2. Academic Validation
  3. Vaccarin ameliorates osteoarthritis by suppressing the c-Jun N-terminal kinase (JNK)-serum amyloid A2 (SAA2) pathway mediating chondrocyte senescence

Vaccarin ameliorates osteoarthritis by suppressing the c-Jun N-terminal kinase (JNK)-serum amyloid A2 (SAA2) pathway mediating chondrocyte senescence

  • Phytomedicine. 2025 Jun:141:156697. doi: 10.1016/j.phymed.2025.156697.
Xin Gan 1,  Jianwen Li 1,  Yongqiao Jiang 1,  Xiaohui Wang 2,  Yunqian Zeng 1,  Xin Chen 1,  Hui Huang 1,  Juan Min 3,  Guanghao Li 4,  Mingbo Nie 5,  Hao Kang 6
Affiliations

Affiliations

  • 1 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
  • 2 The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
  • 3 Institutional Center for Shared Technologies and Facilities of Wuhan, Institute of Virology, Chinese Academy of Sciences, Wuhan 430010, PR China.
  • 4 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: [email protected].
  • 5 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: [email protected].
  • 6 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. Electronic address: [email protected].
PMID: 40215820 DOI: 10.1016/j.phymed.2025.156697
Abstract

Background: Osteoarthritis is a chronic degenerative joint disease marked by chondrocyte senescence and extracellular matrix degradation. Vaccarin, a flavonoid with anti-inflammatory and antioxidant properties, has not been previously investigated for its therapeutic potential in osteoarthritis.

Purpose: To evaluate the therapeutic potential of Vaccarin in osteoarthritis and elucidate its underlying mechanisms.

Design and method: This study utilized in vitro chondrocyte cultures and RNA Sequencing to identify relevant pathways, followed by validation at the genetic, protein, and metabolic levels using multiple approaches. Additionally, the therapeutic effects of Vaccarin were assessed in vivo using a destabilization of the medial meniscus (DMM)-induced osteoarthritis mouse model and human cartilage samples from osteoarthritis patients.

Results: Vaccarin effectively ameliorated osteoarthritis both in vivo and in vitro. Transcriptomic Sequencing indicated a significant downregulation of serum amyloid A2 (SAA2) expression following Vaccarin treatment. Multi-omics analysis, validated by human specimens, indicated that SAA2 is minimally secreted in healthy articular cartilage but serves as a crucial osteoarthritis biomarker in Asian populations. Mechanistically, Vaccarin inhibits c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing SAA2 expression and mitigating chondrocyte inflammation and senescence. Notably, inflammatory conditions upregulate SAA2 expression in chondrocytes via the JNK pathway. Elevated SAA2 levels contribute to mitochondrial dysfunction in chondrocytes, leading to increased Reactive Oxygen Species (ROS) production and exacerbating osteoarthritis progression.

Conclusion: This study identifies SAA2 as a potential therapeutic target for osteoarthritis and suggests that Vaccarin presents a promising treatment avenue.

Keywords

JNK; Osteoarthritis; ROS; SAA2; Senescence; Vaccarin.

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