Li Minde, Liu Xinya
Department of Rehabilitation Medicine, Affiliated Rehabilitation Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
Medical Laboratory Department, Affiliated Mental Health Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China.
J Orthop. 2025 Jun 21;65:302-309. doi: 10.1016/j.jor.2025.06.013. eCollection 2025 Jul.
Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, and its pathogenesis involves the gradual loss of nucleus pulposus cells (NPCs). However, the molecular mechanisms linking these pathways are not yet fully understood.
This study aims to investigate the role of ferulic acid (FA) in IDD and its potential mechanisms of action, providing potential therapeutic targets for IDD.
Analysis of 10 common traditional Chinese medicine prescriptions for lumbar disc herniation revealed that ferulic acid (Ferulic acid, FA) is a major active pharmaceutical ingredient. CCK8 confirmed that FA promotes the proliferation of NP cells. Edu results showed that FA promotes NP cell proliferation, while ferroptosis inhibits NP proliferation. Moreover, FA can alleviate the inhibitory effect of ferroptosis on NP cell proliferation. Subsequently, animal experiments confirmed that FA alleviates IDD in rats, and safranin O-fast green staining results confirmed that FA has a role in alleviating IDD lesions. Analysis of the GSE15227 and GSE23130 datasets showed that GRB2 is a hub gene in the progression of IDD, and molecular docking results showed that FA can bind to GRB2. WB demonstrated that FA significantly increased the expression of IκBα in ferroptosis-induced NP cells, thereby promoting proliferation. Meanwhile, the addition of the NF-κB agonist (TNF-α) significantly reduced IκBα expression and significantly inhibited NP cell proliferation.
FA significantly inhibited ferroptosis markers and NPC proliferation in NPCs. GRB2 is one of the hub genes of IDD, and molecular docking results showed that FA has binding sites with GRB2. Meanwhile, FA upregulated IκBα, inhibiting the nuclear translocation of NF-κB and its downstream pro-inflammatory cytokines.
FA can significantly alleviate the progression of IDD. FA may inhibit NPC inflammation and lipid peroxidation through the GRB2/NF-κB pathway, The FA-GRB2/NF-κB axis is a potential therapeutic target for intervertebral disc degeneration.
椎间盘退变（IDD）是腰痛的主要原因之一，其发病机制涉及髓核细胞（NPCs）的逐渐丧失。然而，连接这些途径的分子机制尚未完全阐明。
本研究旨在探讨阿魏酸（FA）在IDD中的作用及其潜在作用机制，为IDD提供潜在的治疗靶点。
对10种常见的腰椎间盘突出症中药方剂进行分析，发现阿魏酸（Ferulic acid，FA）是主要的活性药物成分。CCK8证实FA促进NP细胞增殖。Edu结果显示FA促进NP细胞增殖，而铁死亡抑制NP增殖。此外，FA可减轻铁死亡对NP细胞增殖的抑制作用。随后，动物实验证实FA可减轻大鼠的IDD，番红O-固绿染色结果证实FA在减轻IDD病变方面具有作用。对GSE15227和GSE23130数据集的分析表明，GRB2是IDD进展中的一个枢纽基因，分子对接结果表明FA可与GRB2结合。WB证实FA显著增加铁死亡诱导的NP细胞中IκBα的表达，从而促进增殖。同时，添加NF-κB激动剂（TNF-α）可显著降低IκBα表达并显著抑制NP细胞增殖。
FA显著抑制NPCs中的铁死亡标志物和NPC增殖。GRB2是IDD的枢纽基因之一，分子对接结果表明FA与GRB2有结合位点。同时，FA上调IκBα，抑制NF-κB及其下游促炎细胞因子的核转位。
FA可显著减轻IDD的进展。FA可能通过GRB2/NF-κB途径抑制NPC炎症和脂质过氧化，FA-GRB2/NF-κB轴是椎间盘退变的潜在治疗靶点。
