The mechanism by which icariin improves depression may be related to the promotion of cell proliferation, peripheral nerve regeneration, improvement of the function of damaged nerve regulation, decrease in glucocorticoid receptors (GRs) and 5-hydroxytryptamine 1A (5-HTR1A) receptors in the hippocampus and prefrontal cortex, regulation of the central neuroendocrine system, or restoration of the negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis.[40–42] Furthermore, icariin may ameliorate prenatal restraint stress-induced depression-like behavior.[43]. The gene discussed is NR3C1; the disease is major depressive disorder.