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Spilanthol as a promising antifungal alkylamide for the treatment of vulvovaginal candidiasis
Medical Mycology ( IF 2.7 ) Pub Date : 2021-09-01 , DOI: 10.1093/mmy/myab054
Rodrigo L Fabri 1 , Jhamine C O Freitas 1 , Ari S O Lemos 1 , Lara M Campos 1 , Irley O M Diniz 1 , Nícolas C C Pinto 1 , Thiago P Silva 2 , Cinthia Palazzi 2 , Paula Marchesini 3 , Caio Monteiro 4 , Alan F Barbosa 5 , Mário G Carvalho 6 , Luciana M Chedier 7 , Marcelo G F Araújo 8 , Ana Carolina M Apolônio 9 , Vinícius N Rocha 10 , Rossana C N Melo 2 , Priscila F Pinto 1
Affiliation  

Spilanthol is a bioactive alkylamide from the native Amazon plant species, Acmella oleracea. However, antifungal activities of spilanthol and its application to the therapeutic treatment of candidiasis remain to be explored. This study sought to evaluate the in vitro and in vivo antifungal activity of spilanthol previously isolated from A. oleracea (spilanthol(AcO)) against Candida albicans ATCC® 10231™, a multidrug-resistant fungal strain. Microdilution methods were used to determine inhibitory and fungicidal concentrations of spilanthol(AcO). In planktonic cultures, the fungal growth kinetics, yeast cell metabolic activity, cell membrane permeability and cell wall integrity were investigated. The effect of spilanthol(AcO) on the proliferation and adhesion of fungal biofilms was evaluated by whole slide imaging and scanning electron microscopy. The biochemical composition of the biofilm matrix was also analyzed. In parallel, spilanthol(AcO) was tested in vivo in an experimental vulvovaginal candidiasis model. Our in vitro analyses in C. albicans planktonic cultures detected a significant inhibitory effect of spilanthol(AcO), which affects both yeast cell membrane and cell wall integrity, interfering with the fungus growth. C. albicans biofilm proliferation and adhesion, as well as, carbohydrates and DNA in biofilm matrix were reduced after spilanthol(AcO) treatment. Moreover, infected rats treated with spilanthol(AcO) showed consistent reduction of both fungal burden and inflammatory processes compared to the untreated animals. Altogether, our findings demonstrated that spilanthol(AcO) is an bioactive compound against planktonic and biofilm forms of a multidrug resistant C. albicans strain. Furthermore, spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans. Lay summary This study sought to evaluate the antifungal activity of spilanthol against Candida albicans ATCC® 10 231™, a multidrug-resistant fungal strain. Our findings demonstrated that spilanthol(AcO) can be potentially considered for therapeutical treatment of vulvovaginal candidiasis caused by C. albicans.

中文翻译:


千日菊素作为一种有前景的抗真菌烷基酰胺用于治疗外阴阴道念珠菌病



千日菊素是一种来自亚马逊本土植物 Acmella oleracea 的生物活性烷基酰胺。然而,千日菊素的抗真菌活性及其在念珠菌病治疗中的应用仍有待探索。本研究旨在评估先前从甘蓝中分离出的千日菊素(千日菊素(AcO))对多重耐药真菌菌株白色念珠菌 ATCC® 10231™ 的体外和体内抗真菌活性。采用微量稀释法测定千日菊素(AcO)的抑制浓度和杀菌浓度。在浮游培养中,研究了真菌生长动力学、酵母细胞代谢活性、细胞膜通透性和细胞壁完整性。通过全玻片成像和扫描电镜评估千日菊素(AcO)对真菌生物膜增殖和粘附的影响。还分析了生物膜基质的生化成分。同时,在实验性外阴阴道念珠菌病模型中对千日菊素 (AcO) 进行了体内测试。我们对白色念珠菌浮游培养物的体外分析检测到千日菊素 (AcO) 具有显着的抑制作用,它会影响酵母细胞膜和细胞壁的完整性,从而干扰真菌生长。千日菊素(AcO)处理后,白色念珠菌生物膜增殖和粘附以及生物膜基质中的碳水化合物和DNA减少。此外,与未治疗的动物相比,用千日菊素(AcO)治疗的感染大鼠显示出真菌负荷和炎症过程的持续减少。总而言之,我们的研究结果表明,千日菊素 (AcO) 是一种针对浮游和生物膜形式的多重耐药白色念珠菌菌株的生物活性化合物。 此外,千日菊素(AcO)可潜在地考虑用于治疗由白色念珠菌引起的外阴阴道念珠菌病。本研究旨在评估千日菊素对白色念珠菌 ATCC® 10 231™(一种多重耐药真菌菌株)的抗真菌活性。我们的研究结果表明,千日菊素 (AcO) 可潜在地考虑用于治疗由白色念珠菌引起的外阴阴道念珠菌病。
更新日期:2021-09-01
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