Department of Restorative Sciences, Faculty of Dentistry, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait.
Department of Bioclinical Sciences, Faculty of Dentistry, Health Sciences Center, Kuwait University, P.O. Box 24923, Safat, 13110, Kuwait; Environment and Life Sciences Research Center, Kuwait Institute for Scientific Research, P. O. Box 24885, 13109 Safat, Kuwait.
Microb Pathog. 2017 Dec;113:209-217. doi: 10.1016/j.micpath.2017.10.040. Epub 2017 Oct 23.
The incidence of oral candidosis has increased in recent years due to the escalation in HIV-infection, cancer treatments, organ transplantation, and diabetes. In addition, corticosteroid use, dentures, and broad-spectrum antibiotic use have also contributed to the problem. Treatment of oral candidosis has continued to be problematic because of the potential toxicity of antifungals in clinical use, and, above all, development of drug resistance among patients. In this study, the antifungal effect of magnolol was investigated against 64 strains of Candida spp. (four standard and 60 oral isolates) through minimum inhibitory concentration (MIC) and growth curve assays. Insight into the mechanisms of the antifungal action has been gained through ultrastructural studies using confocal scanning laser microscopy (CSLM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Molecular docking was done for predicting the interactions of magnolol with ergosterol at supramolecular level. The toxicity of magnolol on human erythrocytes was measured by in vitro hemolytic assay. MIC values of magnolol ranged from 16-64 μg/ml, respectively. All tested isolates showed a marked sensitivity towards magnolol in growth curve assays. Biofilm results suggested that magnolol showed strong anti-biofilm activity. The results obtained for four different Candida spp. demonstrated that MBIC values of magnolol showed the average biofilm inhibition by 69.5%, respectively. CLSM experiments showed that cells exposed to magnolol (MIC) exhibited cell membrane disruption. SEM analysis of magnolol treated cells resulted in deformed cells. TEM micrographs showed rupturing of the cell wall and plasma membrane, releasing the intracellular content, and swelling of the cell wall. Hemolytic activity of magnolol is 11.9% at its highest MIC compared to an activity level of 25.4% shown by amphotericin B (Amp B) at 1 μg/ml. Lipinski's parameters calculated for magnolol suggested its good oral bioavailability. Docking studies indicated that magnolol might be interacting with ergosterol in the fungal cell membranes. Together, the present study provides enough evidence for further work on magnolol so that better strategies could be employed to treat oral candidosis.
近年来，由于 HIV 感染、癌症治疗、器官移植和糖尿病的增加，口腔念珠菌病的发病率有所上升。此外，皮质类固醇的使用、义齿和广谱抗生素的使用也导致了这个问题。由于临床使用的抗真菌药物的潜在毒性，以及患者中药物耐药性的发展，口腔念珠菌病的治疗仍然存在问题。在这项研究中，通过最低抑菌浓度（MIC）和生长曲线测定法，研究了厚朴酚对 64 株念珠菌属（4 株标准株和 60 株口腔分离株）的抗真菌作用。通过共聚焦扫描激光显微镜（CSLM）、扫描电子显微镜（SEM）和透射电子显微镜（TEM）的超微结构研究，深入了解了抗真菌作用的机制。通过分子对接预测了厚朴酚与麦角甾醇在超分子水平上的相互作用。通过体外溶血试验测定了厚朴酚对人红细胞的毒性。厚朴酚的 MIC 值分别为 16-64μg/ml。所有测试的分离株在生长曲线测定中对厚朴酚表现出明显的敏感性。生物膜结果表明，厚朴酚具有很强的抗生物膜活性。对四种不同念珠菌属的研究结果表明，厚朴酚的 MBIC 值分别平均抑制生物膜 69.5%。CLSM 实验表明，暴露于厚朴酚（MIC）的细胞表现出细胞膜破裂。厚朴酚处理细胞的 SEM 分析导致细胞变形。TEM 显微照片显示细胞壁和质膜破裂，释放细胞内内容物，细胞壁肿胀。与 1μg/ml 两性霉素 B（Amp B）的 25.4%活性相比，厚朴酚在其最高 MIC 时的溶血活性为 11.9%。根据厚朴酚的 Lipinski 参数计算，表明其具有良好的口服生物利用度。对接研究表明，厚朴酚可能与真菌细胞膜中的麦角甾醇相互作用。综上所述，本研究为进一步研究厚朴酚提供了足够的证据，以便能够采用更好的策略来治疗口腔念珠菌病。
