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7-Hydroxy-3-(4'-methoxyphenyl) coumarin (C12) attenuates bleomycin-induced acute lung injury and fibrosis through activation of SIRT3.
7-Hydroxy-3-(4'-methoxyphenyl) coumarin (C12) attenuates bleomycin-induced acute lung injury and fibrosis through activation of SIRT3.
- Source :
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Biochemical pharmacology [Biochem Pharmacol] 2025 Feb; Vol. 232, pp. 116723. Date of Electronic Publication: 2024 Dec 17. - Publication Year :
- 2025
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Abstract
- Silent mating-type information regulation 2 homology 3 (SIRT3) is a member of the sirtuins family expressed in mitochondria performs deacetylation of metabolic enzymes and promotes longevity. 7-hydroxy-3-(4'-methoxyphenyl) coumarin (C12) is a small molecule first ever known for its direct activation of SIRT3. SIRT3 performs its function by balancing the redox system by activating manganese superoxide dismutase (MnSOD) and 8-Oxoguanine glycosylase (OGG1). For the first time, we reported that activation of SIRT3 by C12 attenuated bleomycin (BLM)-)-induced acute lung injury and pulmonary fibrosis. C12 prevented the oxidative stress and injury caused by BLM in alveolar epithelial cells (BEAS-2B) in in vitro and inhibited the fibrosis in transforming growth factor-beta (TGF-β) induced fibrosis in fibroblasts (MRC-5). Additionally, activation of SIRT3 by C12 in vivo mice model alleviated BLM-induced inflammation, collagen accumulation, cellular infiltration, and restoration of alveolar architecture by inhibiting TGF-β, smooth muscle actin (α-SMA), collagen-1A, collagen-3A, and mesenchymal markers. The protective effect of C12 was through activation of MnSOD and OGG1 in both in vitro and in vivo models suggesting C12 can be a potent SIRT3 activator and helps to treat fibrotic-related diseases.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Mice
Male
Humans
Cell Line
Oxidative Stress drug effects
Superoxide Dismutase metabolism
DNA Glycosylases metabolism
Bleomycin toxicity
Sirtuin 3 metabolism
Sirtuin 3 genetics
Coumarins pharmacology
Coumarins therapeutic use
Pulmonary Fibrosis chemically induced
Pulmonary Fibrosis drug therapy
Pulmonary Fibrosis metabolism
Pulmonary Fibrosis prevention & control
Pulmonary Fibrosis pathology
Acute Lung Injury chemically induced
Acute Lung Injury drug therapy
Acute Lung Injury metabolism
Acute Lung Injury pathology
Acute Lung Injury prevention & control
Mice, Inbred C57BL
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 232
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 39701544
- Full Text :
- https://doi.org/10.1016/j.bcp.2024.116723