This suggests that the possible anti-depressant mechanisms of Lilium saponins are as follows: (1) increasing the contents of dopamine and serotonin in the brain of depression model rats and improving the deficiency of monoamine neurotransmitters; (2) increasing the expression of glucocorticoid and corticotropin in the hippocampus and inhibiting the hyperactive hypothalamus–pituitary–adrenal axis; and (3) reducing the content of blood cortisol and corticotropin as well as the expression of hypothalamic corticotropin-releasing factor. This evidence concerns the gene POMC and major depressive disorder.