Dantas-Medeiros Renato, Zanatta Ana Caroline, de Souza Luanda Bárbara Ferreira Canário, Fernandes Júlia Morais, Amorim-Carmo Bruno, Torres-Rêgo Manoela, Fernandes-Pedrosa Matheus de Freitas, Vilegas Wagner, Araújo Thiago Antǒnio de Sousa, Michel Sylvie, Grougnet Raphaël, Chaves Guilherme Maranhão, Zucolotto Silvana Maria
Laboratory of Pharmacognosy, Department of Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Rio Grande do Norte, Natal, Brazil.
Laboratory of Bioprospecting of Natural Products, São Paulo State University (UNESP), São Paulo, Brazil.
Front Microbiol. 2021 Feb 22;12:613155. doi: 10.3389/fmicb.2021.613155. eCollection 2021.
(Burseraceae) is a medicinal plant native to Brazil which is popularly used for treating oral and vaginal infections. There has been no scientific evidence pointing to its efficacy in the treatment of these infections. Thus, this study sought to investigate the cytotoxic, antifungal, and antibiofilm activity of against spp. and to isolate, identify, and quantify the content of B-type oligomeric procyanidins (BDP) in the extract of stem bark. The extract and the -butanol fraction were obtained by maceration and liquid-liquid partition, respectively. Phytochemical analysis performed by HPLC-PDA/ELSD and FIA-ESI-IT-MS/MS allowed the identification and quantification of BDP in the samples. The application of centrifugal partition chromatography helped isolate BDP, which was identified by H NMR and MS analyses. spp. reference strains and clinical isolates (including fluconazole-resistant strains) derived from the blood cultures of candidemic patients and the vaginal secretion of patients with vulvovaginal candidiasis were used for evaluating the antifungal and antibiofilm effects. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were determined by the microdilution technique, and biofilm inhibition was evaluated through crystal violet and XTT assays. The combined action of BDP with fluconazole was determined by the checkerboard method. The extract, the -butanol fraction, and the BDP exhibited antifungal activity with MIC values ranging from 312.5 to 2500 μg/mL and were found to significantly reduce the biofilm formed in all the strains investigated. BDP showed a fungicidal potential against strains of spp. (especially against fluconazole-resistant strains), with MIC and MFC values ranging from 156.2 to 2500 μg/mL. In addition, the combined application of BDP and fluconazole produced synergistic antifungal effects against resistant spp. (FICI = 0.31-1.5). The cytotoxic properties of the samples evaluated in human erythrocytes through hemolytic test did not show hemolytic activity under active concentrations. The findings of the study show that has antifungal and antibiofilm potential but does not cause toxicity in human erythrocytes. Finally, BDP, which was isolated for the first time in , was found to exhibit antifungal effect against spp. either when applied alone or in combination with fluconazole.
（橄榄科）是一种原产于巴西的药用植物，广泛用于治疗口腔和阴道感染。尚无科学证据表明其对这些感染的治疗效果。因此，本研究旨在调查[植物名称]对白色念珠菌的细胞毒性、抗真菌和抗生物膜活性，并分离、鉴定和定量[植物名称]茎皮提取物中B型低聚原花青素（BDP）的含量。提取物和正丁醇部位分别通过浸渍法和液液分配法获得。通过HPLC-PDA/ELSD和FIA-ESI-IT-MS/MS进行的植物化学分析可鉴定和定量样品中的BDP。离心分配色谱法的应用有助于分离BDP，通过1H NMR和MS分析对其进行鉴定。使用白色念珠菌参考菌株和来自念珠菌血症患者血培养及外阴阴道念珠菌病患者阴道分泌物的临床分离株（包括氟康唑耐药菌株）评估抗真菌和抗生物膜效果。采用微量稀释技术测定最低抑菌浓度（MIC）和最低杀菌浓度（MFC），通过结晶紫和XTT试验评估生物膜抑制作用。采用棋盘法测定BDP与氟康唑的联合作用。提取物、正丁醇部位和BDP均表现出抗真菌活性，MIC值范围为312.5至2500μg/mL，并发现能显著减少所有研究的白色念珠菌菌株形成的生物膜。BDP对白色念珠菌菌株（尤其是氟康唑耐药菌株）显示出杀菌潜力，MIC和MFC值范围为156.2至2500μg/mL。此外，BDP与氟康唑联合应用对耐药白色念珠菌产生协同抗真菌作用（FICI = 0.31 - 1.5）。通过溶血试验在人红细胞中评估样品的细胞毒性，在有效浓度下未显示溶血活性。研究结果表明，[植物名称]具有抗真菌和抗生物膜潜力，但对人红细胞无毒性。最后，首次在[植物名称]中分离得到的BDP，无论是单独应用还是与氟康唑联合应用，均对白色念珠菌表现出抗真菌作用。
