Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress
BackgroundIntervertebral 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...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1501725/full |
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| author | Zaishi Zhu Zeling Huang Chaofeng Zhang Bo Xu Hua Chen Shuai Pei Baofei Zhang Lishi Jie Xiaoqing Shi Yujiang Liu Yuwei Li Yuwei Li Xiaofeng Shen Xiaofeng Shen |
| author_facet | Zaishi Zhu Zeling Huang Chaofeng Zhang Bo Xu Hua Chen Shuai Pei Baofei Zhang Lishi Jie Xiaoqing Shi Yujiang Liu Yuwei Li Yuwei Li Xiaofeng Shen Xiaofeng Shen |
| author_sort | Zaishi Zhu |
| collection | DOAJ |
| description | BackgroundIntervertebral 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.MethodsThis 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.ResultsExperimental 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.ConclusionThe alleviation of disc degeneration ferroptosis by GA may be closely associated with the key ferroptosis proteins P53 and NRF2. |
| format | Article |
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| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-1eb402ff542741cea61b41dc88767f782025-02-03T06:33:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-02-011610.3389/fphar.2025.15017251501725Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stressZaishi Zhu0Zeling Huang1Chaofeng Zhang2Bo Xu3Hua Chen4Shuai Pei5Baofei Zhang6Lishi Jie7Xiaoqing Shi8Yujiang Liu9Yuwei Li10Yuwei Li11Xiaofeng Shen12Xiaofeng Shen13Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaJiangsu Province Hospital of TCM Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaOrthopaedic Traumatology Institute, Suzhou Academy of Wumen Chinese Medicine, Suzhou, Jiangsu, ChinaSuzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, ChinaOrthopaedic Traumatology Institute, Suzhou Academy of Wumen Chinese Medicine, Suzhou, Jiangsu, ChinaBackgroundIntervertebral 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.MethodsThis 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.ResultsExperimental 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.ConclusionThe alleviation of disc degeneration ferroptosis by GA may be closely associated with the key ferroptosis proteins P53 and NRF2.https://www.frontiersin.org/articles/10.3389/fphar.2025.1501725/fullferroptosisintervertebral disc degenerationoxidative stressnucleus pulposusgallic acid |
| spellingShingle | Zaishi Zhu Zeling Huang Chaofeng Zhang Bo Xu Hua Chen Shuai Pei Baofei Zhang Lishi Jie Xiaoqing Shi Yujiang Liu Yuwei Li Yuwei Li Xiaofeng Shen Xiaofeng Shen Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress Frontiers in Pharmacology ferroptosis intervertebral disc degeneration oxidative stress nucleus pulposus gallic acid |
| title | Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress |
| title_full | Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress |
| title_fullStr | Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress |
| title_full_unstemmed | Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress |
| title_short | Gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress |
| title_sort | gallic acid protects intervertebral disc cells from ferroptosis and alleviates intervertebral disc degeneration by regulating key factors of oxidative stress |
| topic | ferroptosis intervertebral disc degeneration oxidative stress nucleus pulposus gallic acid |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1501725/full |
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