System Pharmacology Reveals How Sinisan Treats Major Depressive Disorder

Abstract

Sinisan (SNS), a classical traditional Chinese medicine formula characterized by multicomponent and multitarget properties, has shown potential antidepressant effects; however, its underlying molecular mechanisms remain incompletely understood. This study aimed to investigate the potential molecular mechanisms of SNS against major depressive disorder (MDD) using a systems pharmacology approach.

Network pharmacology was applied to systematically identify the active compounds, potential targets, and biological pathways associated with SNS in MDD treatment. Compound–target networks, disease-related target networks, protein–protein interaction networks, and pathway enrichment analyses were constructed. Molecular docking analysis was further performed to evaluate the potential interactions between representative active compounds and core target proteins.

A total of 123 bioactive compounds and 244 potential SNS-related targets were identified. By integrating SNS-associated targets with MDD-related targets, 27 overlapping therapeutic targets were obtained. Functional enrichment analysis suggested that SNS may exert antidepressant effects through multiple biological processes and signaling pathways, including neuroactive ligand–receptor interaction, serotonergic synapse, tryptophan metabolism, drug metabolism, and steroid hormone biosynthesis. Molecular docking analysis suggested potential interactions between core targets and representative active compounds of SNS, providing preliminary computational evidence for further experimental validation.

This study provides a systems-level perspective on the potential mechanisms of SNS in MDD and suggests that SNS may regulate depression-related biological networks through multicomponent and multitarget interactions. These findings provide a theoretical basis for future experimental validation and translational research on SNS as a potential therapeutic strategy for MDD.