Discovery of Herbal Remedies and Key Components for Major Depressive Disorder Through Biased Random Walk Analysis on a Multiscale Network

Major depressive disorder (MDD) is a widespread psychiatric condition with substantial socioeconomic impacts, yet single-target pharmacotherapies often yield responses. To address its multifactorial nature, this study employed a multiscale network analysis of herbs, their active components, and MDD-associated protein targets. Using a biased random walk with restart, we calculated interactions between disease-related and herb-derived targets, identifying herbs highly correlated with MDD. Enrichment analysis further revealed key signaling pathways, including oxidative stress, neuroinflammation, and hormone metabolism, underlying these herbs' therapeutic effects. We identified <i>Ephedrae herba</i>, <i>Glehniae radix</i>, <i>Euryales semen</i>, and <i>Campsitis flos</i> as promising candidates, each containing multiple bioactive compounds (such as ephedrine, psoralen, xanthine, and ursolic acid) that modulate critical processes like oxidation-reduction, inflammatory cytokine regulation, and transcriptional control. Network visualization showed how these herbs collectively target both shared and distinct pathways, supporting a synergistic, multi-target therapeutic strategy. This approach underscores the significance of network-based methodologies in addressing complex disorders such as MDD, where focusing on a single target may overlook synergistic interactions. By integrating diverse molecular data, this study provides a systematic framework for identifying novel interventions. Future experimental validation will be crucial to confirm these predictions and facilitate the translation of findings into effective MDD therapies.