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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.

Authors :
Devabattula G
Bakchi B
Sharma A
Panda B
Madhavi V
Godugu C
Source :
Biochemical pharmacology [Biochem Pharmacol] 2025 Feb; Vol. 232, pp. 116723. Date of Electronic Publication: 2024 Dec 17.
Publication Year :
2025

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.)

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