Exploring the Mechanism of CaoHuangGuiXiang Formula in Ameliorating Systemic Candida albicans Infection: A Study Integrating Network Pharmacology and Animal Experiments.

PURPOSE: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine (TCM) used for the treatment of Candida-related infections. In this study, we adopted a comprehensive approach integrating network pharmacology and animal validation to investigate the potential targets and underlying mechanisms of the CHGX formula against systemic candidiasis.

METHODS

Active ingredients and potential targets of CHGX were identified via the TCMSP, Swiss Target Prediction, and TCMID databases. Systemic Candida infection targets were retrieved from the GeneCards and OMIM databases. The protein-protein interaction (PPI) network of common targets was constructed via STRING, followed by topological analysis to identify hub nodes. Functional enrichment analyses were conducted via Metascape. Molecular docking studies were performed via AutoDock. A murine model of systemic Candida albicans infection was established to evaluate the therapeutic efficacy of CHGX formula.

RESULTS

A total of 103 active compounds and 279 potential targets of the CHGX formula were identified, yielding 53 common targets between Candida infection-related targets and drug-related targets. Topological analysis of the PPI network identified 15 core targets, 25 significantly enriched KEGG pathways, and 38 enriched GO terms. Molecular docking studies demonstrated robust binding affinity between key CHGX compounds and the identified core targets. In vivo animal experiments revealed that CHGX significantly reduced mortality, improved body weight, mitigated renal pathology, decreased the kidney index, reduced the fungal burden, and alleviated tissue damage in systemic Candida infection. Furthermore, CHGX exerts immunomodulatory and anti-inflammatory effects by modulating macrophage and Th17/Treg cell populations, as well as by regulating cytokines levels.

CONCLUSION

This study elucidates the potential multi-pathway and multi-target mechanisms underlying the therapeutic efficacy of the CHGX formula against Candida infectious diseases, indicating its potential as a novel alternative antifungal drug and providing a scientific basis for its clinical application and further development.