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氟康唑和蛇床子素联合抗氟康唑耐药白念珠菌的强效协同作用。

Potent Synergism of Fluconazole and Osthole against Fluconazole-Resistant Candida albicans.

机构信息

Clinical Pharmacy Center, Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.

New Drug Research and Development Center, School of Pharmacy, Second Military Medical University, Shanghai, China.

出版信息

Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.00436-17. Print 2017 Aug.

Abstract

Osthole is a natural coumarin that exhibits wide biological and pharmacological activities such as neuroprotective, osteogenic, immunomodulation, antitumor, and anti-inflammatory effects. In this study, we investigated the antifungal effects of osthole A checkerboard microdilution assay showed that osthole has significant synergistic effect with fluconazole against fluconazole-resistant Similar results were obtained from a growth curve assay. Meanwhile, XTT reduction assay demonstrated the synergism of fluconazole and osthole against biofilm formation. Microarray results showed that the expression of genes involved in the oxidation-reduction process, energy metabolism, and transportation changed significantly after the combined treatment with fluconazole and osthole, and further results showed that endogenous reactive oxygen species (ROS) was significantly increased in the combination group. In conclusion, these results demonstrate the synergism of fluconazole and osthole against fluconazole-resistant and indicate that endogenous ROS augmentation might contribute to the synergism of fluconazole and osthole.

摘要

蛇床子素是一种天然香豆素,具有广泛的生物学和药理学活性,如神经保护、成骨、免疫调节、抗肿瘤和抗炎作用。在这项研究中,我们研究了蛇床子素的抗真菌作用。棋盘微量稀释试验表明,蛇床子素与氟康唑对氟康唑耐药有显著的协同作用。从生长曲线试验中也得到了类似的结果。同时,XTT 还原试验表明氟康唑和蛇床子素对生物膜形成有协同作用。微阵列结果显示,氟康唑和蛇床子素联合处理后,与氧化还原过程、能量代谢和运输相关的基因表达显著改变,进一步的结果表明,组合组中内源性活性氧(ROS)显著增加。总之,这些结果表明氟康唑和蛇床子素对氟康唑耐药有协同作用,并表明内源性 ROS 增加可能有助于氟康唑和蛇床子素的协同作用。

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