Tetrandrine Ameliorates Traumatic Brain Injury by Regulating Autophagy to Reduce Ferroptosis

Traumatic brain injury (TBI) is the leading cause of death and disability in trauma patients. However, the effects and mechanism of autophagy after TBI remain unclear. This study aimed to investigate whether tetrandrine could ameliorate TBI through autophagy to reduce ferroptosis. A mice model for TBI was implemented. Behavioral and histomorphological experiments were performed to evaluate outcomes of the mice. The ferroptosis levels was detected by Perls staining. Enzyme-linked immunosorbent assay (ELISA) was applied to detect malondialdehyde (MDA), glutathione (GSH), and glutathione peroxidase 4 (GPX4) levels in the brain tissue. Western blot test was performed to detect Beclin 1, light chain 3 (LC3) II/I, p62, GPX4, SCL7A11, and ferritin heavy chain 1 (FTH1) levels, and the expression of LC3B, Beclin 1, GPX4, and FTH1 in the brain tissue was detected by immunofluorescence (IF). The behavioral and histomorphological results demonstrated that tetrandrine improved the neurological function and cerebral edema on days 1, 3, and 7 after TBI. The ELISA results suggested that tetrandrine reduced the MDA concentration and increased GSH concentration on days 1, 3, and 7 after TBI. IF staining and Perls staining reflected that tetrandrine promoted autophagy and inhibited ferroptosis on days 1, 3, and 7 after TBI, respectively. Tetrandrine further improved the neurological function, cerebral edema, autophagy, and ferroptosis on days 1, 3, and 7 after TBI after adding the autophagy inducer rapamycin. The effect of TET in alleviating TBI increased with the increase of time and dose. Tetrandrine ameliorated TBI by regulating autophagy to reduce ferroptosis, providing a new therapeutic strategy for TBI.