Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries
Ferroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthca...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/12/2119 |
| _version_ | 1797382232137007104 |
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| author | Wentao Duan Zexian Ou Yuxing Huang Yifan Zhang Lan Zhang Yanan Zhao Ruikun He Yihan Zhang Yuanlong Ge Huiling Lou Zhenyu Ju Qian Hu |
| author_facet | Wentao Duan Zexian Ou Yuxing Huang Yifan Zhang Lan Zhang Yanan Zhao Ruikun He Yihan Zhang Yuanlong Ge Huiling Lou Zhenyu Ju Qian Hu |
| author_sort | Wentao Duan |
| collection | DOAJ |
| description | Ferroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases. |
| first_indexed | 2024-03-08T21:02:27Z |
| format | Article |
| id | doaj.art-52b846233cd14be4941861e864b28bb7 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-08T21:02:27Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-52b846233cd14be4941861e864b28bb72023-12-22T13:48:37ZengMDPI AGAntioxidants2076-39212023-12-011212211910.3390/antiox12122119Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue InjuriesWentao Duan0Zexian Ou1Yuxing Huang2Yifan Zhang3Lan Zhang4Yanan Zhao5Ruikun He6Yihan Zhang7Yuanlong Ge8Huiling Lou9Zhenyu Ju10Qian Hu11Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaBYHEALTH Institute of Nutrition & Health, Guangzhou 510663, ChinaBYHEALTH Institute of Nutrition & Health, Guangzhou 510663, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaDepartment of Geriatrics, National Key Clinical Specialty, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaKey Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, ChinaFerroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases.https://www.mdpi.com/2076-3921/12/12/2119ferroptosissilibininglutathione peroxidase 4renal ischemia reperfusion |
| spellingShingle | Wentao Duan Zexian Ou Yuxing Huang Yifan Zhang Lan Zhang Yanan Zhao Ruikun He Yihan Zhang Yuanlong Ge Huiling Lou Zhenyu Ju Qian Hu Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries Antioxidants ferroptosis silibinin glutathione peroxidase 4 renal ischemia reperfusion |
| title | Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries |
| title_full | Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries |
| title_fullStr | Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries |
| title_full_unstemmed | Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries |
| title_short | Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries |
| title_sort | silibinin inhibits cell ferroptosis and ferroptosis related tissue injuries |
| topic | ferroptosis silibinin glutathione peroxidase 4 renal ischemia reperfusion |
| url | https://www.mdpi.com/2076-3921/12/12/2119 |
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