Related Experiment Video
Updated: May 7, 2025
Operational and Intervention Effects of Targeted Tuina in Lumbar Intervertebral Disc Degeneration Model Rabbits
Published on: July 21, 2023
Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway
Ze Li1,2, Pu Cheng1,2, Huifeng Xi1,2
1Department of Orthopaedics, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, People's Republic of China.
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.
