Hesperidin mitigates oxidative stress-induced ferroptosis in nucleus pulposus cells via Nrf2/NF-κB axis to protect intervertebral disc from degeneration

Zhu, Jian; Sun, Ruping; Chang, Yan; Sun, Kaiqiang; Gao, Lu; Zheng, Bing; Shi, Jiangang

doi:10.1080/15384101.2023.2200291

Cited by 14 publications

(3 citation statements)

References 64 publications

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“…It also shows potential in mitigating ferroptosis induced by silver nanoparticles in human bronchial epithelial BEAS-2B cells through the Nrf2/HO-1 axis ( Zhang et al, 2022b ). Hesperidin and naringin have both been found to inhibit ferroptosis by upregulating the Nrf2 pathway, offering protection to human myeloid cells ( Tang et al, 2022 ; Zhu et al, 2023 ).…”

Section: Small Molecule Ferroptosis Inhibitorsmentioning

confidence: 99%

Ferroptosis inhibitors: past, present and future

Zhang,

Luo,

Xiang

et al. 2024

Front. Pharmacol.

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Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.

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Section: Small Molecule Ferroptosis Inhibitorsmentioning

confidence: 99%

Ferroptosis inhibitors: past, present and future

Zhang,

Luo,

Xiang

et al. 2024

Front. Pharmacol.

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“… 97 Recently, Zhu et al confirmed that HRD may protect NP cells from degeneration by mitigating oxidative stress-dependent ferroptosis via enhancing the expression of Nrf2 and suppressing NF-κB pathway. 98 Astaxanthin (Ast), a natural lipid-soluble carotenoid, possesses antioxidant, anti-inflammatory, and anti-aging capacities. Additional supplement with Ast could protect vertebral cartilage endplate degeneration against TBHP-induced cartilage endplate chondrocytes ferroptosis including restoring the downregulated expression of GPX4, ferritin heavy chain (FTH1) and solute carrier family 7 member 11 (SLC7A11) via activating Nrf-2/HO-1 pathway.…”

Section: Therapeutic Strategies By Targeting Nrf2mentioning

confidence: 99%

The Pivotal Role of Nrf2 Signal Axis in Intervertebral Disc Degeneration

Pan,

Hou,

Deng

et al. 2023

JIR

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Intervertebral disc degeneration (IDD) is considered as a dominant contributor to low back pain (LBP), causing severe pain, limited range of lumbar motion, physical dysfunction, and restriction of social activity. However, the specific pathological mechanisms underlying IDD remain elusive, and effective strategies to delay the pathogenesis of IDD are still unclear and limited. In recent years, some studies have found that nuclear factor erythroid 2-related factor 2 (Nrf2), an important antioxidant transcription factor, may play crucial roles in the pathogenesis and progression of age-related diseases including IDD. Nrf2 can maintain redox homeostasis and protecting nucleus pulposus (NP) cells against oxidative stress, inflammatory response, extracellular matrix (ECM) catabolism, cell senescence and cell death involving in the progression of IDD. In this review, we aim to systematically describe the vital roles and pathological mechanism of Nrf2 signaling axis in the pathogenesis of IDD, which may put forward potential therapeutic strategies for the prevention and treatment of IDD by targeting Nrf2.

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“…The nuclear factor-kappa B (NF-κB) signaling pathway is implicated in the regulation of inflammation, cell proliferation, and ECM homeostasis in the intervertebral disc 24 , 25 . Dysregulation of the NF-κB pathway has been associated with the severity of IVDD, as reflected by increased ECM degradation, reduced disc cell viability, and enhanced inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis

Sun,

Zhu,

Sun

et al. 2023

Int. J. Med. Sci.

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Intervertebral disc degeneration (IVDD) is a prevalent and debilitating condition characterized by chronic back pain and reduced quality of life. Strontium ranelate (SRR) is a compound traditionally used for treating osteoporosis via activating TGF-β1 signaling pathway. Recent studies have proved the anti-inflammatory effect of SRR on chondrocytes. Although the exact mechanism of IVDD remains unclear, accumulating evidences have emphasized the involvement of multifactorial pathogenesis including inflammation, oxidative stress damage, and etc. However, the biological effect of SRR on IVDD and its molecular mechanism has not been investigated. Firstly, this study proved the decreased expression of Transforming Growth Factor-beta 1(TGF-β1) in degenerated human intervertebral disc tissues. Subsequently, we confirmed for the first time that SRR could promote cell proliferation, mitigate inflammation and oxidative stress in human nucleus pulposus cells in vitro via increasing the expression of TGF-β1 and suppressing the Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) pathway. The molecular docking result proved the interaction between SRR and TGF-β1 protein. To further verify this interaction, gain- and loss- of function experiments were conducted. We discovered that both TGF-β1 knockdown and overexpression influenced the activation of the NF-κB pathway. Taken together, SRR could mitigate IL-1β induced-cell dysfunction in human nucleus pulposus cells by regulating TGF-β1/NF-κB axis in vitro . Finally, the in vivo therapeutic effect of SRR on IVDD was confirmed. Our findings may contribute to the understanding of the complex interplay between inflammation and degenerative processes in the intervertebral disc and provide valuable insights into the development of targeted treatment-based therapeutics for IVDD.

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Hesperidin mitigates oxidative stress-induced ferroptosis in nucleus pulposus cells via Nrf2/NF-κB axis to protect intervertebral disc from degeneration

Cited by 14 publications

References 64 publications

Ferroptosis inhibitors: past, present and future

Ferroptosis inhibitors: past, present and future

The Pivotal Role of Nrf2 Signal Axis in Intervertebral Disc Degeneration

Strontium Ranelate Ameliorates Intervertebral Disc Degeneration via Regulating TGF-β1/NF-κB Axis

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