Drug design, development and therapy · 2024
Tomatidine Alleviates Intervertebral Disc Degeneration by Activating the Nrf2/HO-1/GPX4 Signaling Pathway.
СтатьяНазвание и аннотация: Перевод в очереди
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Li Ze, Cheng Pu, Xi Huifeng, Jiang Ting, Zheng Xiaohang, Qiu Jianxin, Gong Yuhang, Wu Xinyu, Mi Shuang, Hong Yuzhen, Hong Zhenghua, Zhou Weiwei
Аннотация
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.
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.