ETHNOPHARMACOLOGICAL RELEVANCETraditional Chinese medicine (TCM) compound preparations play a significant role in the clinical treatment of vulvovaginal candidiasis (VVC).AIM OF THE STUDYCandida albicans (CA) is an opportunistic fungal pathogen responsible for various human diseases, including vulvovaginal candidiasis (VVC). Hyphal growth and biofilm formation are critical virulence factors contributing to CA's pathogenicity and drug resistance. ICAM, a topical TCM compound preparation developed by our laboratory, was investigated for its chemical component, antifungal mechanisms against CA and therapeutic efficacy against VVC.MATERIALS AND METHODSThe main components of ICAM were analyzed using the Gas Chromatography-Mass Spectrometry (GC-MS) method. To elucidate the mechanisms underlying ICAM's antifungal activity, we combined phenotypic assays, transcriptomic and proteomic analyses. The therapeutic potential of ICAM for VVC and its irritancy to vaginal tissue were evaluated using cavity model experiments.RESULTSICAM contained a diverse range of phenolic compounds, such as phenol, 2-methoxyphenol, and 4-ethyl-2-methoxyphenol, among others. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of ICAM against CA were 2.50% and 10.00% for the standard strain, and 5.00% and 20.00% for the clinical strain, respectively. At 1.25%, ICAM significantly inhibited CA adherence, hyphal growth, and biofilm formation, while also reducing surface hydrophobicity and exopolysaccharide production. Treatment with 10.00% ICAM completely disrupted CA membrane integrity. Transcriptome analysis revealed that multiple genes associated with biofilm and hyphal formation, including five MAPK signaling pathway genes (Ras1, Cdc24, Ste11, Cek1, Hst7), four hyphae-specific genes (Hgc1, Hwp1, Ece1, Als3), and three additional genes (Tec1, Csh1, Pmt1), were significantly downregulated. Additionally, proteins associated with the MAPK signaling pathway, including the 14-3-3 domain-containing protein, cell wall protein RTB1, Msb2p, Ras family protein, and RhoGAP domain family protein, were significantly downregulated. These findings suggest that the MAPK signaling pathway plays a crucial role in mediating ICAM's inhibition of hyphal growth and biofilm formation in CA. In vivo, 10.00% ICAM completely eliminated the symptoms of CA infection. The vaginal fungal burden in the 20.00% and 40.00% ICAM groups was reduced to zero after 12 days of treatment. Furthermore, 40.00% ICAM significantly reduced lactate dehydrogenase and inflammatory cytokine levels, demonstrating efficacy comparable to the positive control. ICAM demonstrated excellent mucosal compatibility in the cavity experiment.CONCLUSIONSThese findings highlight the potential of ICAM as a novel antifungal agent for the treatment of VVC.
