The Therapeutic Effect and Potential Pharmacological Mechanisms of Ding-Zhi-Xiao-Wan on Depression were Investigated by Meta-analysis, Network Pharmacology and Molecular Docking

Abstract

Introduction: Ding-Zhi-Xiao-Wan (DZXW) produces potential antidepressant-like effects. However, its antidepressant mechanisms are still unclear. Objective: To analyze the antidepressant effects and the pharmacological mechanisms of DZXW, meta-analysis, network pharmacology, and molecular docking were selected in this study. Methods: The compounds of DZXW and genes associated with compounds or depression were obtained from databases. The genes overlapping between DZXW compounds and depression were compared by Venn diagram. A network of medicine-ingredients-targets-disease was constructed, visualized, and analyzed. Protein-protein interaction, gene ontology, pathway enrichment, and molecular docking were performed to evaluate the potential mechanisms of DZXW for the treatment of depression. Results: Meta-analysis showed that the antidepressant-like effects were produced by DZXW. The network pharmacology analysis showed that a total of 74 compound-related genes and 12607 PTSD-related genes were identified in the databases with 65 overlapping genes. The active ingredients derived from DZXW (i.e Beta-sitosterol, Stigmasterol, Fumarine, Hederagenin) elicited the antidepressant-like effects by targets, such as ACHE, HTR2A, and CHRM1. Moreover, the signaling pathways, like neuroactive ligand-receptor interaction, pathways in cancer, and cholinergic synapse, might play important roles in the treatment of depression by DZXW. Conclusion: This study provides studies analysis and molecular evidence with the beneficial effects of DZXW for the treatment of depression.