Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis

• DOI: 10.1007/s12035-022-03014-y
• Publication Date: 2022-09-07T02:02:21Z
• Authors: Heping Zhang; Wei Zhou; Jianling Li; Zhaohui Qiu; Xiaotong Wang; Hui Xu; Huadong Wang; Daxiang Lu; Renbin Qi
• Keywords: 0301 basic medicine; Amyloid beta-Peptides; Apoptosis; Lipids; PC12 Cells; Peptide Fragments; Rats; 3. Good health; Oxidative Stress; 03 medical and health sciences; Alzheimer Disease; Animals; Ferroptosis; Humans; Reactive Oxygen Species; Drugs, Chinese Herbal

Abstract Oxidative stress is one of the pathological mechanisms of Alzheimers disease (AD), and ferroptosis has been determined to be involved in neurodegenerative diseases such as AD. Senegenin (Sen) prevents oxidative damage in nerve cells via a mechanism that may be highly related to ferroptosis. However, the mechanism of ferroptosis pathway involvement in AD is unclear. In this study, we established a model of PC12 cytotoxic injury induced by Aβ25−35, and we detected the level of oxidative damage, MMP, and ferroptosis-related proteins expression. The results showed that, compared with control group, the level of ROS increased, GPX activities decreased, and MDA levels increased in Aβ25−35 group. Aβ25−35 could induce mitochondrial depolarization in PC12 cells and Fer-1 could not reverse this damage. WB revealed that Aβ25−35 group had increased ACSL4 and PEBP1 proteins, and decreased GPX4 protein. After adding Sen in the model, the level of oxidative damage was reduced, and mitochondrial depolarization was reversed compared with Aβ25−35 group. WB suggested that the expression of ACSL4 and PEBP1 proteins decreased, and the expression of GPX4 protein increased by Sen treatment. In conclusion, we found that Sen exhibits strong neuroprotective activity against Aβ25−35 induced oxidative damage and lipid metabolic associated with ferroptosis. Inhibiting nerve cells ferroptosis might facilitate the future development of strategies to AD.