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已发表论文
探究抑郁症中的铁死亡相关基因：分子机制及潜在疗法的新见解
Authors Li P , Gao Y, Li M, Du S, Zhao X, Zhou Y
Received 2 May 2025
Accepted for publication 7 October 2025
Published 31 October 2025 Volume 2025:18 Pages 6581—6593
DOI https://doi.org/10.2147/IJGM.S538103
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Woon-Man Kung
Pengpeng Li,1,2 Yangyang Gao,3 Miaobo Li,4 Shiqing Du,2 Xudong Zhao,2 Yiting Zhou2
1Department of Neurosugery, Xi’an Aerospace Hospital of Northwest University, Xi’an, Shaanxi, 710000, People’s Republic of China; 2Department of Interventional Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214125, People’s Republic of China; 3Department of Critical Care Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 4Department of Critical Care Medicine, the Second Hospital of Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China
Correspondence: Xudong Zhao, Department of Interventional Radiology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214125, People’s Republic of China, Email 9862022148@jiangnan.edu.cn Yiting Zhou, Email 17321274921@163.com
Objective: This study aimed to investigate the role of ferroptosis-related genes in depression pathogenesis and identify potential therapeutic strategies through integrated bioinformatics and traditional Chinese medicine (TCM) approaches.
Methods: We analyzed the GSE38206 dataset comprising peripheral blood mononuclear cell samples from 9 MDD patients and 9 healthy controls. Bioinformatics analyses including differential expression screening, functional enrichment, and protein-protein interaction network construction were performed to identify ferroptosis-associated hub genes. Potential therapeutic agents were screened through connectivity mapping and TCM network pharmacology analysis.
Results: Our analysis identified 60 ferroptosis-related differentially expressed genes and revealed 17 core genes that form a central regulatory network in depression. These genes are primarily involved in inflammatory response, iron metabolism, and oxidative stress pathways. We identified five potential small-molecule compounds (VX-702, gossypol, atomoxetine, TWS-119, and ibudilast) that may target these ferroptosis-related pathways. Additionally, network pharmacology analysis revealed several TCM compounds (including ginseng, saffron, and Salvia miltiorrhiza) that demonstrate multi-target regulatory capabilities consistent with TCM treatment principles.
Conclusion: This study provides evidence supporting the involvement of ferroptosis-related mechanisms in depression and proposes a integrative treatment strategy combining targeted molecular interventions with TCM approaches. The findings offer new perspectives for developing therapeutic interventions, particularly for treatment-resistant depression.
Keywords: depression, ferroptosis, bioinformatics, traditional chinese medicine, oxidative stress
1Department of Neurosugery, Xi’an Aerospace Hospital of Northwest University, Xi’an, Shaanxi, 710000, People’s Republic of China; 2Department of Interventional Radiology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214125, People’s Republic of China; 3Department of Critical Care Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 4Department of Critical Care Medicine, the Second Hospital of Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China
Correspondence: Xudong Zhao, Department of Interventional Radiology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Wuxi, 214125, People’s Republic of China, Email 9862022148@jiangnan.edu.cn Yiting Zhou, Email 17321274921@163.com
Objective: This study aimed to investigate the role of ferroptosis-related genes in depression pathogenesis and identify potential therapeutic strategies through integrated bioinformatics and traditional Chinese medicine (TCM) approaches.
Methods: We analyzed the GSE38206 dataset comprising peripheral blood mononuclear cell samples from 9 MDD patients and 9 healthy controls. Bioinformatics analyses including differential expression screening, functional enrichment, and protein-protein interaction network construction were performed to identify ferroptosis-associated hub genes. Potential therapeutic agents were screened through connectivity mapping and TCM network pharmacology analysis.
Results: Our analysis identified 60 ferroptosis-related differentially expressed genes and revealed 17 core genes that form a central regulatory network in depression. These genes are primarily involved in inflammatory response, iron metabolism, and oxidative stress pathways. We identified five potential small-molecule compounds (VX-702, gossypol, atomoxetine, TWS-119, and ibudilast) that may target these ferroptosis-related pathways. Additionally, network pharmacology analysis revealed several TCM compounds (including ginseng, saffron, and Salvia miltiorrhiza) that demonstrate multi-target regulatory capabilities consistent with TCM treatment principles.
Conclusion: This study provides evidence supporting the involvement of ferroptosis-related mechanisms in depression and proposes a integrative treatment strategy combining targeted molecular interventions with TCM approaches. The findings offer new perspectives for developing therapeutic interventions, particularly for treatment-resistant depression.
Keywords: depression, ferroptosis, bioinformatics, traditional chinese medicine, oxidative stress