18β-glycyrrhetinic acid protects neuronal cells from ferroptosis through inhibiting labile iron accumulation and preventing coenzyme Q10 reduction

Ferroptosis is a new form of iron-dependent cell death. A growing body of evidence suggests that abnormal ferroptosis is involved in developing neurodegenerative diseases. 18β-glycyrrhetinic acid (GA) is a major bioactive component of licorice with multiple biological activities including neuroprotection. Give the role of ferroptosis in the neurodegenerative diseases, we hypothesized that the neuroprotective effect of GA might be associated with its ability to protect neuro-cells from ferroptosis. Results demonstrated that GA was able to prevent a well-known ferroptosis inducer ferroptosis inducer 56 (FIN56)-triggered ferroptosis in HT22 mouse neuronal cell. Further mechanistic investigation revealed that the protection of GA on ferroptosis is attributed its inhibiting effect on cellular labile iron accumulation and up-regulating coenzyme Q10 (CoQ10) levels. The findings of the present study uncovered a novel mechanism involved in the neuroprotective effect of GA, and imply that GA could be developed as a novel agent to manage ferroptosis-related diseases. •GA inhibits neuro-cells from Fin56-induced ferroptosis.•GA suppresses Fin56-induced LIP and LPO.•GA reverses Fin56-induced CoQ10 reduction.