2. Academic Validation
  3. Sakuranetin reduces inflammation and chondrocyte dysfunction in osteoarthritis by inhibiting the PI3K/AKT/NF-κB pathway

Sakuranetin reduces inflammation and chondrocyte dysfunction in osteoarthritis by inhibiting the PI3K/AKT/NF-κB pathway

  • Biomed Pharmacother. 2024 Feb:171:116194. doi: 10.1016/j.biopha.2024.116194.
Xiaofeng Deng 1,  Yunkun Qu 2,  Mengwei Li 3,  Chunyu Wu 4,  Jun Dai 5,  Kang Wei 6,  Haoran Xu 7
Affiliations

Affiliations

  • 1 Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: d202382160@hust.edu.cn.
  • 2 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: m202076278@hust.edu.cn.
  • 3 Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: d202182098@hust.edu.cn.
  • 4 Department of Joint Surgery, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China. Electronic address: jeowcy@smu.edu.cn.
  • 5 Department of Orthopedic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: daijun@suda.edu.cn.
  • 6 Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. Electronic address: weikang@whu.edu.cn.
  • 7 Department of Joint Surgery, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Orthopedics, Academy of Orthopedics·Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China. Electronic address: xuhaoran112194@smu.edu.cn.
PMID: 38262147 DOI: 10.1016/j.biopha.2024.116194
Abstract

Osteoarthritis (OA) is a prevalent degenerative disease that impairs limb function, and its pathogenesis is closely related to inflammation. Sakuranetin (SK) is a cherry flavonoid phytoalexin with potent anti-inflammatory, anti-oxidant, and ant-ifungal properties. In recent studies, flavonoid and phytoalexin-related medicines have shown promise in the treatment of OA. However, the effects of SK on chondrocyte inflammation and the chondrogenesis process have remained unexplored, as have its functions in OA treatment. This study sought to confirm the therapeutic effects of SK in the OA rat model and reveal the potential mechanisms for protecting chondrocytes. The relevant mechanisms of SK were analyzed by network pharmacology analysis. Chondrocytes were subjected to IL-1β intervention to simulate an inflammatory environment and received SK treatment. Then, anabolism, catabolism, and inflammatory markers were detected by western blot, qPCR, elisa, and immunofluorescence. Chondrogenic ability was evaluated by micromass and 3D culture assays. The rats were treated with destabilization of the medial meniscus (DMM) surgery to establish an OA model and SK intra-articular injections subsequently. Histological staining, immunohistochemistry, and micro-CT were performed to analyze the structural and morphological changes of cartilage and subchondral bone. In chondrocytes, IL-1β treatment reduced chondrogenic ability, promoted catabolism, and exacerbated inflammation by triggering the PI3K/Akt/NF-κB pathway, whereas SK treatment partially rescued these negative effects. In vivo, SK treatment effectively alleviated the degeneration of cartilage and subchondral bone, thereby delaying the progression of OA. In summary, SK alleviates chondrocyte inflammation and promotes chondrogenesis by inhibiting the PI3K/Akt/NF-κB pathway, thereby improving OA progression.

Keywords

Chondrocyte; Chondrogenesis; Inflammation; Osteoarthritis; Sakuranetin.

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