Arctigenin exhibits significant antidepressant effects in rodent models of depression, attenuates microglial activation and neuroinflammation through HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signaling pathways, and inhibits IDO increase and decrease in 5-HT (111). This evidence concerns the gene HMGB1 and major depressive disorder.