Methyl Ferulic Acid Alleviates Neuropathic Pain by Inhibiting Nox4-induced Ferroptosis in Dorsal Root Ganglia Neurons in Rats

Liu, Tielong; Qi, Wenqiang; Jia, Lei; Ma, Ketao; Si, Jun‐Qiang; Yin, Jieting; Zhao, Yujia; Dai, Zhijun; Yin, Jiangwen

doi:10.1007/s12035-023-03270-6

Cited by 15 publications

(5 citation statements)

References 40 publications

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“…Overexpression of NADPH oxidase 4 (Nox4) in DRG can cause ferroptosis and lead to NP. Methyl ferulic acid (MFA) given by gavage can alleviate the NP symptoms in SNI rats by inhibiting the increase of Nox4 in DRG ( Liu et al, 2023 ).…”

Section: New Methods For Neuropathic Pain Treatment Based On Ferroptosismentioning

confidence: 99%

Ferroptosis: a new regulatory mechanism in neuropathic pain

Li,

Guo,

Gao

et al. 2023

Front. Aging Neurosci.

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Neuropathic pain (NP) is pain caused by damage to the somatosensory system. It is a common progressive neurodegenerative disease that usually presents with clinical features such as spontaneous pain, touch-evoked pain, nociceptive hyperalgesia, and sensory abnormalities. Due to the complexity of the mechanism, NP often persists. In addition to the traditionally recognized mechanisms of peripheral nerve damage and central sensitization, excessive iron accumulation, oxidative stress, neuronal inflammation, and lipid peroxidation damage are distinctive features of NP in pathophysiology. However, the mechanisms linking these pathological features to NP are not fully understood. The complexity of the pathogenesis of NP greatly limits the development of therapeutic approaches for NP. Ferroptosis is a novel form of cell death discovered in recent years, in which cell death is usually accompanied by massive iron accumulation and lipid peroxidation. Ferroptosis-inducing factors can affect glutathione peroxidase directly or indirectly through different pathways, leading to decreased antioxidant capacity and accumulation of lipid reactive oxygen species (ROS) in cells, ultimately leading to oxidative cell death. It has been shown that ferroptosis is closely related to the pathophysiological process of many neurological disorders such as NP. Possible mechanisms involved are changes in intracellular iron ion levels, alteration of glutamate excitability, and the onset of oxidative stress. However, the functional changes and specific molecular mechanisms of ferroptosis during this process still need to be further explored. How to intervene in the development of NP by regulating cellular ferroptosis has become a hot issue in etiological research and treatment. In this review, we systematically summarize the recent progress of ferroptosis research in NP, to provide a reference for further understanding of its pathogenesis and propose new targets for treatment.

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Section: New Methods For Neuropathic Pain Treatment Based On Ferroptosismentioning

confidence: 99%

Ferroptosis: a new regulatory mechanism in neuropathic pain

Li,

Guo,

Gao

et al. 2023

Front. Aging Neurosci.

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“…In neuropathic pain induced by spared nerve injury, methyl FA demonstrates a significant alleviation of pain by inhibiting Nox4‐induced ferroptosis. The protective effects involve downregulating Nox4 expression, decreasing ACSL4, ROS, and iron content, and restoring GPX4 expression (Liu, Wang, et al, 2023). Similarly, FA showcases its potential as an antioxidant therapy against erastin‐mediated ferroptosis in murine MIN6 cells.…”

Section: Phenolic Acids and Ferroptosis In Cancermentioning

confidence: 99%

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

Zhang,

Xie

2024

Phytotherapy Research

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In recent years, heightened interest surrounds the exploration of natural phenols as potential agents for cancer therapy, specifically by inducing ferroptosis, a unique form of regulated cell death characterized by iron‐dependent lipid peroxidation. This review delves into the roles of key natural phenols, flavonoids, phenolic acids, curcumin, and stilbenes, in modulating ferroptosis and their underlying mechanisms. Emphasizing the significance of amino acid, lipid, and iron metabolism, the study elucidates the diverse pathways through which these phenols regulate ferroptosis. Notably, curcumin, a well‐known polyphenol, exhibits multifaceted interactions with cellular components involved in ferroptosis regulation, providing a distinctive therapeutic avenue. Stilbenes, another phenolic class, demonstrate promising potential in influencing lipid metabolism and iron‐dependent processes, contributing to ferroptotic cell death. Understanding the intricate interplay between these natural phenols and ferroptosis not only illuminates complex cellular regulatory networks but also unveils potential avenues for novel cancer therapies. Exploring these compounds as inducers of ferroptosis presents a promising strategy for targeted cancer treatment, capitalizing on the delicate balance between cellular metabolism and regulated cell death mechanisms. This article synthesizes current knowledge, aiming to stimulate further research into the therapeutic potential of natural phenols in the context of ferroptosis‐mediated cancer therapy.

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“…Gallic acid exacerbates chronic pain and depression symptoms by inhibiting P2X7 receptor-induced ferroptosis in CCI rats [ 121 ]. Increased levels of Nox4 in DRG can trigger ferroptosis, resulting in neuropathic pain, while Methyl ferulic acid (MFA) can relieve neuropathic pain by blocking the upregulation of Nox4 in DRG [ 122 ]. EA inhibits ferroptosis through modulation of the SAT1/ALOX15 pathway for the management of neuropathic pain [ 123 ].…”

Section: Ferroptosismentioning

confidence: 99%

New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation

Luo,

Huang

2024

IJMS

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Neuropathic pain, which refers to pain caused by a lesion or disease of the somatosensory system, represents a wide variety of peripheral or central disorders. Treating neuropathic pain is quite demanding, primarily because of its intricate underlying etiological mechanisms. The central nervous system relies on microglia to maintain balance, as they are associated with serving primary immune responses in the brain next to cell communication. Ferroptosis, driven by phospholipid peroxidation and regulated by iron, is a vital mechanism of cell death regulation. Neuroinflammation can be triggered by ferroptosis in microglia, which contributes to the release of inflammatory cytokines. Conversely, neuroinflammation can induce iron accumulation in microglia, resulting in microglial ferroptosis. Accumulating evidence suggests that neuroinflammation, characterized by glial cell activation and the release of inflammatory substances, significantly exacerbates the development of neuropathic pain. By inhibiting microglial ferroptosis, it may be possible to prevent neuroinflammation and subsequently alleviate neuropathic pain. The activation of the homopentameric α7 subtype of the neuronal nicotinic acetylcholine receptor (α7nAChR) has the potential to suppress microglial activation, transitioning M1 microglia to an M2 phenotype, facilitating the release of anti-inflammatory factors, and ultimately reducing neuropathic pain. Recent years have witnessed a growing recognition of the regulatory role of α7nAChR in ferroptosis, which could be a potential target for treating neuropathic pain. This review summarizes the mechanisms related to α7nAChR and the progress of ferroptosis in neuropathic pain according to recent research. Such an exploration will help to elucidate the relationship between α7nAChR, ferroptosis, and neuroinflammation and provide new insights into neuropathic pain management.

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Methyl Ferulic Acid Alleviates Neuropathic Pain by Inhibiting Nox4-induced Ferroptosis in Dorsal Root Ganglia Neurons in Rats

Cited by 15 publications

References 40 publications

Ferroptosis: a new regulatory mechanism in neuropathic pain

Ferroptosis: a new regulatory mechanism in neuropathic pain

Induction of ferroptosis by natural phenols: A promising strategy for cancer therapy

New Insight into Neuropathic Pain: The Relationship between α7nAChR, Ferroptosis, and Neuroinflammation

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