Department of Restorative Sciences, Faculty of Dentistry, Kuwait University, Kuwait City 13060, Kuwait.
Department of Bioclinical Sciences, Faculty of Dentistry, Kuwait University, Kuwait City 13060, Kuwait.
Int J Mol Sci. 2023 Jan 5;24(2):1046. doi: 10.3390/ijms24021046.
Oral candidiasis is an infection of the oral cavity commonly caused by Candida albicans. Endodontic treatment failure has also been found to be persistent from C. albicans in the root canal system. Despite the availability of antifungal drugs, the management of Candida oral infection is difficult as it exhibits resistance to a different class of antifungal drugs. Therefore, it is necessary to discover new antifungal compounds to cure fungal infections. This study aimed to examine the antifungal susceptibility of Capsaicin, an active compound of chili pepper. The susceptibility of Capsaicin and Fluconazole was tested against the Candida species by the CLSI (M27-A3) method. The effect of Capsaicin on the fungal cell wall was examined by the ergosterol inhibitory assay and observed by the scanning electron micrograph. The MIC range of Capsaicin against Candida isolates from oral (n = 30), endodontic (n = 8), and ATCC strains (n = 2) was 12.5−50 µg/mL. The MIC range of Fluconazole (128- 4 µg/mL) significantly decreased (2- to 4-fold) after the combination with Capsaicin (MIC/4) (p < 0.05). Capsaicin (at MIC) significantly reduced the mature biofilm of C. albicans by 70 to 89% (p < 0.01). The ergosterol content of the cell wall decreased significantly with the increase in the Capsaicin dose (p < 0.01). Capsaicin showed high sensitivity against the hyphae formation and demonstrated a more than 71% reduction in mature biofilm. A fluorescence microscopy revealed the membrane disruption of Capsaicin-treated C. albicans cells, whereas a micrograph of electron microscopy showed the distorted cells’ shape, ruptured cell walls, and shrinkage of cells after the release of intracellular content. The results conclude that Capsaicin had a potential antifungal activity that inhibits the ergosterol biosynthesis in the cell wall, and therefore, the cells’ structure and integrity were disrupted. More importantly, Capsaicin synergistically enhanced the Fluconazole antifungal activity, and the synergistic effect might be helpful in the prevention of Fluconazole resistance development and reduced drug-dosing.
口腔念珠菌病是一种常见的口腔感染，通常由白色念珠菌引起。根管系统中的白色念珠菌也被发现是根管治疗失败的持续原因。尽管有抗真菌药物可用，但由于其对不同类别的抗真菌药物表现出耐药性，因此口腔念珠菌感染的治疗仍然具有挑战性。因此，有必要发现新的抗真菌化合物来治疗真菌感染。本研究旨在研究辣椒素作为辣椒中的一种活性化合物的抗真菌敏感性。采用 CLSI（M27-A3）方法检测辣椒素和氟康唑对念珠菌属的抗真菌敏感性。通过麦角固醇抑制试验检测辣椒素对真菌细胞壁的影响，并通过扫描电子显微镜观察。从口腔（n=30）、牙髓（n=8）和 ATCC 菌株（n=2）分离的念珠菌对辣椒素的 MIC 范围为 12.5-50 µg/mL。与氟康唑（128-4 µg/mL）联合使用后，氟康唑的 MIC 范围（MIC/4）显著降低（2-4 倍）（p<0.05）。在 MIC 下，辣椒素显著降低成熟白念珠菌生物膜的形成 70-89%（p<0.01）。随着辣椒素剂量的增加，细胞壁中的麦角固醇含量显著降低（p<0.01）。辣椒素对菌丝形成表现出高度敏感性，并使成熟生物膜减少 71%以上。荧光显微镜显示，经辣椒素处理的白念珠菌细胞的膜破裂，而电子显微镜的显微照片显示，细胞内容物释放后，细胞形状变形，细胞壁破裂，细胞收缩。研究结果表明，辣椒素有抑制细胞壁麦角固醇生物合成的潜在抗真菌活性，因此细胞的结构和完整性受到破坏。更重要的是，辣椒素协同增强了氟康唑的抗真菌活性，协同作用可能有助于预防氟康唑耐药的发展和减少药物剂量。
