Berberine has been observed to significantly decrease the resting time of TST and FST in mice with depression, while concurrently elevating the levels of NE and 5-HT in the hippocampus and prefrontal cortex, and the mechanism of action of berberine is believed to be linked to the regulation of monoamine neurotransmitters in the brain (Peng et al., 2007) (Figure 1; Table 4).5-HT may contribute to the pathophysiology of depression via the cAMP/PKA/CREB signaling pathway, which is mediated by the 5-HT1A receptor (Brites and Fernandes, 2015). This evidence concerns the gene CREB1 and major depressive disorder.