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Myricetin Protects Against Rat Intervertebral Disc Degeneration Partly Through the Nrf2/HO-1/NF-κB Signaling Pathway

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Abstract

Intervertebral disc (IVD) degeneration (IDD) is a prevalent musculoskeletal disorder. Nucleus pulposus cells (NPCs) play a significant role in the normal functioning of the IVD. Myricetin is an agent that exerts anti-inflammatory and antioxidant effects in various pathological conditions. Here, we investigated the ameliorative effects of myricetin on the IVD degeneration. NPCs were obtained from the IVD of rats, and were treated with myricetin (0, 5, 10, 15, 20 μM) for 24 h before 20 ng/mL IL-1β stimulation. RT-qPCR, western blotting, and ELISA were applied to evaluate the levels of inflammatory factors (iNOS, COX-2, TNF-α, IL-6, PGE2, and Nitrite) and extracellular matrix (ECM)-associated components (MMP13, ADAMTS-5, aggrecan, and collagen II) in NPCs. Activation status of related signaling pathways (NF-κB and Nrf2) was determined using western blotting and immunofluorescence staining. Experimental rat models of IDD were established using a needle puncture method. Myricetin (20 mg/kg) was administrated intraperitoneally, and the degeneration was evaluated using histopathological analysis. Myricetin treatment attenuated the IL-1β-induced production of inflammatory factors in NPCs. Downregulation of aggrecan and collagen II as well as upregulation of MMP-13 and ADAMTS-5 in NPCs caused by IL-1β was reversed by myricetin treatment. Mechanistically, myricetin blocked NF-κB signaling by activation of Nrf2 in IL-1β-stimulated NPCs. Moreover, inhibition of Nrf2 reversed the protective effects of myricetin in NPCs. The in vivo experiments showed that myricetin ameliorated the IDD progression in rats. The present work suggests that Nrf2 is involved in the pathogenesis of IDD and shows the protective effects as well as the underlying mechanism of myricetin on Nrf2 activation in NPCs.

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Data Availability

The data used to support the findings of this study are included within the article.

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Acknowledgements

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Funding

The work was supported by Effects of Anxiety and Depression on Rehabilitation in Patients with Lumbar Spinal Stenosis After Open Surgery and Its Mechanism (Approval Number: WJ2021F121) and Clinical Study on The Treatment of Abdominal Distension After Thoracolumbar Fractures with Jiawei Taohe Chengqi Combined with Umbilical Paste (Approval Number: ZY2021F016).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, Hubei, China

    Tian Mao

  2. Department of Orthopedics Ward 1, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, No. 11, Lingjiaohu Road, Jianghan District, Wuhan, 430015, Hubei, China

    Junchi Fan

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  1. Tian Mao
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Contributions

TM conceived and designed the experiments, TM and JF carried out the experiments. TM and JF analyzed the data. TM and JF drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.

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Correspondence to Junchi Fan.

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The authors declare no conflict of interest.

Ethical Approval

All animal experiments were approved by the Ethics Committee of Wuhan Myhalic Biotechnology Co., Ltd (Approval Number: HLK-20211206173) and were performed following the NIH Guide for the Care and Use of Laboratory Animals.

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Mao, T., Fan, J. Myricetin Protects Against Rat Intervertebral Disc Degeneration Partly Through the Nrf2/HO-1/NF-κB Signaling Pathway. Biochem Genet 62, 950–967 (2024). https://doi.org/10.1007/s10528-023-10456-z

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  • DOI: https://doi.org/10.1007/s10528-023-10456-z

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