2. Academic Validation
  3. Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway

Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway

  • Drug Des Devel Ther. 2024 Dec 27:18:6313-6329. doi: 10.2147/DDDT.S481714.
Ze Li # 1 2,  Pu Cheng # 1 2,  Huifeng Xi # 1 2,  Ting Jiang 1 2,  Xiaohang Zheng 1 2,  Jianxin Qiu 1 2,  Yuhang Gong 1 2,  Xinyu Wu 1 2,  Shuang Mi 1 2,  Yuzhen Hong 3,  Zhenghua Hong 1 2,  Weiwei Zhou 1 2
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, People's Republic of China.
  • 2 Bone Development and Metabolism Research Center of Taizhou Hospital, Linhai, Zhejiang Province, People's Republic of China.
  • 3 School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province, 430065, People's Republic of China.
  • # Contributed equally.
PMID: 39741916 DOI: 10.2147/DDDT.S481714
Abstract

Purpose: Intervertebral disc degeneration (IDD) is a leading cause of low back pain, and developing new molecular drugs and targets for IDD is a new direction for future treatment strategies. The aim of this study is to investigate the effects and mechanisms of tomatidine in ameliorating lumbar IDD.

Methods: Nucleus pulposus cells (NPCs) exposed to lipopolysaccharides were used as an in vitro model to investigate changes in the expression of extracellular matrix components and associated signaling pathway molecules. A lumbar instability model was used to simulate IDD. Tomatidine (Td) was then administered intraperitoneally, and its effects were evaluated through histopathological analysis.

Results: In vitro, Td significantly promoted ECM anabolism, inhibited ECM catabolism, and reduced oxidative stress and Ferroptosis in LPS-stimulated NPCs. When Nrf2 expression was inhibited, oxidative stress and Ferroptosis were exacerbated, and the protective effects of Td on NPCs were lost, suggesting the Nrf2/HO-1/GPX4 axis is critical for the therapeutic effects of Td. In vivo, histopathological analysis demonstrated that Td ameliorated IDD in a murine model.

Conclusion: Td alleviates IDD in vitro and in vivo by activating the Nrf2/HO-1/GPX4 pathway to inhibit Ferroptosis in NPCs. This mechanism suggests Td is a promising candidate for IDD treatment.

Keywords

GPX4; Nrf 2; ferroptosis; intervertebral disc degeneration; tomatidine.

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