Network Pharmacology Analysis of the Mechanisms of Compound Herba Sarcandrae (Fufang Zhongjiefeng) Aerosol in Chronic Pharyngitis Treatment

Abstract

Purpose

This study aimed to investigate the molecular mechanisms of compound herba Sarcandrae aerosol, also known as the Fufang Zhongjiefeng (FFZJF) aerosol, in treating chronic pharyngitis (CP) using network pharmacology and in vivo experimental approaches.

Methods

Active compounds and putative targets of five herbs in FFZJF were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction databases. The therapeutic targets of CP were obtained from OMIM, Durgbank, DisGeNT, and GAD databases. The active compounds-target networks were constructed using Cytoscape 3.6.1. The overlapping targets of FFZJF active compounds and CP targets were further analyzed using the String database to construct protein–protein interaction (PPI) network. KEGG pathway and Gene Ontology enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery. The predicted targets and pathways were validated in a group A β-hemolytic streptococcus-induced rat CP model.

Results

There were 45 active compounds identified from FFZJF and 11 potential protein targets identified for CP treatment. PPI network demonstrated that IL6, PTGS2, TLR-4, and TNF may serve as the key targets of FFZJF for the treatment of CP. The main functional pathways involving these key targets include cytokine secretion, inflammatory response, MyD88-dependent toll-like receptor signaling pathway, toll-like receptor signaling pathway, TNF signaling pathway, and NF-κB signaling pathway. In a rat CP model, the elevation of serum TNF-α, IL1β, and IL6 levels, as well as the upregulation of TLR-4, MyD88, NF-κB P65 in the pharyngeal mucosal tissues could be effectively reduced by FFZJF treatment in a dose-dependent manner.

Conclusion

Through a network pharmacology approach and animal study, we predicted and validated the active compounds of FFZJF and their potential targets for CP treatment. The results suggest that FFZJF can markedly alleviate GAS-induced chronic pharyngitis by modulating the TLR-4/MyD88/NF-κB signaling pathways.

Keywords:

• chronic pharyngitis
• Fufang Zhongjiefeng Aerosol
• FFZJF
• network pharmacology
• TLR-4/MyD88/NF-κB signaling pathway

Acknowledgments

This research was supported by the National Natural Science Foundation of China (grant 81760882 to Yanping Zhang).

Yanping Zhang and Taohua Yuan contributed equally to this paper and should be considered as the first authors.

Ethics Statement

Ethics Approval and Consent to Participate:The experimental scheme was approved by the Experimental Animal Ethics Committee of Guizhou Medical University (Ethical number: 1709051) and followed the guidelines for the ethical review of laboratory animal welfare People’s Republic of China National Standard GB/T 35892-2018.And the experimental process is strictly in accordance with the National Institutes of Health published guidelines for the care and use of experimental animals (NIH publication 85–23, revised in 1996) and China’s guidelines for the ethical review of laboratory animal welfare.

Disclosure

The authors report no conflicts of interest in this work.