Integrating network pharmacology, molecular docking, and molecular dynamics simulations to explore potential compounds and mechanisms of Coptis chinensis in treating streptococcal infections.

Background: Coptis chinensis, a prominent herb in traditional Chinese medicine, is widely utilized for its therapeutic effects against Streptococcus infections, though its precise mechanisms of action remain insufficiently understood. This study aims to clarify the potential mechanisms and active compounds of C. chinensis in the treatment of Streptococcus. Methods: Active compounds of C. chinensis were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and their potential targets were predicted from multiple public resources. These targets were intersected with streptococcus-related genes to identify overlapping targets, which were then used to construct a protein-protein interaction (PPI) network and screen for key hub genes. To investigate the pharmacological mechanisms, Gene Ontology and KEGG pathway enrichment analyses were performed. Molecular docking was employed to evaluate the binding affinities between active compounds and core target proteins, followed by molecular dynamics simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) calculations to assess binding stability and free energy. Results: A total of 24 active compounds were identified, along with 180 overlapping targets related to streptococcal infection. PPI network analysis revealed ten key hub genes, including IL1β, IL6, and MMP9. Enrichment analysis suggested that C. chinensis may inhibit the TLR4/NF-κB inflammatory pathway to modulate host immunity and mediate lipid metabolism reprogramming to restrict pathogen proliferation. Several core targets were also enriched in pathways related to extracellular matrix remodeling and immune regulation, indicating potential indirect effects on host-pathogen interface interactions. Molecular docking and simulation confirmed stable binding between major active ingredients and streptococcus-associated proteins. Conclusion: This study provides mechanistic insights into the multi-component, multi-target, and multi-pathway effects of C. chinensis against streptococcal infections. The findings offer a theoretical basis for future experimental validation and clinical translation.