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黄酮类、黄酮醇类及糖基化衍生物——对生长、毒力、[具体基因1]和[具体基因2]表达以及细胞毒性的影响

Flavones, Flavonols, and Glycosylated Derivatives-Impact on Growth and Virulence, Expression of and , Cytotoxicity.

作者信息

Ivanov Marija, Kannan Abhilash, Stojković Dejan S, Glamočlija Jasmina, Calhelha Ricardo C, Ferreira Isabel C F R, Sanglard Dominique, Soković Marina

机构信息

Department of Plant Physiology, Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11000 Belgrade, Serbia.

Institute of Microbiology, University Hospital Lausanne and University Hospital Center, Rue du Bugnon 48, 1011 Lausanne, Switzerland.

出版信息

Pharmaceuticals (Basel). 2020 Dec 30;14(1):27. doi: 10.3390/ph14010027.

Abstract

Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and apigetrin) along with their impact on genes encoding efflux pumps () and ergosterol biosynthesis enzyme () has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, apigetrin, and quercitrin has downregulated . Contrary to rutin and apigenin, isoquercitrin has upregulated . Except apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and apigetrin; these results indicate flavonoids' indispensable capacity for further development as part of an anticandidal therapy or prevention strategy.

摘要

由于全球真菌感染的高发病率,对新型治疗方法的开发需求日益增加。多种天然产物已得到广泛研究,其中黄酮类化合物备受关注。本研究的主题是选定的黄酮(木犀草素、芹菜素)、黄酮醇(槲皮素)及其糖基化衍生物(槲皮苷、异槲皮苷、芦丁和芹菜苷)的抗真菌能力,以及它们对编码外排泵()和麦角固醇生物合成酶()的基因的影响。还探讨了黄酮类化合物对原代肝细胞的细胞毒性。木犀草素、槲皮苷、异槲皮苷和芦丁抑制了的生长,最低抑菌浓度为37.5 µg/mL。异槲皮苷的应用使生物膜形成能力降低了76%,并抑制了酵母的菌丝形成。用芹菜素、芹菜苷和槲皮苷进行体外处理可下调。与芦丁和芹菜素相反,异槲皮苷上调了。除芹菜苷和槲皮苷(分别为90 µg/mL和73 µg/mL时抑制50%的净细胞生长)外,所检测的黄酮类化合物均未表现出细胞毒性。芹菜素和芹菜苷对真菌毒力和抗真菌耐药相关基因表达的降低最为明显;这些结果表明黄酮类化合物作为抗念珠菌治疗或预防策略的一部分,具有进一步开发的不可或缺的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7abc/7824033/30a6be064526/pharmaceuticals-14-00027-g001.jpg

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