AUTHOR=Yue Huizhen , Xu Xiaolong , He Shasha , Cui Xuran , Guo Yuhong , Zhao Jingxia , Peng Bing , Liu Qingquan 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.813818

DOI=10.3389/fphar.2022.813818

ISSN=1663-9812

ABSTRACT=<p>Cao Huang Gui Xiang (CHGX) formula, a Chinese herbal medicine, has been empirically used for the treatment of <italic>Candida</italic> infections. In the present study, we discovered that the CHGX showed potent antifungal activities against the major human fungal pathogen <italic>Candida albicans</italic> and other clinical <italic>Candida</italic> species. Besides, we indicated that CHGX had <italic>in vivo</italic> efficacy on treating <italic>C. albicans</italic> infection in mice without noticeable toxicity at the clinical therapeutic concentration. We then set out to investigate the antifungal mechanisms of CHGX against <italic>C. albicans</italic>. We found that CHGX played an important role in inhibiting biofilm formation and filament development, two critical virulence factors of <italic>C. albicans</italic>. 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 <italic>C. albicans</italic>. 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 <italic>C. albicans</italic>, and provides new insights in treating patients with <italic>Candida</italic> infections in clinical practice.</p>