Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia: Based on serum pharmacochemistry and network pharmacology

• Published in: Animal models and experimental medicine Vol. 7; no. 3; pp. 259 - 274
• Main Authors: Xu, Huirong, Dong, Meiyue, Du, Ruikun, Zhang, Chengcheng, Chen, Zinuo, Tian, Guangyu, Cui, Qinghua, Li, Kejian
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-06-2024; John Wiley and Sons Inc; Wiley
• Subjects: AKT1 protein; Blood; Chinese medicine; Chromatography; COVID-19; Disease transmission; Drug resistance; Epidemics; Experiments; Hospitals; Infections; Laboratory animals; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Medical research; network pharmacology; Original; pharmacodynamical material basis; Pharmacodynamics; Pharmacology; Pneumonia; Proteins; Respiratory syncytial virus; Scientific imaging; serum pharmacochemistry; Severe acute respiratory syndrome coronavirus 2; Software; Themed Section: Traditional Chinese Medicines and Natural Medicines Research; viral pneumonia; Viruses; YangshenDingzhi granules; Beijing China; United States > US; China; pharmacodynamical material basis; serum pharmacochemistry; network pharmacology; YangshenDingzhi granules; viral pneumonia
• ISSN: 2576-2095; 2096-5451; 2576-2095
• DOI: 10.1002/ame2.12440

Background
YangshenDingzhi granules (YSDZ) are clinically effective in preventing and treating COVID‐19. The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.
Methods
The chemical constituents of YSDZ in the blood were examined using ultra‐performance liquid chromatography‐quadrupole/orbitrap high‐resolution mass spectrometry (UPLC‐Q‐Exactive Orbitrap MS). Potential protein targets were obtained from the SwissTargetPrediction database, and the target genes associated with viral pneumonia were identified using GeneCards, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) databases. The intersection of blood component‐related targets and disease‐related targets was determined using Venny 2.1. Protein–protein interaction networks were constructed using the STRING database. The Metascape database was employed to perform enrichment analyses of Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways for the targets, while the Cytoscape 3.9.1 software was utilized to construct drug‐component‐disease‐target‐pathway networks. Further, in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.
Results
Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum. Among these, MAPK1, MAPK3, AKT1, EGFR, and TNF play significant roles. In vitro tests revealed that the medicated serum suppressed the replication of H1N1, RSV, and SARS‐CoV‐2 replicon. Further, in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.
Conclusion
The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.
We used UPLC‐Q‐Exactive Orbitrap‐MS and network pharmacology to investigate the pharmacodynamic mechanism that enables the blood components of YangshenDingzhi granules to intervene in viral pneumonia. In vitro and in vivo experiments verified that the drug inhibited H1N1, RSV, and SARS‐CoV‐2 Replicon viruses through the synergistic effects of multiple components, targets, and pathways.