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

Huizhen Yue,1,2,* Shuhua Liu,1,* Yinglu Bai,1 Wenjing Zhu,3 Jinhao Tian,3 Xiaolong Xu,1,2 Qingquan Liu1,2 1Department of Emergency and Critical Care, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Research Laboratory of Infection and Immunity, Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Clinical Medical College, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaolong Xu, Department of Emergency and Critical Care, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China, Email [email protected] Qingquan Liu, Department of Emergency and Critical Care, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China, Email [email protected]: 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.Keywords: CaoHuangGuiXiang formula, systemic candidiasis, network pharmacology, antifungal activity, anti-inflammatory effect