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

Yifeng Shi; Jiaoxiang Chen; Sunlong Li; Yuhao Wu; Caiyu Yu; LiBin Ni; Jian Xiao; Zhenxuan Shao; Huanqing Zhu; Jianshun Wang; Xiangyang Wang; Xiaolei Zhang

doi:10.1016/j.phymed.2022.153928

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. Epub 2022 Jan 5.

Authors

Yifeng Shi¹, Jiaoxiang Chen¹, Sunlong Li¹, Yuhao Wu², Caiyu Yu³, LiBin Ni¹, Jian Xiao¹, Zhenxuan Shao¹, Huanqing Zhu², Jianshun Wang¹, Xiangyang Wang⁴, Xiaolei Zhang⁵

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.