Antifungal Activity of the Dichloromethane Extract of CaoHuangGuiXiang Formula Against by in vitro and in vivo Evaluation.

PURPOSE

CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of -related infection. However, its antifungal mechanisms against the emerging fungal pathogen remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against .

METHODS

The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against , including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a infection model.

RESULTS

First, 20 major compounds in CHGX-DME were detected and characterized. The MIC and MIC of CHGX-DME against isolates ranged from 50-200 mg/L and 100-400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in . Importantly, it significantly improved the survival rate and reduced the fungal burden in infection models, suggesting a remarkable treatment effect against infection.

CONCLUSION

CHGX-DME exhibited potent antifungal activity against and significantly ameliorated this fungal infection in the model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen .