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Cao Huang Gui Xiang (CHGX) formula, a Chinese herbal medicine, has been empirically used for the treatment of  Candida  infections. In the present study, we discovered that the CHGX showed potent antifungal activities against the major human fungal pathogen  Candida albicans  and other clinical  Candida  species. Besides, we indicated that CHGX had  in vivo  efficacy on treating  C. albicans  infection in mice without noticeable toxicity at the clinical therapeutic concentration. We then set out to investigate the antifungal mechanisms of CHGX against  C. albicans . We found that CHGX played an important role in inhibiting biofilm formation and filament development, two critical virulence factors of  C. albicans . We further demonstrated that CHGX disrupted cell membrane integrity, triggered the accumulation of reactive oxygen species (ROS) and consumption of adenosine triphosphate (ATP), followed by a rapid fungal cell death in  C. albicans . Multiple pathways, including the conserved Ras1-cAMP pathway and mitochondrial protein Mcu1 are involved in CHGX-induced cell death. Our finding expands the understanding of antifungal mechanism of CHGX against  C. albicans , and provides new insights in treating patients with  Candida  infections in clinical practice.

Antifungal Mechanisms of a Chinese Herbal Medicine, Cao Huang Gui Xiang, Against Candida Species