ArticleCell death & disease2019
Flavones hydroxylated at 5, 7, 3' and 4' ameliorate skin fibrosis via inhibiting activin receptor-like kinase 5 kinase activity.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Protecting kidney function: from mechanisms to therapeutic targets and traditional Chinese medicine.Renal failure · 2025Review
- Quercetin, Kaempferol and Capsaicin Counteract the TGF-β1-Induced Upregulation of αSMA and Collagen in Myoblasts.International journal of molecular sciences · 2025Article
- Innovative Nanocomposites for Drug Delivery: A Novel Approach for Diabetic Foot Ulcer.Current drug delivery · 2025Review
- Luteolin for the Treatment of Organ Fibrosis: A Mini Review.Mini reviews in medicinal chemistry · 2025Review
- The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.European respiratory review : an official journal of the European Respiratory Society · 2025Review
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- Salvianolic Acid B Attenuates Hypertrophic Scar Formation In Vivo and In Vitro.Aesthetic plastic surgery · 2023Article
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- Laricitrin 3-Rutinoside fromAntioxidants (Basel, Switzerland) · 2023Article
- Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models.Scientific reports · 2022Article
- Inhibitory Effects of 3',4'-Dihydroxyflavonol in a Mouse Model of Glaucoma Filtration Surgery and TGFβ1-Induced Responses in Human Tenon's Fibroblasts.Translational vision science & technology · 2022Article
- The Molecular Mechanism of Polyphenols with Anti-Aging Activity in Aged Human Dermal Fibroblasts.Molecules (Basel, Switzerland) · 2022Review
- The potential of functionalized dressing releasing flavonoids facilitates scar-free healing.Frontiers in medicine · 2022Review
- Curcumin and its nano-formulations: Defining triple-negative breast cancer targets through network pharmacology, molecular docking, and experimental verification.Frontiers in pharmacology · 2022Article
- Molecular Mechanisms of Luteolin Against Atopic Dermatitis Based on Network Pharmacology and in vivo Experimental Validation.Drug design, development and therapy · 2022Article
- Regulatory Effects of Quercetin on M1/M2 Macrophage Polarization and Oxidative/Antioxidative Balance.Nutrients · 2021Article
- Article
- Kaempferol attenuates liver fibrosis by inhibiting activin receptor-like kinase 5.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Skin fibrosis is mainly characterized by excessive collagen deposition. Studies have recently identified a number of flavonoids with variable structures that have the potency of inhibiting collagen synthesis and thus attenuating organ fibrosis. In this study, we found that flavones with 5, 7, 3', 4' hydroxy substitution reduced collagen expression most efficiently. Among those flavones, luteolin, quercetin, and myricetin were selected for follow-up. In vivo, the three compounds ameliorated skin fibrosis and reduced collagen deposition. Further analysis showed the compounds had significant inhibition on the proliferation, activation and contractile ability of dermal fibroblasts in vitro and in vivo. More importantly, we revealed that luteolin, quercetin, and myricetin selectively downregulated the phosphorylation of Smad2/3 in TGF-β/Smads signaling via binding to activin receptor-like kinase 5 (ALK5) and impairing its catalytic activity. We also found flavones with 5, 7, 3', 4' hydroxy substitution showed stronger affinity with ALK5 compared with other flavonoids. Herein, we identified at least in part the underlying molecular basis as well as the critical structures that contribute to the antifibrotic bioactivity of flavones, which might benefit drug design and modification.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.