The traditional Chinese medicine Chaihu Shugan San improves depression symptoms by regulating glucocorticoid metabolism and related pathways, as well as downstream signaling proteins.
In the research, depression was induced in rats via chronic unpredictable mild stress and Chaihu Shugan San's impact on this depression model was studied. High-performance liquid tandem mass spectrometry was used to verify metabolites in the rat's plasma and prefrontal cortex. The impact of Chaihu Shugan San on glucocorticoid metabolism was established through the changes in corticosterone levels and the increase of dehydrocorticosterone. Other elements of the pharmacology like glucocorticoid synthase and metabolic enzymes were also recorded for changes post the administration of Chaihu Shugan San.
Behavioral tests conducted showed a significant improvement in depression symptoms in rats, following an administration period of 8 weeks. On a molecular level, Chaihu Shugan San managed to restore glucocorticoid signaling by upregulating some proteins and downregulating others. The treatment also inhibited inflammation, particularly stronger in the liver and the prefrontal cortex than fluoxetine. Using network pharmacology, it was discovered that Chaihu Shugan San targets multiple pathways including some specified ones, demonstrating its comprehensive role in treating depression.