Therefore, we used the LPS-induced depression mouse model to detect the effects of GP-14 on the depression behavior; then we assayed the activation of NF-κB pathway and the expression levels of IL-1β, IL-6, and TNF-α in the serum and hippocampus; finally, the possible mechanisms of GP-14 were investigated in C8 cell lines and primary astrocytes. The gene discussed is NFKB1; the disease is major depressive disorder.