Yang Han, Ye Fei, Chen Liuxu, Yang Linyu, Kang Jianping
Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, P.R. China.
Iran J Basic Med Sci. 2025;28(6):799-807. doi: 10.22038/ijbms.2025.82651.17864.
Epigallocatechin gallate (EGCG) exhibits various biological effects, including antiviral, anti-inflammatory, cardioprotective, and lipid-regulating properties. This study aims to investigate the therapeutic effects and mechanisms of EGCG in spinal cord injury (SCI).
The bioinformatic databases were used to screen therapeutic target genes for drugs against SCI. Component-Target-Disease networks were constructed with Cytoscape software, and inter-target interactions were analyzed using the String database. Additionally, KEGG pathway enrichment analyses were conducted on the identified target genes. SCI was evaluated by detecting inflammation-related factors, H&E staining, and immunohistochemistry. Furthermore, ROS and JC1 staining were performed on HT22 cells subjected to various treatments. Molecular mechanisms were investigated using western blot and qRT-PCR analyses.
Forty-four overlapping genes were identified as potential targets, with HMOX1, GPX-4, and HIF-1A emerging as central hub genes. Key pathways associated with these targets included Ferroptosis and HIF-1 signaling. studies demonstrated that EGCG effectively promotes motor function recovery and reduces the expression of proteins and genes such as IL-1β, IL-6, HIF-1α, and 4HNE. experiments showed that EGCG decreases ROS and intracellular lipid ROS levels in HT22 cells while increasing GPX-4 and HMOX1 expression to inhibit ferroptosis and HIF-1 signaling pathways.
Our findings reveal a significant new mechanism by which EGCG can reduce SCI through the inhibition of ferroptosis, facilitated by the activation of HMOX1 expression and the down-regulation of the HIF-1 signaling pathway. This suggests its potential as a therapeutic option for this condition.
表没食子儿茶素没食子酸酯（EGCG）具有多种生物学效应，包括抗病毒、抗炎、心脏保护和脂质调节特性。本研究旨在探讨EGCG对脊髓损伤（SCI）的治疗作用及其机制。
利用生物信息学数据库筛选抗SCI药物的治疗靶点基因。使用Cytoscape软件构建成分-靶点-疾病网络，并通过String数据库分析靶点间的相互作用。此外，对鉴定出的靶点基因进行KEGG通路富集分析。通过检测炎症相关因子、苏木精-伊红（H&E）染色和免疫组织化学来评估SCI。此外，对接受各种处理的HT22细胞进行活性氧（ROS）和JC1染色。采用蛋白质免疫印迹法（western blot）和实时定量聚合酶链反应（qRT-PCR）分析研究分子机制。
鉴定出44个重叠基因作为潜在靶点，其中血红素加氧酶-1（HMOX1）、谷胱甘肽过氧化物酶4（GPX-4）和缺氧诱导因子-1α（HIF-1A）成为核心枢纽基因。与这些靶点相关的关键通路包括铁死亡和HIF-1信号传导。研究表明，EGCG能有效促进运动功能恢复，并降低白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、HIF-1α和4-羟基壬烯醛（4HNE）等蛋白质和基因的表达。实验表明，EGCG可降低HT22细胞中的ROS和细胞内脂质ROS水平，同时增加GPX-4和HMOX1的表达，以抑制铁死亡和HIF-1信号通路。
我们的研究结果揭示了一种重要的新机制，即EGCG可通过抑制铁死亡来减轻SCI，这一过程由HMOX1表达的激活和HIF-1信号通路的下调所促进。这表明其作为这种疾病治疗选择的潜力。
