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Tetrandrine Represses Inflammation and Attenuates Osteoarthritis by Selective Inhibition of COX-2

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Abstract

Objective

There is a lack of effective and long-term safe drugs for the treatment of osteoarthritis (OA). Tetrandrine (Tet) has been approved and used to treat rheumatoid arthritis for several decades, but its effect on OA has not been investigated. Herein, we explored the effect of Tet on OA and its underlying mechanism.

Methods

OA was induced using destabilization of the medial meniscus (DMM) in C57BL/6J mice. The animals were randomly divided into sham, DMM, Tet, celecoxib (CXB), and indomethacin (INDO) groups. Each group was given solvent or corresponding drugs by gavage for 7 weeks after convalescence. Pathological staining, OARSI scores, micro-computed tomography and behavior tests were performed to evaluate the effects of Tet.

Results

Tet remarkably alleviated cartilage injury in the knee joint, limited bone remodeling in the subchondral bone, and delayed progression of OA. Tet also significantly relieved joint pain and maintained function. Further mechanistic studies revealed that Tet lowered inflammatory cytokine levels and selectively suppressed gene and protein expression of cyclooxygenase (COX)-2 but not COX-1 (P<0.01). Tet also reduced the production of prostaglandin E2 without damaging the gastric mucosa.

Conclusion

We found that Tet could selectively inhibit COX-2 gene expression and decrease cytokine levels in mice, thus reducing inflammation and improving OA without obvious gastric adverse events. These results provide a scientific basis for the clinical application of Tet in the treatment of OA.

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Author notes

  1. The authors contributed equally to this study.

Authors and Affiliations

  1. Department of Pharmacy, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430016, China

    Ping Gao

  2. Department of Pharmacy, Central Hospital of Xianning, the First Affiliate Hospital of Hubei University of Science and Technology, Xianning, 437100, China

    Zhi-wei Rao

  3. Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Min Li, Qian-yan Gao, Tian-ze Shang & Cheng-liang Zhang

  4. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Xu-ying Sun & Chao Chen

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  1. Ping Gao
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Corresponding authors

Correspondence to Chao Chen or Cheng-liang Zhang.

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Conflict of Interest Statement

The authors declare that there is no conflict of interest with any financial organization or corporation or individual that can inappropriately influence this work.

This study was supported by the Natural Science Foundation of Hubei Province (No. 2020CFB868).

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Gao, P., Rao, Zw., Li, M. et al. Tetrandrine Represses Inflammation and Attenuates Osteoarthritis by Selective Inhibition of COX-2. CURR MED SCI 43, 505–513 (2023). https://doi.org/10.1007/s11596-023-2725-6

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  • DOI: https://doi.org/10.1007/s11596-023-2725-6

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