2. Academic Validation
  3. Cynarin alleviates intervertebral disc degeneration via protecting nucleus pulposus cells from ferroptosis

Cynarin alleviates intervertebral disc degeneration via protecting nucleus pulposus cells from ferroptosis

  • Biomed Pharmacother. 2023 Sep:165:115252. doi: 10.1016/j.biopha.2023.115252.
Pu Zhang 1,  Kewei Rong 1,  Jiadong Guo 1,  Lei Cui 2,  Keyu Kong 1,  Chen Zhao 1,  Huan Yang 3,  Hongtao Xu 4,  An Qin 1,  Peixiang Ma 5,  Xiao Yang 6,  Jie Zhao 7
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
  • 2 Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning 530000, China.
  • 3 The Second Clinical Medical College of Yunnan University of Traditional Chinese Medicine, Kunming 650500, China.
  • 4 Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
  • 5 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: mapx@shsmu.edu.cn.
  • 6 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: walkingweapon@outlook.com.
  • 7 Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: profzhaojie@126.com.
PMID: 37536034 DOI: 10.1016/j.biopha.2023.115252
Abstract

Intervertebral disc degeneration (IVDD) leads to a series of degenerative spine diseases. Clinical treatment of IVDD is mainly surgery, lacking effective drugs to alleviate intervertebral disc degeneration. In this study, we analysed the mRNA Sequencing dataset of human degenerative intervertebral disc tissues and revealed the participation of Ferroptosis in IVDD. Furthermore, we confirmed that TNF-α, an important cytokine in IVDD, induces Ferroptosis in nucleus pulposus cells. Subsequently, a Ferroptosis inhibitors screening strategy using multiple Ferroptosis indicators was developed. Through the screen of various natural compounds, cynarin, a natural product enriched in Artichoke, was discovered to inhibit Ferroptosis of nucleus pulposus cells. Cynarin can dose-dependently inhibit the catabolism of nucleus pulposus cells, increase the expression of key ferroptosis-inhibiting genes (GPX4 and NRF2), inhibit the increment of cellular Fe2+, lipid peroxides, and Reactive Oxygen Species. It can also prevent mitochondria shrinkage, reduce mitochondria cristae density in Ferroptosis, and prevent IVDD in the rat model. In conclusion, cynarin is a potential candidate for the drug development for IVDD.

Keywords

Cynarin; Drug discovery; Ferroptosis; Intervertebral disc degeneration; TNF-α.

Figures
Products