Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model

Depression is a complex psychiatric disorder that poses significant treatment challenges.Qiangzhifang (QZF), a compound used in traditional Chinese medicine, demonstrates potential clinical efficacy in treating depression.However, the mechanisms of action and active ingredients of QZF have not been fully elucidated.The primary aim of this study was to elucidate the effective active ingredients and potential molecular mechanisms of QZF for the alleviation of depression by integrating network pharmacology predictions with experimental validations. We adopted a chronic restraint stress (CRS) rat model and conducted behavioral tests such as the open field test (OFT), sucrose preference test (SPT), and forced swimming test (FST) to evaluate the therapeutic effects of QZF on depression. Regarding behavioral parameters, the QZF group exhibited significantly higher body mass, sucrose preference ratio, and central zone residence time compared to the model group (P < 0.01, P < 0.01, P < 0.01), and a significantly reduced immobilization time in the forced swimming test (P < 0.001).Network pharmacology and molecular docking studies suggest that QZF may have antidepressant effects by modulating the HIF-1 and JAK-STAT pathways, with key target genes including AKT1, IL-6, MTOR, and TP53, implicated in inflammation, neuroprotection, and apoptosis.In conclusion, this study offers new insights into the modernization and development of Chinese medicine compounds for the comprehensive treatment of depression.