Zingerone effect against Candida albicans growth and biofilm production

IF 2.2 4区医学 Q3 MYCOLOGY

Journal de mycologie medicale Pub Date : 2024-12-13 DOI:10.1016/j.mycmed.2024.101527

Sayali Chougule , Sargun Basrani , Tanjila Gavandi , Shivani Patil , Shivanand Yankanchi , Ashwini Jadhav , Sankunny Mohan Karuppayil

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引用次数: 0

Abstract

Background

The increasing resistance of Candida albicans biofilms underscores the urgent need for effective antifungals. This study evaluated the efficacy of zingerone and elucidated its mode of action against C. albicans ATCC 90028 and clinical isolate C1.

Experimental Procedure

Minimum inhibitory concentrations (MICs) of zingerone were determined using CLSI methods against planktonic cells, biofilm formation, and yeast-to-hyphal transition. The mode of action was investigated through fluorescent microscopy, ergosterol assays, cell cycle analysis, and RT-PCR for gene expression.

Key Results

Zingerone inhibited planktonic growth and biofilm formation at in C. albicans ATCC 90028 and clinical isolate C1 at 2 mg/mL 4 mg/mL and 1 mg/mL and 2 mg/mL respectively. Treatment with the MIC concentration caused significant cell cycle arrest at the G0/G1 phase, halting proliferation in both the strains. Propidium iodide Staining revealed compromised membrane integrity in both the strains. Also, acridine orange and ethidium bromide dual staining showed increased dead cell proportions in C. albicans ATCC 90028. RT-PCR studies showed downregulation of BCY1, PDE2, EFG1, and upregulation of negative regulators NRG1, TUP1 disrupting growth and virulence pathways. Zingerone induced elevated reactive oxygen species (ROS) levels, triggering apoptosis, evidenced by DNA fragmentation and upregulation of apoptotic markers. It also inhibited ergosterol synthesis in a concentration-dependent manner, crucial for membrane integrity. Importantly, zingerone exhibited minimal hemolytic activity. In an in vivo silkworm model, zingerone demonstrated significant antifungal efficacy, protecting silkworms from infection. It also modulated stress response genes, highlighting its multifaceted action.

Conclusions

In vitro and in vivo findings confirm the potent antifungal efficacy of zingerone against C. albicans ATCC 90028 and clinical isolate C1, suggesting its promising potential as a therapeutic agent that warrants further exploration.

Abstract Image

查看原文本刊更多论文

生姜酮对白色念珠菌生长和生物膜生成的抑制作用。

背景：随着白色念珠菌生物膜耐药性的增加，迫切需要有效的抗真菌药物。本研究评价了生姜酮对白色念珠菌ATCC 90028及临床分离株C1的作用机制。实验步骤：使用CLSI方法测定姜酮对浮游细胞、生物膜形成和酵母-菌丝转化的最低抑制浓度（mic）。通过荧光显微镜、麦角甾醇测定、细胞周期分析和RT-PCR检测基因表达来研究其作用模式。关键结果：生姜酮分别以2 mg/mL、4 mg/mL、1 mg/mL和2 mg/mL浓度抑制白色念珠菌ATCC 90028和临床分离菌C1的浮游生物生长和生物膜形成。MIC浓度处理导致细胞周期阻滞在G0/G1期，两株细胞均停止增殖。碘化丙啶染色显示两种菌株的膜完整性受损。吖啶橙和溴化乙啶双染色显示白色念珠菌ATCC 90028的死细胞比例增加。RT-PCR研究显示BCY1、PDE2、EFG1下调，负调控因子NRG1、TUP1上调，破坏生长和毒力通路。姜酮诱导活性氧（ROS）水平升高，引发细胞凋亡，DNA断裂和凋亡标志物上调证明了这一点。它还以浓度依赖性的方式抑制麦角甾醇的合成，这对膜的完整性至关重要。重要的是，姜酮表现出最小的溶血活性。在家蚕体内模型中，生姜酮显示出明显的抗真菌作用，保护家蚕免受感染。它还调节应激反应基因，突出其多方面的作用。结论：体内外实验结果证实了姜酮对白色念珠菌ATCC 90028和临床分离物C1具有较强的抗真菌作用，提示其作为一种治疗药物的潜力值得进一步探索。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal de mycologie medicale 医学-真菌学

CiteScore

5.10

自引率

2.80%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal de Mycologie Medicale / Journal of Medical Mycology (JMM) publishes in English works dealing with human and animal mycology. The subjects treated are focused in particular on clinical, diagnostic, epidemiological, immunological, medical, pathological, preventive or therapeutic aspects of mycoses. Also covered are basic aspects linked primarily with morphology (electronic and photonic microscopy), physiology, biochemistry, cellular and molecular biology, immunochemistry, genetics, taxonomy or phylogeny of pathogenic or opportunistic fungi and actinomycetes in humans or animals. Studies of natural products showing inhibitory activity against pathogenic fungi cannot be considered without chemical characterization and identification of the compounds responsible for the inhibitory activity. JMM publishes (guest) editorials, original articles, reviews (and minireviews), case reports, technical notes, letters to the editor and information. Only clinical cases with real originality (new species, new clinical present action, new geographical localization, etc.), and fully documented (identification methods, results, etc.), will be considered. Under no circumstances does the journal guarantee publication before the editorial board makes its final decision. The journal is indexed in the main international databases and is accessible worldwide through the ScienceDirect and ClinicalKey platforms.