Further evidence revealed that a low dose of 30 mg/kg via oral gavage of crocin improved unpredictable chronic mild stress-induced anxiety and depression through a downregulation of brain oxidative stress, cortical malondialdehyde, inflammatory mediators (i.e., TNF-α and IL-6) and corticosterone serum levels after 4 weeks in rats [142]. This evidence concerns the gene IL6 and major depressive disorder.