Previous studies have demonstrated that icariin can ameliorate depressive-like behavior in the CUMS-induced depression rat model by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway and the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome/Caspase-1/IL-1β axis, suppressing the release of TNF-α (Liu et al., 2015). Here, TNF is linked to major depressive disorder.