ArticleJournal of cellular and molecular medicine2019
Chalcone flavokawain A attenuates TGF-β1-induced fibrotic pathology via inhibition of ROS/Smad3 signaling pathways and induction of Nrf2/ARE-mediated antioxidant genes in vascular smooth muscle cells.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Medicinal chemistry perspective of chalcone derivatives as anticancer agents: synthetic strategy, biological activity, and structure-activity relationship.Molecular diversity · 2026Review
- Review
- Multi-target therapeutic potential of Flavokawain A in rheumatoid arthritis: A mechanistic and translational perspective.Inflammopharmacology · 2026Review
- Nrf2 signaling in bone health: unlocking new avenues for osteoporosis management.Inflammopharmacology · 2025Review
- Modulating NLRP3 Inflammasomes in Idiopathic Pulmonary Fibrosis: A Comprehensive Review on Flavonoid-Based Interventions.Cell biochemistry and biophysics · 2025Review
- The pharmacological effects and therapeutic potential of flavonoids in digestive diseases.Frontiers in pharmacology · 2025Review
- Effect of garcinol against arsenic-induced neurobehavioral alterations and liver and kidney dysfunction in albino mice.BioMedicine · 2025Article
- The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.International journal of molecular sciences · 2024Review
- Advancements in diabetic foot ulcer research: Focus on mesenchymal stem cells and their exosomes.Heliyon · 2024Review
- Therapeutic Potential of Natural Resources Against Endometriosis: Current Advances and Future Perspectives.Drug design, development and therapy · 2024Review
- Assessment of Oxidative Stress-Induced Oral Epithelial Toxicity.Biomolecules · 2023Article
- High molecular weight hyaluronic acid drastically reduces chemotherapy-induced mucositis and apoptotic cell death.Cell death & disease · 2023Article
- Identification of Novel Cannabinoid CB2 Receptor Agonists from Botanical Compounds and Preliminary Evaluation of Their Anti-Osteoporotic Effects.Molecules (Basel, Switzerland) · 2022Article
- Flavokawain A alleviates the progression of mouse osteoarthritis: AnFrontiers in bioengineering and biotechnology · 2022Article
- Article
- Endogenous SORedox biology · 2021Article
- Mangiferin Inhibits Apoptosis in Doxorubicin-Induced Vascular Endothelial Cells via the Nrf2 Signaling Pathway.International journal of molecular sciences · 2021Article
- The Newly Synthetized Chalcone L1 Is Involved in the Cell Growth Inhibition, Induction of Apoptosis and Suppression of Epithelial-to-Mesenchymal Transition of HeLa Cells.Molecules (Basel, Switzerland) · 2021Article
- Biological Activity, Hepatotoxicity, and Structure-Activity Relationship of Kavalactones and Flavokavins, the Two Main Bioactive Components in Kava (Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Association of NFE2L2 Gene Polymorphisms with Risk and Clinical Characteristics of Acute Type A Aortic Dissection in Han Chinese Population.Oxidative medicine and cellular longevity · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TGF-β1 plays a crucial role in the pathogenesis of vascular fibrotic diseases. Chalcones are reportedly cancer chemo-preventive food components that are rich in fruits and vegetables. In this study, flavokawain A (FKA, 2-30 μM), a naturally occurring chalcone in kava extracts, was evaluated for its anti-fibrotic and antioxidant properties in TGF-β1-stimulated vascular smooth muscle (A7r5) cells, as well as its underlying molecular mechanism of action. Immunofluorescence data showed down-regulated F-actin expression with FKA treatment in TGF-β1-stimulated A7r5 cells. Western blotting demonstrated that FKA treatment suppressed the expression of α-SMA and fibronectin proteins under TGF-β1 stimulation. Findings from wound-healing and invasion experiments showed that FKA inhibits TGF-β1-mediated migration and invasion. Western blotting demonstrated that treatment with FKA down-regulated MMP-9 and MMP-2 and up-regulated TIMP-1 expression. Further evidence showed that FKA decreased TGF-β1-mediated phosphorylation and the transcriptional activity of Smad3. TGF-β1-induced excessive ROS production was remarkably reversed by FKA treatment in A7r5 cells, and inhibition by FKA or N-acetylcysteine (NAC) substantially diminished TGF-β1-induced p-Smad3 activation and wound-healing migration. Interestingly, FKA-mediated antioxidant properties were associated with increased nuclear translocation of Nrf2 and elevated antioxidant response element (ARE) luciferase activity. Activation of Nrf2/ARE signaling was accompanied by the induction of HO-1, NQO-1 and γ-GCLC genes in FKA-treated A7r5 cells. Notably, silencing of Nrf2 (siRNA transfection) significantly diminished the FKA-mediated antioxidant effects, indicating that FKA may inhibit TGF-β1-induced fibrosis through suppressing ROS generation in A7r5 cells. Our results suggested that anti-fibrotic and antioxidant activities of the chalcone flavokawain A may contribute to the development of food-based chemo-preventive drugs for fibrotic diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.