Duan Wentao, Ou Zexian, Huang Yuxing, Zhang Yifan, Zhang Lan, Zhao Yanan, He Ruikun, Zhang Yihan, Ge Yuanlong, Lou Huiling, Ju Zhenyu, Hu Qian
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.
BYHEALTH Institute of Nutrition & Health, Guangzhou 510663, China.
Antioxidants (Basel). 2023 Dec 15;12(12):2119. doi: 10.3390/antiox12122119.
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.
铁死亡参与多种组织损伤，包括神经退行性变、缺血再灌注损伤和急性肝损伤。铁死亡抑制剂在治疗各种疾病方面展现出了有前景的临床潜力。水飞蓟素作为一种传统化学物质，已被广泛用于医疗保健和临床应用中，以治疗涉及铁死亡的肝损伤。水飞蓟宾是水飞蓟素的主要活性成分。然而，水飞蓟宾对铁死亡及铁死亡相关疾病的影响仍不清楚。在此，我们发现水飞蓟宾可抑制由铁死亡诱导剂（包括RSL3和erastin）引起的不同类型细胞的死亡。此外，水飞蓟宾可减轻RSL3诱导的脂质过氧化，而不影响不稳定铁池。接下来，通过DPPH测定法证明了水飞蓟宾的抗氧化活性。在体内，水飞蓟宾显著减轻了谷胱甘肽过氧化物酶4（GPX4）基因敲除的C57 BL/6J小鼠肝脏和肾脏中的组织损伤和铁死亡。此外，水飞蓟宾有效挽救了肾缺血再灌注，这是一种众所周知的铁死亡相关疾病。总之，我们的研究表明水飞蓟宾可有效抑制细胞铁死亡和铁死亡相关的组织损伤，这表明水飞蓟宾是一种治疗铁死亡相关疾病的潜在化学物质。
