Pseudolaric Acid B Combats Drug-Resistant Candida albicans Infection via Dual-Action Mechanisms of Direct Antifungals and Vaginal Microbiota Restoration.

Candidal vaginitis is a prevalent inflammatory condition of the reproductive tract that has a substantial impact on women's health. Conventional antibiotic therapy frequently results in recurrence due to the non-selective elimination of vaginal microbiota and subsequent dysbiosis. In order to overcome this limitation, the focus was directed towards traditional Chinese medicine, which has antimicrobial properties and it was here that pseudolaric acid B (PAB) was identified as a promising active monomer through the utilisation of virtual screening and bioinformatics approaches. In vitro experiments confirmed that PAB inhibits biofilm formation, reduces ergosterol biosynthesis by downregulating the key gene ERG11, and enhances fungal cell membrane permeability, ultimately resulting in fungal cell death. In vivo studies in a mouse model of Candida albicans-induced vaginitis demonstrated that PAB exhibits superior therapeutic efficacy compared to conventional antibiotics. This is characterised by the restoration of normal tissue architecture, a reduction in inflammatory responses and a significant enrichment of beneficial vaginal microbiota as revealed by 16S rRNA sequencing. Collectively, these results highlight PAB as a promising dual-mechanism antifungal agent which acts, at least in part, by disrupting fungal ergosterol biosynthesis and directly eradicating pathogens, while restoring vaginal microecological homeostasis.