To investigate this hypothesis, we established chronic stress defeated stress (CSDS) depression mice model and found EDA ameliorated depressive, anxiety-like behaviors and neuronal loss, affected energy metabolism, inhibited microglial activation, OS damage and pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) activation, attenuated astrocyte dysfunction and suppressed ferroptosis and inflammation response by regulating the Sirt1/Nrf2/HO-1/Gpx4 pathway. The gene discussed is HMOX1; the disease is major depressive disorder.