The PI3K/AKT pathway is suggested as the mechanism by which Chaihu Shugan San treats major depressive disorder, with quercetin and luteolin identified as active compounds.
The active ingredients in Chaihu Shugan San (CSS), a traditional Chinese medicine used to treat depression, were identified by screening the Traditional Chinese Medicine Systems Pharmacology database. The relevant data sets (DisGeNET, Therapeutic Target Database and DrugBank databases) were used to identify depression-related targets. Subsequently, a compound-depression target network was created from the common targets of the active compounds in CSS and major depressive disorder (MDD). Further functional enrichment analysis, protein-protein interaction analysis, and molecular docking were carried out to identify hub targets and to understand the underlying molecular mechanisms.
Experiments were conducted using mice experiencing chronic unpredictable mild stress, with and without CSS treatment. These tests demonstrated that CSS improved signs of depression and promoted neurogenesis in the subjects. Also, measurements revealed increased levels of certain types of enzymes in the hippocampus of the treated mice. The primary active compounds showing good docking scores targeting the PI3K protein were identified as quercetin and luteolin.
