Tangeretin suppresses osteoarthritis progression via the Nrf2/NF-κB and MAPK/NF-κB signaling pathways

  • Phytomedicine. 2022 Apr:98:153928. doi: 10.1016/j.phymed.2022.153928.
Yifeng Shi  1 ,  Jiaoxiang Chen  1 ,  Sunlong Li  1 ,  Yuhao Wu  2 ,  Caiyu Yu  3 ,  LiBin Ni  1 ,  Jian Xiao  1 ,  Zhenxuan Shao  1 ,  Huanqing Zhu  2 ,  Jianshun Wang  1 ,  Xiangyang Wang  4 ,  Xiaolei Zhang  5
Affiliations
  • 1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 2. The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 3. School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
  • 4. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: [email protected].
  • 5. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. Electronic address: [email protected].
PMID: 35104760 DOI: 10.1016/j.phymed.2022.153928
Abstract

Background: Osteoarthritis (OA) is a globally prevalent degenerative disease characterized by extracellular matrix (ECM) degradation and inflammation. Tangeretin is a natural flavonoid that has anti-inflammatory properties. Studies have not explored whether tangeretin modulates OA development.

Purpose: The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of tangeretin.

Study design: Effects of tangeretin on OA were detected in chondrocytes and OA mouse model.

Methods: Protective effects of tangeretin on murine articular chondrocytes treated with interleukin-1β (IL-1β) were evaluated using qPCR, western blot analysis, ELISA, ROS detection and immunofluorescent staining in vitro. Healing effect of tangeretin on cartilage degradation in mice was assessed through X-ray imaging, histopathological analysis, immunohistochemical staining and immunofluorescent staining in vivo.

Results: Tangeretin suppressed IL-1β-mediated inflammatory mediator secretion and degradation of ECM in chondrocytes. The results showed that tangeretin abrogated destabilized medial meniscus (DMM)-induced cartilage degradation in mice. Mechanistic studies showed that tangeretin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and suppressing MAPK signaling pathway.

Conclusion: Tangeretin abrogates OA progression by inhibiting inflammation as well as ECM degradation in chondrocytes and animal models. Effects of tangeretin are mediated through Nrf2/NF-κB and the MAPK/NF-κB pathways. Thus, tangeretin is a potential therapeutic agent for osteoarthritis treatment.

Keywords
Inflammation; MAPK; NF-κB; Nrf2; Osteoarthritis; Tangeretin.
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