Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun 130041, China.
Department of Rehabilitation Medicine, The Second Hospital of Jilin University, Changchun 130041, China.
Biomed Pharmacother. 2024 Oct;179:117352. doi: 10.1016/j.biopha.2024.117352. Epub 2024 Aug 28.
The fungus Candida albicans causes various kinds of human infections, including oral thrush, vulvovaginitis and life-endangering bloodstream infections, the incidence of which are rising. Worsening this, the clinical antifungals are limited to a few, highlighting the necessity to develop novel antifungal therapies. In this study, the antifungal activities of isobavachalcone against C. albicans SC5314 and nine C. albicans clinical isolates were tested. The effects of isobavachalcone (IBC) on C. albicans virulence factors, such as hyphal formation, adhesion, biofilm formation and extracellular phospholipase production, as well as the underlying mechanism, were also evaluated. Antifungal susceptibility test revealed that IBC has significant anti-Candida activities, with both MIC and MFC being 4-5 μg/mL against all strains tested. Hyphal formation in RPMI-1640, Spider and GlcNAc medium, adhesion to abiotic polystyrene surfaces and surfaces of A549 cells, could be inhibited by IBC. Most important, IBC could inhibit the C. albicans biofilm formation and development. PI staining tests showed that IBC could increase the cell membrane permeability, suggesting the damages to the fungal cell membrane. IBC was further demonstrated to induce excessive ROS production in C. albicans planktonic cells and its mature biofilms, as revealed by DCFH fluorescence detection through flowcytometry and relative fluorescence intensity analysis (with a microplate reader). The roles of ROS in the antifungal activity of IBC were further confirmed through antioxidant rescue assays in MIC and biofilm formation tests. Compared to its antifungal activity, the cytotoxicity against mammalian cells was low, indicating its potential in developing antifungal therapies.
白色念珠菌会引起各种人类感染，包括口腔鹅口疮、阴道外阴念珠菌病和危及生命的血流感染，其发病率正在上升。更糟糕的是，临床用抗真菌药物仅限于少数几种，这凸显了开发新型抗真菌疗法的必要性。在这项研究中，检测了异甘草素（IBC）对白色念珠菌 SC5314 和 9 株白色念珠菌临床分离株的抗真菌活性。还评估了 IBC 对白色念珠菌毒力因子（如菌丝形成、黏附、生物膜形成和细胞外磷脂酶产生）的影响及其潜在机制。抗真菌药敏试验显示，IBC 对所有受试菌株均具有显著的抗真菌活性，MIC 和 MFC 均为 4-5μg/mL。在 RPMI-1640、蜘蛛和 GlcNAc 培养基中，菌丝形成、非生物聚苯乙烯表面和 A549 细胞表面的黏附可以被 IBC 抑制。最重要的是，IBC 可以抑制白色念珠菌生物膜的形成和发展。PI 染色试验表明，IBC 可以增加细胞膜通透性，提示真菌细胞膜受损。通过流式细胞术和相对荧光强度分析（使用微孔板读数器）检测 DCFH 荧光，进一步证明 IBC 可以诱导白色念珠菌浮游细胞及其成熟生物膜中过量的 ROS 产生。通过 MIC 和生物膜形成试验中的抗氧化剂挽救实验进一步证实了 ROS 在 IBC 抗真菌活性中的作用。与抗真菌活性相比，对哺乳动物细胞的细胞毒性较低，表明其在开发抗真菌疗法方面具有潜力。
