Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries
Wentao Duan,
Zexian Ou,
Yuxing Huang,
Yifan Zhang,
Lan Zhang,
Yanan Zhao,
Ruikun He,
Yihan Zhang,
Yuanlong Ge,
Huiling Lou,
Zhenyu Ju,
Qian Hu
Affiliations
Wentao Duan
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Zexian Ou
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Yuxing Huang
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Yifan Zhang
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Lan Zhang
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Yanan Zhao
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Ruikun He
BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China
Yihan Zhang
BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China
Yuanlong Ge
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Huiling Lou
Department of Geriatrics, National Key Clinical Specialty, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
Zhenyu Ju
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
Qian Hu
Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China
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.
