Identification of Ermiao Fang Jiawei extract as potential synergist against fluconazole-resistant Candida albicans in vitro and in a vulvovaginal candidiasis model

Song J, Cheng X, Gao J, Liang Z, Xue H, Zhao H · Natural Product Research · 2025 November 10

DOI 10.1080/14786419.2025.2583348

Objective

To investigate the synergistic effect of Eth-EMFJ in combination with FCZ on FCZ-resistant Candida albicans in the treatment of vulvovaginal candidiasis.

Conclusions

The combination of Eth-EMFJ and FCZ showed a synergistic effect in inhibiting the growth, adherence, and biofilm formation of FCZ-resistant C. albicans, potentially through alterations in glycolysis, cell wall, and drug resistance genes, ultimately offering a promising therapeutic approach for managing VVC caused by FCZ-resistant strains.

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Insights

The combined application of Eth-EMFJ and Fluconazole may potentially provide an effective therapy for managing vulvovaginal candidiasis resistant to Fluconazole.

This study leverages UHPLC-MS/MS technology to define the key components of Ermiao Fang Jiawei's ethanolic extract (Eth-EMFJ). Identified components include atractylodin, berberine, osthole, gallic acid, and ellagic acid. These components exhibit a synergistic effect when combined with Fluconazole (FCZ) as observed from FICI values being ≤0.5. EMFJ/FCZ interaction not only inhibits the growth and adherence of FCZ-resistant cells but also reduces their hydrophobicity, hyphal development, and biofilm formation. In the course of the investigation, RNA-sequencing helped reveal alterations in genes associated with glycolysis, cell wall structure, and drug resistance, which implies their potential involvement in the synergy of Eth-EMFJ and FCZ. Additionally, the treatment of Eth-EMFJ/FCZ had a protective effect against fungal colonisation, irritation, and allowed for the restoration of keratinization in vaginal mucosa.