Additionally, berberine significantly downregulated the contents of IL-1β, IL-18, pro-IL-1β, pro-IL-18, and TNF-α in the hippocampus of the CUMS-induced depression mouse model by inhibiting the activity of microglia and downregulating the expression of tripartite motif 65 (Trim65), NLRP3, caspase-1, apoptosis-associated speckle-like protein (ASC), and gasdermin D (GSDMD) (Yang et al., 2023). This evidence concerns the gene CASP1 and major depressive disorder.