Catalpol was also shown to ameliorate depression-like behavior in mice subjected to chronic unpredictable mild stress; this appeared to involve reconditioning the hypothalamic-pituitary-adrenal (HPA) axis, and enhancing the expression of tropomyosin-related kinase B (TrkB) and brain-derived neurotrophic factor (BDNF) [23]. This evidence concerns the gene BDNF and major depressive disorder.