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白花丹素,一种植物衍生化合物,对白色念珠菌临床分离株与两性霉素B表现出抗真菌联合效应,并具有抗丙型肝炎病毒活性。

Plumbagin, a Plant-Derived Compound, Exhibits Antifungal Combinatory Effect with Amphotericin B against Candida albicans Clinical Isolates and Anti-hepatitis C Virus Activity.

作者信息

Hassan Sherif T S, Berchová-Bímová Kateřina, Petráš Jan

机构信息

Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tř. 1946/1, 612 42, Brno, Czech Republic.

Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 21 Praha 6 - Suchdol, Prague, Czech Republic.

出版信息

Phytother Res. 2016 Sep;30(9):1487-92. doi: 10.1002/ptr.5650. Epub 2016 May 24.

Abstract

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), the major active constituent of Plumbago indica L., has been shown to be effective against a wide range of infectious microbes. In this study, plumbagin has been evaluated in vitro for its antifungal combinatory effect with amphotericin B against Candida albicans (C. albicans) clinical isolates and anti-hepatitis C virus (HCV) activity. Antifungal activity was determined by broth microdilution method, and combinatory effect was evaluated by checkerboard assay according to ΣFIC indices, while cytotoxicity was determined by MTT assay. Anti-HCV activity was determined in infected Huh7.5 cells using quantitative real-time reverse transcription PCR, and cytotoxicity was evaluated by MTT assay. Plumbagin exerted inhibitory effect against all C. albicans strains with minimum inhibitory concentration values ranging from 7.41 to 11.24 µg/mL. The additive effect of plumbagin when combined with amphotericin B at concentrations of (0.12, 0.13 and 0.19, 1.81 µg/mL, respectively) was obtained against five of seven strains tested with ΣFIC ranging from 0.62 to 0.91. In addition, plumbagin was found to be used safely for topical application when combined with amphotericin B at concentrations corresponding to the additive effect. Plumbagin exerted anti-HCV activity compared with that of telaprevir with IC50 values of 0.57 and 0.01 μM/L, respectively, and selectivity indices SI = 53.7 and SI = 2127, respectively. Our results present plumbagin as a potential therapeutic agent in the treatment of C. albicans and HCV infections. Copyright © 2016 John Wiley & Sons, Ltd.

摘要

白花丹醌(5-羟基-2-甲基-1,4-萘醌)是白花丹的主要活性成分,已被证明对多种传染性微生物有效。在本研究中,对白花丹醌进行了体外评估,考察其与两性霉素B联合抗白色念珠菌临床分离株的抗真菌效果以及抗丙型肝炎病毒(HCV)活性。采用肉汤微量稀释法测定抗真菌活性,根据ΣFIC指数通过棋盘法评估联合效果,同时采用MTT法测定细胞毒性。使用定量实时逆转录PCR在感染的Huh7.5细胞中测定抗HCV活性,并通过MTT法评估细胞毒性。白花丹醌对所有白色念珠菌菌株均有抑制作用,最低抑菌浓度值范围为7.41至11.24μg/mL。白花丹醌与两性霉素B分别以(0.12、0.13和0.19、1.81μg/mL)的浓度联合使用时,对所测试的7株菌株中的5株产生了相加作用,ΣFIC范围为0.62至0.91。此外,发现白花丹醌与两性霉素B以相加作用对应的浓度联合用于局部应用时是安全的。与特拉匹韦相比,白花丹醌具有抗HCV活性,IC50值分别为0.57和0.01μM/L,选择性指数SI分别为53.7和2127。我们的研究结果表明白花丹醌是治疗白色念珠菌和HCV感染的潜在治疗药物。版权所有©2016约翰威立父子有限公司。

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