Systems Pharmacology-Based Research on the Mechanism of Danzhi Xiaoyao San in the Treatment of Depression

Depression is a common and serious mental disorder characterized by persistent feeling of sadness and loss of interest in activities. Despite conventional treatments can improve depression symptoms and prevent a recurrence, complementary and alternative therapies are necessary to be involved because of the detrimental effects of the current therapy. Traditional Chinese Medicine (TCM) formulas are considered to be a potential complementary method with special advantages for treating the multiple pathogenesis of depression in a holistic way. However, the underlying pharmacological mechanism of TCM formula on depression therapy remained elusive. Therefore, in current study, a systems pharmacology approach integrating Absorption, Distribution, Metabolism, and Excretion (ADME) filtering, target fishing, gene enrichment analysis, network pharmacology, and pathway analysis was developed to comprehensively explore the multiple therapeutic mechanisms of Danzhi Xiaoyao San (DZXYS) for the treatment of depression. Finally, 111 active components and 112 potential targets of DZXYS were identified through ADME filtering and target fishing. Gene enrichment analysis found that DZXYS played a significant role in treating depression through the regulation of multiple pathogenesis including neurotransmitter systems imbalance, brain derived neurotrophic factor, hypothalamic-pituitary-adrenal axis dysregulation, inflammation, and immune. Moreover, the compound-target and target-pathway networks were constructed to elucidate the therapeutic mechanism of DZXYS from the system perspective. This study proposes a promising way for facilitating in-depth understanding of the complicated therapeutic mechanism of TCM on depression.