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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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Published in:Antioxidants 2023-12, Vol.12 (12), p.2119
Main Authors: Duan, Wentao, Ou, Zexian, Huang, Yuxing, Zhang, Yifan, Zhang, Lan, Zhao, Yanan, He, Ruikun, Zhang, Yihan, Ge, Yuanlong, Lou, Huiling, Ju, Zhenyu, Hu, Qian
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cited_by cdi_FETCH-LOGICAL-c496t-2f2c9f6bef3fcea624f588ed5c5fdffd4d660cd71b6c29f619acd8261ce86ee63
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container_issue 12
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container_title Antioxidants
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creator Duan, Wentao
Ou, Zexian
Huang, Yuxing
Zhang, Yifan
Zhang, Lan
Zhao, Yanan
He, Ruikun
Zhang, Yihan
Ge, Yuanlong
Lou, Huiling
Ju, Zhenyu
Hu, Qian
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.
doi_str_mv 10.3390/antiox12122119
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subjects Antioxidants
Cells
Drugs
Ferroptosis
Flow cytometry
Glutathione peroxidase
glutathione peroxidase 4
Injuries
Ischemia
Kidneys
Lipid peroxidation
Lipids
Liver
Liver diseases
Medical research
Medicine, Experimental
Neurodegeneration
renal ischemia reperfusion
Reperfusion
Silibinin
Silymarin
title Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries
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