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评估肉桂醛对新型隐球菌变种的抗真菌活性。

Evaluation of antifungal activity of cinnamaldehyde against Cryptococcus neoformans var. grubii.

机构信息

Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India.

出版信息

Folia Microbiol (Praha). 2020 Dec;65(6):973-987. doi: 10.1007/s12223-020-00806-4. Epub 2020 Jul 2.

DOI:10.1007/s12223-020-00806-4
PMID:32617865
Abstract

Cryptococcosis is a potentially fatal fungal disease which has aggrandized with the emergence of AIDS and antifungal resistance. The currently used antifungals lack the broad-spectrum activity and result in several toxicities during long treatment regimens. Thus, the present study aims to evaluate the antifungal activity of cinnamaldehyde against Cryptococcus neoformans var. grubii, the etiological agent of the disease. Quantitative and qualitative in vitro fungal susceptibilities were carried out by minimum inhibitory concentration assay, flow cytometric analysis, and confocal microscopy. Micromorphological alterations were studied through scanning electron and light microscopies. "In vivo" antifungal efficacy of cinnamaldehyde was assessed. Cinnamaldehyde showed antifungal activity against C. neoformans in a dose-dependent manner. A concentration of 1.37 mg/mL of cinnamaldehyde was found to be inhibitory and fungicidal while the low concentration (0.68 mg/mL) was found to induce micromorphological changes and formation of giant/titan-like cells in this pathogen. The reparative activity of cinnamaldehyde and its ability to prolong the life even after the advent of cryptococcal meningitis in mice was also noticed. This study suggests potent anti-cryptococcal activity of cinnamaldehyde. Though, it has a couple of limitations like allergy and low bioavailability. However, these problems can be circumvented by developing suitable analogs of the compound. It, therefore, could be used as a therapeutic option against cryptococcosis and cryptococcal meningitis. Moreover, the evaluation of its pharmacokinetic and pharmacodynamic properties is desirable.

摘要

隐球菌病是一种潜在致命的真菌感染病,随着艾滋病和抗真菌药物耐药性的出现而加剧。目前使用的抗真菌药物缺乏广谱活性,并且在长期治疗方案中会导致多种毒性。因此,本研究旨在评估肉桂醛对新型隐球菌变种格氏变种的抗真菌活性,该变种是该疾病的病原体。通过最小抑菌浓度测定、流式细胞术分析和共聚焦显微镜对定量和定性的体外真菌药敏性进行评估。通过扫描电子显微镜和光学显微镜研究微观形态变化。评估肉桂醛的“体内”抗真菌功效。肉桂醛对新型隐球菌呈剂量依赖性抗真菌活性。发现 1.37mg/mL 的肉桂醛浓度具有抑制和杀菌作用,而低浓度(0.68mg/mL)则发现可诱导该病原体的微观形态变化和形成巨大/泰坦样细胞。还注意到肉桂醛的修复活性及其在小鼠出现隐球菌性脑膜炎后延长生命的能力。这项研究表明肉桂醛具有很强的抗隐球菌活性。尽管它有一些局限性,如过敏和低生物利用度。然而,通过开发该化合物的合适类似物可以规避这些问题。因此,它可以作为治疗隐球菌病和隐球菌性脑膜炎的一种选择。此外,还需要评估其药代动力学和药效动力学特性。

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本文引用的文献

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PLoS Pathog. 2018 May 18;14(5):e1006982. doi: 10.1371/journal.ppat.1006982. eCollection 2018 May.
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Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals.新型隐球菌在体外可响应多种信号形成类似泰坦的细胞。
PLoS Pathog. 2018 May 18;14(5):e1007007. doi: 10.1371/journal.ppat.1007007. eCollection 2018 May.
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The Cryptococcus neoformans Titan cell is an inducible and regulated morphotype underlying pathogenesis.
新型隐球菌泰坦细胞是一种诱导和调节的形态,是发病机制的基础。
PLoS Pathog. 2018 May 18;14(5):e1006978. doi: 10.1371/journal.ppat.1006978. eCollection 2018 May.
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Mechanisms of -Mediated Host Damage.-Mediated 宿主损伤的机制。
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Antifungal and Anti-Biofilm Activity of Essential Oil Active Components against and .精油活性成分对……的抗真菌和抗生物膜活性
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Med Mycol. 2017 Nov 1;55(8):820-827. doi: 10.1093/mmy/myx001.
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