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. 2025 Jul 2.
doi: 10.1007/s00210-025-04270-0. Online ahead of print.

Nobiletin's role in idiopathic pulmonary fibrosis via the PI3K/AKT/MDM2/p53 signaling pathway

Tingyuan Li #  1   2 , Jing Wang #  1   2 , Le Bai  1   2 , Qi Zhao  1   2 , Dongwei Zhu  1   2 , Yong Xu  3 , Yongsheng Wang  4 , Zhichao Wang  5 , Fanchao Feng  6 , Xianmei Zhou  7
Affiliations

Nobiletin's role in idiopathic pulmonary fibrosis via the PI3K/AKT/MDM2/p53 signaling pathway

Tingyuan Li et al. Naunyn Schmiedebergs Arch Pharmacol. .

Abstract

To explore the therapeutic effects of Nobiletin (NOB) on Idiopathic pulmonary fibrosis (IPF) and to identify its targets and molecular pathways. We verified the inhibitory effect of NOB on the senescence of A549 cells through in vitro experiments, and the inhibitory effect of NOB on the migration ability of fibroblasts was verified by the Transwell experiment. The inhibitory effects of NOB on Idiopathic IPF were subsequently assessed in a mouse model induced by bleomycin (BLM). Through PPI network, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the PI3K/AKT/MDM2/p53 signaling pathway was identified as the critical pathway. The key proteins in the signaling pathway were verified by molecular docking and western blotting. NOB showed a great inhibitory effect on A549 cell senescence and Fibroblast migration. Meanwhile, NOB reduced BLM-induced collagen deposition in mouse lung tissues and inhibited alveolar epithelial cell (AEC) senescence. Through PPI network, P53 was screened as a core target of NOB. According to functional enrichment analysis results, the PI3K/AKT signaling was believed to have played an important role. Therefore, we speculate that the PI3K/AKT/MDM2/p53 signaling pathway mediated NOB's impact on IPF. These findings were validated through molecular docking and western blotting. This study demonstrated that NOB suppressed cell senescence to protect IPF through mediating the PI3K/AKT/MDM2/p53 signaling pathway.

Keywords: Alveolar epithelial cell; Cellular senescence; Idiopathic pulmonary fibrosis; Nobiletin; P53; PI3 K/AKT signaling pathway.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Animal experimental procedures followed the Animal care and handling guidelines and got approval from the Animal Ethics Committee in Affiliated Hospital of Nanjing University of Traditional Chinese Medicine (Approval number: 2020DW-31–02). Clinical trial number: not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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References

    1. Amberger JS, Bocchini CA, Schiettecatte F, Scott AF, Hamosh A (2015) OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res 43(1):D789–D798. https://doi.org/10.1093/nar/gku1205 - DOI - PubMed
    1. American Thoracic Society (2000) Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 161(2 Pt 1):646–664. https://doi.org/10.1164/ajrccm.161.2.ats3-00
    1. Chen L, Zhang YH, Wang S, Zhang Y, Huang T, Cai YD (2017) Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS ONE 12(9):e0184129. https://doi.org/10.1371/journal.pone.0184129 - DOI - PubMed - PMC
    1. Chien SY, Hsieh MJ, Chen CJ, Yang SF, Chen MK (2015) Nobiletin inhibits invasion and migration of human nasopharyngeal carcinoma cell lines by involving ERK1/2 and transcriptional inhibition of MMP-2. Expert Opin Ther Targets 19(3):307–320. https://doi.org/10.1517/14728222.2014.992875 - DOI - PubMed
    1. Chin C, Ravichandran R, Sanborn K, Fleming T, Wheatcroft SB, Kearney MT, Tokman S, Walia R, Smith MA, Flint DJ, Mohanakumar T, Bremner RM, Sureshbabu A (2023) Loss of IGFBP2 mediates alveolar type 2 cell senescence and promotes lung fibrosis. Cell Rep Med 4(3):100945. https://doi.org/10.1016/j.xcrm.2023.100945 - DOI - PubMed - PMC

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