Furthermore, the data have indicated that paeoniflorin can effectively improve the depression-like state in depression model rats, the behavioral profile and HPA axis can be significantly regulated in the pharmacodynamic index, and the metabolic pathways of the related indexes can be significantly recovered in the metabolomics analysis—with the mechanism possibly related to reductions in the serum levels of ACTH, CORT, and CRH [53,54]—to intervene in the neuroendocrine immune system and metabolic pathways [55]. This evidence concerns the gene CORT and major depressive disorder.