The Anti-Biofilm Efficacy of Caffeic Acid Phenethyl Ester (CAPE) In Vitro and a Murine Model of Oral Candidiasis.
The Anti-Biofilm Efficacy of Caffeic Acid Phenethyl Ester (CAPE) In Vitro and a Murine Model of Oral Candidiasis.
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DOI：
10.3389/fcimb.2021.700305
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发表时间：
2021
影响因子：
5.7
通讯作者：
Junqueira JC
中科院分区：
文献类型：
--
作者：
de Barros PP;Rossoni RD;Garcia MT;Kaminski VL;Loures FV;Fuchs BB;Mylonakis E;Junqueira JC
白色念珠菌是口腔念珠菌病的主要致病菌。目前，这些感染的治疗选择受到抗真菌药物的不良反应和耐药菌株的出现的限制。因此，需要开发新的抗真菌药物来预防和治疗口腔念珠菌感染。咖啡酸苯乙酯（CAPE）是一种天然多酚类化合物，具有多种药理学性质。在这项研究中，我们研究了CAPE是否可以对口腔念珠菌病具有抗真菌和免疫调节作用。使用最小抑菌浓度（MIC）测定进行评估CAPE的抗真菌活性的初步测试，该测定证明抑制范围为16至32 μg/mL，证实其对几种念珠菌的抗真菌活性。从口腔分离的白色念珠菌菌株。随后，我们分析了体外形成的念珠菌属生物膜，其中与未处理的生物膜相比，在5x MIC下的CAPE处理导致总生物量减少68.5%，活细胞计数（CFU/mL）减少约2.60 Log（p<0.0001）。接下来，从未处理的和CAPE处理的生物膜中提取RNA，并通过实时qPCR进行分析。与未处理的对照组相比，CAPE下调了一系列分析的基因（ALS 1、ECE 1、EPA 1、HWP 1、YWP 1、BCR 1、BGR 1、CPH 1、EFG 1、NDT 80、ROB 1、TEC 1、UME 6、SAP 2、SAP 5、PBL 2和LIP 9）（p<0.0001）。在使用Galleria mellonella的体内研究中，用CAPE处理延长了被C.白念珠菌感染率为44.5%（P < 0.05），血细胞数增加2.07倍。流式细胞术显示最显著的增加是P2和P3型血细胞，颗粒细胞，吞噬病原体。此外，CAPE处理降低了血淋巴中的真菌负荷，并刺激了抗真菌肽基因如加利霉素和加利霉素的表达。G.在小鼠口腔念珠菌病模型中，CAPE降低了C.白色念珠菌定植（~2 log CFU/mL）。此外，CAPE治疗显著减少了假膜性病变、上皮表面上的菌丝侵入、组织损伤和炎性浸润（p < 0.05）。与感染和未处理组相比，CAPE还能够将β-防御素3的表达增加3.91倍（p < 0.0001）。总之，这些结果表明，CAPE具有抗真菌和免疫调节作用，使其成为一种有前途的天然抗真菌剂，用于治疗和预防念珠菌病，并显示出对口腔念珠菌病的影响。
Candida albicans is the main fungal species associated with the development of oral candidiasis. Currently, therapeutic options for these infections are limited by the adverse effects of antifungal drugs and by the emergence of drug resistant strains. Thus, the development of new antifungal agents is needed for the prevention and treatment of oral Candida infections. Caffeic acid phenethyl ester (CAPE) is a natural compound from propolis polyphenolic groups that exhibits many pharmacological properties. In this study, we investigated whether CAPE can have antifungal and immunomodulatory effects on oral candidiasis. Preliminary tests to assess the antifungal activity of CAPE were performed using the Minimum Inhibitory Concentration (MIC) assay that demonstrated inhibition in a range from 16 to 32 μg/mL, confirming its antifungal activity on several C. albicans strains isolated from the oral cavity. Subsequently, we analyzed Candida spp biofilms formed in vitro, in which CAPE treatment at 5 x MIC caused a reduction of 68.5% in the total biomass and ~2.60 Log in the viable cell count (CFU/mL) in relation to the untreated biofilm (p<0.0001). Next, RNA was extracted from untreated and CAPE-treated biofilms and analyzed by real-time qPCR. A series of genes analyzed (ALS1, ECE1, EPA1, HWP1, YWP1, BCR1, BGR1, CPH1, EFG1, NDT80, ROB1, TEC1, UME6, SAP2, SAP5, PBL2, and LIP9) were downregulated by CAPE compared to the untreated control group (p<0.0001). In in vivo studies using Galleria mellonella, the treatment with CAPE prolonged survival of larvae infected by C. albicans by 44.5% (p < 0.05) and accompanied by a 2.07-fold increase in the number of hemocytes. Flow cytometry revealed the most prominent increases were in types P2 and P3 hemocytes, granular cells, which phagocytize pathogens. In addition, CAPE treatment decreased the fungal load in the hemolymph and stimulated the expression of antifungal peptide genes such as galiomicin and gallerimycin. The antifungal and immunomodulatory activities observed in G. mellonella were extended to a murine model of oral candidiasis, in which CAPE decreased the levels of C. albicans colonization (~2 log CFU/mL) in relation to the untreated control group. In addition, CAPE treatment significantly reduced pseudomembranous lesions, invasion of hyphae on epithelium surfaces, tissue damage and inflammatory infiltrate (p < 0.05). CAPE was also able to increase the expression of β-defensin 3 compared to the infected and untreated group by 3.91-fold (p < 0.0001). Taken together, these results show that CAPE has both antifungal and immunomodulatory effects, making it a promising natural antifungal agent for the treatment and prevention of candidiasis and shows impact to oral candidiasis.
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DOI：
10.1155/2021/1059274
发表时间：
2021
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Ferreira EDS;Rosalen PL;Benso B;de Cássia Orlandi Sardi J;Denny C;Alves de Sousa S;Queiroga Sarmento Guerra F;de Oliveira Lima E;Almeida Freires I;Dias de Castro R
通讯作者：
Dias de Castro R
影响因子：
3.3
作者：
de Barros, Patricia Pimentel;Rossoni, Rodnei Dennis;Cardoso Jorge, Antonio Olavo
通讯作者：
Cardoso Jorge, Antonio Olavo
影响因子：
3.3
作者：
Jordao, Claudia Carolina;Klein, Marlise Inez;Pavarina, Ana Claudia
通讯作者：
Pavarina, Ana Claudia
影响因子：
2.8
作者：
Granger, BL;Flenniken, ML;Cutler, JE
通讯作者：
Cutler, JE
影响因子：
5.5
作者：
de Barros, Patricia Pimentel;Rossoni, Rodnei Dennis;Cardoso Jorge, Antonio Olavo
通讯作者：
Cardoso Jorge, Antonio Olavo