Study on the Mechanism of ND for Treating Depression Based on “Blood Components-Network Pharmacology”

Objective To identify blood-absorbed components of Ninglung Deshee (ND) using liquid chromatography-mass spectrometry (LC-MS), and to investigate the mechanism of ND for treating depression using network pharmacology and molecular docking methods. Methods Ultra-high-performance liquid chromatography coupled with quadrupole electrostatic field orbitrap tandem high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to identify the components of ND in the blood. Potential target sites of these chemical components were identified using the SwissADME database, while disease-related targets for depression were selected from the GeneCards database. Intersecting targets between the two databases were then identified. Cytoscape software was used to construct a “component-target-disease” network to screen the core components of ND relevant to the treatment of depression. The STRING platform was used to construct a protein-protein interaction (PPI) network of the intersecting targets to identify the core targets of ND for treating depression. Gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the DAVID platform. Schrödinger software was used to determine molecular docking of the core components and core target proteins. Results Seventy-six blood components associated with 747 drug targets were identified,. Of the 2,000 depression-related targets, 212 overlapped with those of ND. A total of 16 core targets and 16 core components were identified. The GO function and KEGG pathway enrichment analyses indicated that treatment of depression with ND ’ s may be related closely to the mitogen-activated protein kinase (MAPK) signaling and Prion disease signaling pathways. The molecular docking results showed that piperine had the highest binding energy with tumor necrosis factor (TNF). Conclusion The core components of ND such as piperine, liquiritigenin, and piperanine may act on targets including TNF, mitogen-activated protein kinase 3(MAPK3), estrogen receptor 1 (ESR1, and interleukin-6(IL-6), resulting in regulation of signaling pathways such as MAPK, TNF, and Prion disease involved in the treatment of depression. Accordingly, TNF as a therapeutic target and signaling pathway for ND to treat depression warrants further study, while other potential mechanisms and effector molecules of ND for treating depression require further detailed investigation.