Obacunone mitigates ulcerative colitis-induced colonic epithelial cell injury by activating mitophagy via the PARP1/SIRT1 signaling pathway
OBJECTIVE: This study unveils how obacunone (OB) mitigates ulcerative colitis (UC)-induced colonic epithelial cell injury by activating mitophagy via the poly(ADP-ribose) polymerase 1 (PARP1)/sirtuin 1 (SIRT1) signaling pathway. - METHODS: Bioinformatics analyses and network pharmacology were utiliz...
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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
September-October 2025
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| In: |
Annals of clinical and laboratory science
Year: 2025, Jahrgang: 55, Heft: 5, Pages: 682-693 |
| ISSN: | 1550-8080 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://www.annclinlabsci.org/content/55/5/682.long
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| Verfasserangaben: | Zetao Wang, Yao Sun, Xiaohui Zhou, Jianing Shi, Lijun Shi |
| Zusammenfassung: | OBJECTIVE: This study unveils how obacunone (OB) mitigates ulcerative colitis (UC)-induced colonic epithelial cell injury by activating mitophagy via the poly(ADP-ribose) polymerase 1 (PARP1)/sirtuin 1 (SIRT1) signaling pathway. - METHODS: Bioinformatics analyses and network pharmacology were utilized to identify potential OB-related targets in UC, after which Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted. Core targets were identified via Cytoscape network modeling and machine learning algorithms. The dextran sulfate sodium (DSS)-treated human intestinal epithelium cell line (NCM460) served as an in vitro model of UC. Prior to DSS treatment, cells were pre-incubated with OB and/or the mitophagy inhibitor Mdivi-1. Furthermore, PARP1-overexpressing NCM460 cells were co-treated with OB and DSS. Cell viability and apoptosis, as well as mitochondrial reactive oxygen species (mtROS) levels were measured using the CCK-8 assay, flow cytometry, and MitoSOX Red staining, respectively. The expression of PARP1, SIRT1, PTEN-induced putative kinase 1 (PINK1), Parkin, and microtubule-associated protein 1A/1B-light chain 3 (LC3) was evaluated through Western blot analysis. - RESULTS: 145 potential targets implicated in bacterial component recognition, oxidative stress response, and inflammation/apoptosis regulation were identified after bioinformatics and network pharmacology analyses. Machine learning algorithms further refined these to five core targets (PARP1, HIF1A, PTGS2, ITGB1, and HSP90AB1), all of which demonstrated strong binding affinity with OB. In DSS-treated NCM460 cells, OB significantly improved cell viability, while reducing apoptosis and mtROS production. Mechanistic studies revealed that OB suppressed PARP1 expression while upregulating SIRT1, PINK1, Parkin, and LC3II. Notably, the protective effects of OB were abrogated by Mdivi-1 treatment or PARP1 overexpression, both of which decreased cell viability, increased apoptosis and mtROS levels, and downregulated PINK1, Parkin, and LC3II expression. - CONCLUSION: OB attenuates UC-associated epithelial damage through PARP1/SIRT1-dependent mitophagy activation. |
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| Beschreibung: | Gesehen am 25.02.2026 |
| Beschreibung: | Online Resource |
| ISSN: | 1550-8080 |