Network pharmacology and molecular docking for exploring the mechanism of Hedyotis diffusa against hepatitis B virus infection.

BACKGROUND

Hepatitis B virus (HBV) chronically infects nearly 250 million people and causes nearly 700 000 deaths annually. Hedyotis diffusa (HD) is widely used in traditional Chinese medicine for HBV-related liver diseases, yet its systemic mechanism remains unclear.

OBJECTIVES

To elucidate the anti-HBV mode of action of HD by integrating network pharmacology with molecular docking.

METHODS

Three databases, including TCMSP, TCMID and Chemical database were used to collect ingredients. PubChem database was used to collect the known targets and Pharmmapper database for the prediction of chemicals. DisGeNET database, PharmGKB and Drugbank were used to get disease-related targets. Mapping all candidate targets transformed into gene symbols to disease-related targets. Biological analysis contains Gene Ontology analysis and enrichment analysis of KEGG signaling pathway analyzed on DAVID 6.8 database.

RESULTS

One hundred and forty-five putative HD-HBV targets emerged; 30 met hub criteria, with AKT1, ALB and GAPDH highest-ranked. GO terms centred on negative regulation of apoptosis, enzyme binding and MAP-kinase activity. Fifty-eight KEGG pathways were enriched, foremost TNF, FoxO, estrogen, prolactin and ErbB signalling. The ingredient-target-pathway network implicated ferulic acid, coumarin and digitolutein as core components. Ferulic acid docked favourably to all seven selected kinases (-7.1 to -5.3 kcal mol-¹), suggesting direct modulation of viral entry (EGFR), replication (AKT1) and immune-evasion (MAPK) checkpoints.

CONCLUSION

This study elucidates the multi-component, multi-target and multi-pathway mechanisms of HD in treating HBV infections, thereby providing an efficient and systematic preliminary direction for elucidating the complex actions of traditional Chinese medicine (TCM) formulations and guiding subsequent experiments.