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Evodiamine ameliorates intervertebral disc degeneration through the Nrf2 and MAPK pathways

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Abstract

Degradation of extracellular matrix (ECM), reactive oxygen species (ROS) production, and inflammation are critical players in the pathogenesis of intervertebral disc degeneration (IDD). Evodiamine exerts functions in inhibiting inflammation and maintaining mitochondrial antioxidant functions. However, the biological functions of evodiamine and its related mechanisms in IDD progression remain unknown. The IDD-like conditions in vivo were stimulated via needle puncture. Hematoxylin and eosin staining, Safranin O/Fast Green staining and Alcian staining were performed to determine the degenerative status. The primary nucleus pulposus cells (NPCs) were isolated from Sprague–Dawley rats and then treated with tert-butyl peroxide (TBHP) to induce cellular senescence and oxidative stress. The cell viability was assessed by cell counting kit-8 assays. The mitochondria-derived ROS in NPCs was evaluated by MitoSOX staining. The mitochondrial membrane potential in NPCs was identified by JC-1 staining and flow cytometry. The expression of collagen II in NPCs was measured by immunofluorescence staining. The levels of mRNAs and proteins were measured by RT-qPCR and western blotting. The Nrf2 expression in rat nucleus pulposus tissues was measured by immunohistochemistry staining. Evodiamine alleviated TBHP-induced mitochondrial dysfunctions in NPCs. The enhancing effect of TBHP on the ECM degradation was reversed by evodiamine. The TBHP-stimulated inflammatory response was ameliorated by evodiamine. Evodiamine alleviated the IDD process in the puncture-induced rat model. Evodiamine promoted the activation of Nrf2 pathway and inactivated the MAPK pathway in NPCs. In conclusion, evodiamine ameliorates the progression of IDD by inhibiting mitochondrial dysfunctions, ECM degradation and inflammation via the Nrf2/HO-1 and MAPK pathways.

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Acknowledgements

We appreciate the support from the Wuhan Hospital of Traditional Chinese Medicine.

Funding

This work was supported by Wuhan Municipal Health Commission (approval number: WZ15B09).

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Author notes

  1. Tian Xie and Xi Gu have contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, Wuhan Hospital of Traditional Chinese Medicine, No. 49 Lihuangpi Road, Jiang’an District, Wuhan, 430014, China

    Tian Xie & Xi Gu

  2. College of Acupuncture and Bone Injury, Hubei University of Chinese Medicine, Wuhan, 430061, China

    Ruijie Pan, Wenzhuo Huang & Sheng Dong

Authors
  1. Tian Xie
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  2. Xi Gu
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  3. Ruijie Pan
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  4. Wenzhuo Huang
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  5. Sheng Dong
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Contributions

XG and TX were the main designers of this study. XG, TX, RP, WH, SD performed the experiments and analyzed the data. XG and TX drafted the manuscript. All authors read and approved the final manuscript.

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Correspondence to Tian Xie.

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The authors have not disclosed any conflict of interests.

Ethical approval

The experimental protocols were granted approval from the Ethics Committee of Wuhan Myhalic Biotechnology Co., Ltd (No. 202007109) and abided by the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Xie, T., Gu, X., Pan, R. et al. Evodiamine ameliorates intervertebral disc degeneration through the Nrf2 and MAPK pathways. Cytotechnology 76, 153–166 (2024). https://doi.org/10.1007/s10616-023-00605-y

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