An intricate role of Ang II/AT1 in the modulation of monosodium glutamate-induced pulmonary fibrosis by TGF-β/Smad through quercetin
Abstract To investigate the protective actions of the natural flavonoid quercetin against monosodium glutamate (MSG)-induced pulmonary fibrosis in rats, the present study targets the modulation of the TGF-β/Smad signaling pathway and the involvement of Ang II/AT1. The experimental model involved the...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-05781-9 |
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| Summary: | Abstract To investigate the protective actions of the natural flavonoid quercetin against monosodium glutamate (MSG)-induced pulmonary fibrosis in rats, the present study targets the modulation of the TGF-β/Smad signaling pathway and the involvement of Ang II/AT1. The experimental model involved the treatment of rats with MSG (0.6 g/kg body weight) for 4 weeks and quercetin dosages of 25 mg, 50 mg, and 100 mg/kg body weight. The study applied the combination of biochemical, molecular, and histopathological evaluation to identify the role of quercetin in impacting major cytokines (IL-17, IL-19, TGF-β, VEGF), oxidative stress markers (TBARS, NO, SOD, CAT, GSH), extracellular matrix components (collagen-I, α-SMA, fibronectin), and fibrosis gene expression (TGF-β1, Smad2/3/4, CTGF, Snail, Slug). MSG treatment increased pro-fibrotic cytokines, oxidative stress, and deposition of collagen in a significant amount, while administration of quercetin dose-dependently reversed the alterations. Quercetin also reversed the activity of antioxidant enzymes, reduced inflammatory cytokines, and inhibited TGF-β/Smad signaling as indicated by lowered TGF-β receptor II activation and following Smad phosphorylation. Molecular docking demonstrated that quercetin competitively binds to TGF-β receptor II to inhibit MSG-induced fibrotic signaling. Quercetin inhibits MSG-induced lung fibrosis by inhibiting collagen accumulation and inflammatory cell invasion and has the potential to produce therapeutic effects by modulating TGF-β/Smad signaling and restoring lung tissue homeostasis. |
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| ISSN: | 2045-2322 |