Inhibitory Effects of D-Limonene and 2-Zinol on Candida Albicans Were Studied Based on Antibacterial Experiments and Network Pharmacology
Objective:Bacteriostasis experiment was conducted to study in vitro anti-candida albicans effect of D-limonene and 2-Zinol of couplet medicinals of Fructus cnidii and Borneolum Syntheticum,and network pharmacology was utilized to predict the core targets and pathways of D-limonene and 2-Zinol in the treatment of candidiasis.Methods:Taking Candida albicans as the research object,K-B disk diffusion method was used to determine the diameter of the antibacterial zone of 0.5,1.0,and 1.5 mg of D-limonene,2-Zinol,and nystatin in the drug solution,respectively.The minimum inhibitory concentration(MIC)and the combined MIC of D-limonene and 2-Zinol were determined by tube double dilution method and checkerboard method,and the combined inhibitory fraction(FIC)was calculated.The effective targets of D-limonene and 2-Zinol were predicted by Pubchem and SwissTargetPrediction database.GeneCards and OMIM databases were used to search the disease targets associated with candidiasis.Venny software was used to obtain the common target of the two chemical components and candidiasis,and the"Component-Target-disease"network was constructed using Cytoscape 3.9.0 software.Protein interaction PPI network was constructed using STRING database,and GO function and KEGG path enrichment were analyzed using R software.Results:The MIC of D-limonene was 5 mg/mL,and the MIC of 2-Zinol was 2.5 mg/mL.The FIC index of D-limonene combined with 2-Zinol was 0.75,showing additive effect.Network pharmacology screening identified 152 targets related to the two components,893 disease targets,and 24 intersecting targets.Network topology analysis showed that the core targets included tumor necrosis factor(TNF),peroxisome proliferator-activated receptor γ(PPARG)and estrogen receptor(ESR).KEGG analysis showed that the core pathways were C-type lectin receptor signaling pathway and Fc epsilon RI signaling pathway,prolactin signaling pathway and other signaling pathways.Conclusion:Both D-limonene and 2-Zinol have inhibitory effects on Candida albicans,and the combined use of the two components has a certain synergistic effects.Network pharmacological prediction suggests that D-limonene and 2-Zinol may regulate C-type lectin receptor signaling pathway,Fc epsilon RI signaling pathway and other signaling pathways by acting on core targets such as TNF,PPARG and ESR1 to treat candidiasis.
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