Exploring the Patent Medication Rules and Mechanisms of Traditional Chinese Medicine Formulas for the Treatment of Depression Based on Data Mining and Network Pharmacology

Objectives: Traditional Chinese medicine (TCM) prescriptions for the treatment of major depressive disorder (MDD) were retrieved via the China Patent Publication Network. Information on the name, flavor, property, and meridian tropism of the herbal ingredients was extracted. Data analysis was conducted using Microsoft Excel 2016, and the Ancient and Modern TCM Medical Case Platform (2.3.7). This analysis included frequency assessment of medication use, categorization by properties such as flavor and nature, meridian distribution, and application of association rule analysis, clustering analysis, and complex network analysis to identify core drugs. Active ingredients of the core drugs were determined using the TCMSP database (2.3) and UniProt for target prediction and standardization. MDD-related targets were sourced from the OMIM and GeneCards databases. Potential targets for the core drugs in treating depression were identified through the Venny online platform (2.1). Protein-protein interaction (PPI) networks and key targets analysis were performed using the STRING database (12.0). The core drug components were visualized using Cytoscape (3.10) Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the potential targets were conducted using MetaScape and R (4.3.2) software.Results: We compiled a total of 162 TCM prescriptions, incorporating 346 distinct TCM herbs, with a cumulative usage frequency of 1,696 instances. Among these 346 TCM herbs, the most frequently prescribed categories were warm, neutral, and cold herbs. The dominant tastes were sweet, bitter, and pungent. The principal targeted meridians included the Liver, Heart, Lung, Spleen, Kidney, and Stomach channels. The prevailing therapeutic actions centered on soothing the Liver and relieving depression, reinforcing Yang energy, and dispelling exterior heat. Moreover, association rule analysis revealed ten recurrent TCM ingredient combinations for MDD therapy, comprising ingredients such as Angelicae Sinensis (Danggui), Bupleuri Radix (ChaiHu), Glycyrrhiza (Licorice), Ziziphi Jujubae (SuanZaoRen), Paeoniae Alba Radix (BaiShao), and Poria (FuLing), among others. Notably, the combination { Angelicae Sinensis, Poria }, followed by Bupleuri Radix received the strongest support. Cluster analysis yielded four discernible clusters. Network analysis highlighted Angelicae Sinensis, Poria, and Bupleuri Radix as central components in the structure of TCM prescription networks. Utilizing Angelicae Sinensis, Poria, and Bupleuri Radix in network pharmacological investigations suggested that the chief active constituents of these core TCM remedies—Angelicae Sinensis, Poria, and Bupleuri Radix—may include compounds such as 6,7,3',8'-tetramethoxylignane, Alexandrin, Areapillin, β-sitosterol, Cubebin, Ergosta-7,22E-dien-3β-ol, Ergosterol, Hederagenin, Hyperin, Kaempferol, Longikaurin A, Purerin, Stigmasterol, α-spinasterol, and β-actin acetate. These compounds are potentially capable of interacting with pivotal targets, including TP53, JUN, AKT1, STAT3, IL6, SRC, TNF, ESR1, MAPK1, EGFR, BCL2, FOS, PRKACA, and IL1B, thereby regulating pathways involved in various diseases and conditions.Conclusion: The analysis of patented traditional Chinese medicine (TCM) compound formulas for the treatment of depression predominantly highlights core drugs, including Angelicae Sinensis, Poria, and Bupleuri Radix. The proposed mechanism of action for these drugs suggests a profound involvement in immune system signaling pathways and the regulation of neuroinflammation.