Abstract
Osteoarthritis (OA) is a prevalent joint degenerative disease involving inflammation and oxidative stress, with reactive oxygen species (ROS) driving progression. Restoring joint redox balance mitigates cartilage damage. Osilyhizidine (OSR), from Sophora alopecuroides, has anti-inflammatory/antioxidant properties, but its OA-specific effects and mechanisms were unclear. In vitro experiments assessed OSR’s impact on OA chondrocyte proliferation, repair, and inflammation, focusing on Glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) regulation. A murine OA model validated findings in vivo. OSR showed anti-inflammatory, antioxidant effects and promoted cartilage repair, enhancing chondrocyte functions under inflammation and suppressing pro-inflammation. It upregulated GPX4 (improving ROS detoxification) and SLC7A11 (facilitating glutathione synthesis for redox balance) at transcriptional and protein levels. These were confirmed in mice. OSR alleviates OA by activating GPX4/SLC7A11 to regulate ROS and oxidative stress, emerging as a promising OA therapeutic candidate, offering insights into redox-targeted interventions.
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Data availability
All data generated or analyzed during this study are available from the corresponding author upon reasonable request. The datasets include raw Western blot images, RT-qPCR Ct values, flow cytometry files, histological and immunohistochemical images, and molecular docking results. All data have been carefully validated, and the authors affirm their accuracy and reliability. Requests for access should be directed to the corresponding author.
Abbreviations
- CETSA:
-
Cellular thermal shift assay
- COX‑2:
-
Cyclooxygenase‑2
- DMSO:
-
Dimethyl sulfoxide
- GPX4:
-
Glutathione peroxidase 4
- GSH:
-
Glutathione
- H&E:
-
Hematoxylin and eosin
- IL‑6:
-
Interleukin‑6
- MDA:
-
Malondialdehyde
- MMP‑13:
-
Matrix metallopeptidase 13
- OA:
-
Osteoarthritis
- OSR:
-
Oxysophoridine
- ROS:
-
Reactive oxygen species
- SLC7A11:
-
Solute carrier family 7 member 11
- TNF‑α:
-
Tumor necrosis factor‑α
- 4‑HNE:
-
4‑Hydroxynonenal
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Acknowledgements
The authors gratefully acknowledge financial support from the Health Research Program of Anhui Province (Grant No. AHWJ2024Aa20135).
Funding
This work was supported by the Health Research Program of Anhui (Grant No. AHWJ2024Aa20135).
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Jun Tu (First Author): Conceptualization, Methodology, Software, Investigation, Formal Analysis, Writing—Original Draft, Writing—Review & Editing; Zhiwei Peng: Data Curation, Writing—Original Draft, Writing—Review & Editing; Haobo Liu: Visualization, Investigation, Writing—Review & Editing; Xiyang Sun :Visualization, Writing—Review & Editing; Jianqi Zhao: Resources, Supervision, Writing—Review & Editing; Bin Xu: Software, Validation, Writing—Review & Editing; XuZhu: Concepualization,Methodology, Writing—review Editing. Baofang Liu:(Corresponding Author): Conceptualization, Funding Acquisition, Resources, Supervision, Writing—Review Editing. All authors agreed on the journal for submission, reviewed and approved all versions of the manuscript, and accept responsibility for the published content.
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Tu, J., Peng, Z., Sun, X. et al. Oxysophoridine promotes osteoarthritis repair via GSH system activation and ROS suppression. Sci Rep (2026). https://doi.org/10.1038/s41598-026-37912-1
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DOI: https://doi.org/10.1038/s41598-026-37912-1
