Assessment of IL-1β upstream signaling pathways revealed that muscone inhibited the activation of NLRP3 inflammasome through downregulation in protein expression of caspase-1 and NLRP3 and suppressed the expression of key proteins in the TLR4/MyD88 pathway of the prefrontal cortex of mice with LPS-induced depression. Here, MYD88 is linked to major depressive disorder.