Synergistic activity of crocin and crocin loaded in niosomes alone and in combination with fluconazole against Candida albicans isolates: In vitro and in silico study

IF 2.2 4区医学 Q3 MYCOLOGY Journal de mycologie medicale Pub Date : 2024-04-03 DOI:10.1016/j.mycmed.2024.101478

Sara Norozipor , Mehdi Bamorovat , Seyyed Amin Ayatollahi Mosavi , Ehsan Salarkia , Sanaz Hadizadeh , Fatemeh Sharifi , Ali Karamoozian , Mehdi Ranjbar , Setareh Agha Kuchak Afshari

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Abstract

Introduction

Since the drug resistance in Candida species is becoming a serious clinical challenge, novel alternative therapeutic options, particularly herbal medicine, have attracted increasing interest. This study aimed to pinpoint the potential antifungal activity of crocin (Cro), the efficacy of the niosomal formulation of Cro (NCro), and the synergistic activity of both formulations in combination with fluconazole (FLC) against susceptible and resistant C. albicans isolates.

Material and methods

NCro was formulated using the heating method. The in vitro antimycotic activity of Cro, NCro, and FLC was evaluated. Checkerboard and isobologram assays evaluated the interaction between both formulations of Cro and FLC. Necrotic and apoptotic effects of different agents were analyzed using the flow cytometry method. In silico study was performed to examine the interactions between Lanosterol 14 alpha-demethylase and Cro as a part of our screening compounds with antifungal properties.

Results

NCro exhibited high entrapment efficiency up to 99.73 ± 0.54, and the mean size at 5.224 ± 0.618 µm (mean ± SD, n = 3). Both formulations of Cro were shown to display good anticandidal activity against isolates. The synergistic effect of the NCro in combination with FLC is comparable to Cro (P-value =0.03). Apoptotic indicators confirmed that tested compounds caused cell death in isolates. The docking study indicated that Cro has interactivity with the protein residue of 14α-demethylase.

Conclusion

The results showed a remarkable antifungal effect by NCro combined with FLC. Natural compounds, particularly nano-sized carrier systems, can act as an effective therapeutic option for further optimizing fungal infection treatment.

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牛黄素和牛黄素载体与氟康唑单独或联合使用对白色念珠菌分离株的协同活性：体外和硅学研究

导言：由于念珠菌的耐药性正成为严峻的临床挑战，新的替代疗法，尤其是中草药，引起了越来越多的关注。本研究旨在确定巴豆苷（Cro）潜在的抗真菌活性、巴豆苷口服制剂（NCro）的疗效，以及两种制剂与氟康唑（FLC）联合使用对易感和耐药白念珠菌分离株的协同活性。对 Cro、NCro 和 FLC 的体外抗霉菌活性进行了评估。棋盘格法和同分异构法评估了 Cro 和 FLC 两种制剂之间的相互作用。使用流式细胞仪方法分析了不同制剂的坏死和凋亡效应。作为我们筛选具有抗真菌特性的化合物的一部分，我们进行了硅学研究，以检验羊毛甾醇 14 alpha-脱甲基酶与 Cro 之间的相互作用。结果NCro 的夹带效率高达 99.73 ± 0.54，平均尺寸为 5.224 ± 0.618 µm（平均值 ± SD，n = 3）。两种 Cro 制剂都显示出对分离菌具有良好的抗念珠菌活性。NCro 与 FLC 组合的协同效应与 Cro 相当（P 值 =0.03）。细胞凋亡指标证实，受试化合物能导致分离菌的细胞死亡。对接研究表明，Cro 与 14α-demethylase 的蛋白残基有相互作用。天然化合物，尤其是纳米级载体系统，可以作为一种有效的治疗选择，进一步优化真菌感染的治疗。

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.