Exploring the therapeutic effects of Pulsatilla Decoction on Vulvovaginal candidiasis through the IL-23/IL-17 axis based on network pharmacology and animal experiments
OBJECTIVE To explore the therapeutic effects and mechanism of Pulsatilla Decoction on Vulvovaginal candidia-sis(VVC)based upon network pharmacology and animal experiments.METHODS The active ingredients and corresponding targets of Pulsatilla Decoction were collected through literature reviews and searching the database of TCMSP.Gene Cards was applied for obtaining the potential targets related to VVC and Cytoscape 3.6.0 for constructing the network of"drug active components-targets-pathways".And the database of String was utilized for constructing a protein interaction network.Gene ontol-ogy(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed by the platform of DAVID.Molecular docking was performed with AutoDock software.Specific pathogen free Kunming(SPF-KM)mice were ran-domized into six groups of normal,model,low/medium/high-dose Pulsatilla Decoction and fluconazole.VVC model was estab-lished through an inoculation of Candida albicans.All groups were continuously dosed for 14 days.Fungal quantities in vaginal lavage fluid were determined by Gram stain and plate counting.Hematoxylin-eosin(HE)stain was utilized for observing the mor-phology of vaginal tissue.Enzyme-linked immunosorbent assay(ELISA)was employed for detecting the serum contents of IL-17,IL-23 and IL-1β.The expressions of core regulatory factors,including TNF-α,STAT3,HSP90,ESR and key regulator ROR-γT protein in IL-23/IL-17 axis were measured by Western blot.RESULTS Through network pharmacology screening,the core components identified for treating VVC included anemoside B4,dihydroniloticin,obacunone,β-sitosterol and berberine.Additionally,18 key target proteins and 75 pathways were identified as crucial for therapeutic effects for VVC.As compared with model group,a treatment of Pulsatilla Decoction could significantly lower both fungal burden in vagina and serum levels of IL-17,IL-23 and IL-1β.Moreover,the protein expression levels of TNF-α,STAT3,HSP90,ESR and ROR-γT dropped in vaginal tissue(P＜0.05).CONCLUSION Pulsatilla Decoction exerts its therapeutic effects on VVC through modulating the targets of STAT3 and TNF-α and regulating the axis of IL-23/IL-17.
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