ArticleFrontiers in pharmacology2025
Paeonol ameliorates ferroptosis and inflammation in chondrocytes through AMPK/Nrf2/GPX4 pathway.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Paeonol Alleviate Cisplatin- and Noise-Induced Hearing Loss by Preserving Hair Cell Ribosome Biogenesis.CNS neuroscience & therapeutics · 2026Article
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Paeonol attenuates atherosclerosis by inhibiting mTORJournal of translational internal medicine · 2026Article
- Paeoniflorin's role in inhibiting malignant metastasis of gastrointestinal stromal tumors via CYP3A4 modulation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A dual-pronged strategy: multi-bioactive nanoplatform synergizes ROS antidote and iron stabilization to protect against liver ischemia-reperfusion injury.Journal of nanobiotechnology · 2026Article
- Genetic Diagnosis and Identification of a Novel De Novo RELA Variant in Familial Behçet-like Autoinflammatory Syndrome Type 3: A Case Report.Journal of clinical immunology · 2026Article
- Targeting Ferroptosis With Natural Products for the Treatment of Skeletal System Disease: An Updated Review.Journal of cellular and molecular medicine · 2026Review
- CXCL12 Promotes Peripheral Nerve Injury Repair by Inhibiting the Ferroptosis-Inflammation Axis via the ERK/Nrf2 Pathway.Inflammation · 2026Article
- Kaempferol Attenuates Oxidative Stress-Induced Injury in Gastric Mucosal Cells by Activating Nrf2/GPX4 Axis to Inhibit Ferroptosis.Immunity, inflammation and disease · 2026Article
- Paeonol protects against cisplatin-induced premature ovarian failure via anti-inflammatory and antioxidant activities: an integrated approach of network pharmacology, molecular dynamics simulation, and experimental validation.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The Nrf2/HO-1 signaling pathway in arthritis: from molecular mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Ferroptosis in osteoarthritis: metabolic reprogramming, immunometabolic crosstalk, and targeted intervention strategies.Frontiers in immunology · 2025Review
- Glutathione peroxidase 4 as an emerging therapeutic target in osteoarthritis: focus on ferroptosis.Frontiers in cell and developmental biology · 2025Review
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Introduction: Chondrocyte ferroptosis is an important component of the pathogenesis of osteoarthritis. Paeonol, the main pharmacologically active ingredient of the Paeonia suffruticosa Andrews, is a natural radical scavenger with potent biological activities, including antioxidant, anti-inflammatory, and cartilage protection effects. However, the molecular mechanisms underlying its role in regulating chondrocytes ferroptosis remain unclear. Methods: To investigate the effect of paeonol on ferroptosis and inflammation of chondrocytes through interleukin-1β (IL-1β), the proliferation activity, lipid peroxidation level, endogenous antioxidant capacity, and mitochondrial membrane potential of chondrocytes were evaluated in detail. Intracellular ferrous ion concentration was detected by FerroOrange fluorescent probe staining. Western blotting and immunofluorescence staining were used to detect biomarker proteins of ferroptosis, inflammation, and AMPK/Nrf2/GPX4 signaling pathway proteins. Results: The results showed that paeonol significantly depressed IL-1β-induced ferroptosis and inflammation in chondrocytes. Specifically, paeonol protects cell viability, reduces lipid peroxidation damage, maintains mitochondrial function, and inhibits pro-ferroptosis and pro-inflammation biomarker proteins. In addition, the anti-inflammatory ability of paeonol was partially inhibited after the addition of ferroptosis agonist erastin, suggesting that paeonol protects against inflammatory injury in part by inhibiting ferroptosis. Further studies showed that paeonol activated AMPK phosphorylation and promoted Nrf2 nuclear translocation and Keap1 degradation. Finally, the AMPK-Nrf2-GPX4 signaling pathway was confirmed to be the underlying mechanism of paeonol against ferroptosis by the simultaneous use of the AMPK agonist and Nrf2 inhibitor. Conclusion: These results indicate that paeonol significantly inhibits IL-1β-induced ferroptosis and inflammation in chondrocytes, and the underlying mechanism of paeonol against ferroptosis is partly through the AMPK/Nrf2/GPX4 axis.
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