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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 |
doi: 10.3389/fphar.2025.1501725
This article is part of the Research Topic The Pharmacological Effects and Mechanisms of Drugs Against Human Diseases by Modulating Redox Homeostasis - Volume II View all 4 articles
Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress
Provisionally accepted
Zaishi Zhu 1
Zeling Huang 1
Chaofeng Zhang 1* Bo Xu 1* Hua Chen 1* Shuai Pei 1*
Baofei Zhang 1
Lishi Jie 2
Xiaoqing Shi 1 Yu'ji'ang Liu 1* Yuwei LI 1*
Xiaofeng Shen 1*- 1 Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu Province, China
- 2 Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China
Intervertebral disc degeneration (IDD) is a chronic degenerative disease and one of the main causes of low back pain (LBP). Currently, there is no effective treatment. Ferroptosis is a cell-regulated process that depends on iron deposition and lipid peroxidation. Inhibiting ferroptosis in nucleus pulposus cells is considered a potential strategy for the treatment of IDD. Gallic acid (GA) is naturally present in a variety of plants and has anti-inflammatory, antioxidant and analgesic effects. It has been shown to alleviate ferroptosis. However, the role of GA in IDD ferroptosis remains unclear. This study explored the pathological mechanism of GA in IDD in relation to ferroptosis: (1) to identify ferroptosis-related targets for GA treatment of IDD using network pharmacology and molecular docking technology, (2) to evaluate the therapeutic effect of GA in an IDD rat model and changes in ferroptosis-related targets, (3) to investigate the changes of oxidative stress and lipid peroxidation products in NP cells after GA intervention, and (4) to study the changes of ferroptosis-related proteins and iron ions in cells and mitochondria after GA intervention. Experimental results confirmed that GA can treat IDD by reducing the degradation of extracellular matrix (ECM) and pathological changes in IDD. GA can also mitigate ferroptosis by reducing oxidative stress and lipid peroxidation in rat nucleus pulposus (NP) cells. The alleviation of disc degeneration ferroptosis by GA may be closely associated with the key ferroptosis proteins P53 and NRF2.
Keywords: Ferroptosis1, intervertebral disc degeneration2, Oxidative Stress3, nucleus pulposus4, gallic acid5
Received: 25 Sep 2024; Accepted: 17 Jan 2025.
Copyright: © 2025 Zhu, Huang, Zhang, Xu, Chen, Pei, Zhang, Jie, Shi, Liu, LI and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chaofeng Zhang, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 210023, Jiangsu Province, China
Bo Xu, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 210023, Jiangsu Province, China
Hua Chen, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 210023, Jiangsu Province, China
Shuai Pei, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 210023, Jiangsu Province, China
Yu'ji'ang Liu, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 210023, Jiangsu Province, China
Yuwei LI, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 210023, Jiangsu Province, China
Xiaofeng Shen, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 210023, Jiangsu Province, China
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