American Journal of Physiology-Cell Physiology, 315, C558–C570. https://doi.org/10.1152/ajpcell.00294.2017 . - DOI - PubMed
    1. Zhao, J., Zhen, N., Zhou, Q., Lou, J., Cui, W., Zhang, G., & Tian, B. (2023). Nets promote inflammatory injury by activating cgas-sting pathway in acute lung injury. International Journal of Molecular Sciences, 24, 5125. https://doi.org/10.3390/ijms24065125 . - DOI - PubMed - PMC
    1. Jiang, Z. F., Zhang, L., & Shen, J. (2020). MicroRNA: Potential biomarker and target of therapy in acute lung injury. Human & Experimental Toxicology, 39, 1429–1442. https://doi.org/10.1177/0960327120926254 . - DOI
    1. Villalobo, A. (2018). The multifunctional role of phospho-calmodulin in pathophysiological processes. Biochemical Journal, 475, 4011–4023. https://doi.org/10.1042/BCJ20180755 . - DOI - PubMed

MeSH terms

LinkOut - more resources