Department of Biochemistry, Maharshi Dayanand University, Rohtak, Haryana, India.
Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India.
Int Microbiol. 2024 Apr;27(2):423-434. doi: 10.1007/s10123-023-00401-w. Epub 2023 Jul 22.
Candida spp. is a significant cause of topical and fungal infections in humans. In addition to Candida albicans, many non-albicans species such as C. krusei, C. glabrata, C. parapsilosis, C. tropicalis, C. guilliermondii cause severe infections. The main antifungal agents belong to three different classes, including azoles, polyenes, and echinocandins. However, resistance to all three categories of drugs has been reported. Therefore, there is an urgent need to search for other alternatives with antifungal activity. Many herbal extracts and compounds from natural sources show excellent antifungal activity. In this study, we used an oil extract from the fruits of Zanthoxylum armatum, which showed significant antifungal activity against various Candida spp. by two different methods-minimum inhibitory concentration (MIC) and agar diffusion. In addition, we attempted to explore the possible mechanism of action in C. albicans. It was found that the antifungal activity of Z. armatum oil is fungicidal and involves a decrease in the level of ergosterol in the cell membrane. The decrease in ergosterol level resulted in increased passive diffusion of a fluorescent molecule, rhodamine6G, across the plasma membrane, indicating increased membrane fluidity. The oil-treated cells showed decreased germ tube formation, an important indicator of C. albicans' virulence. The fungal cells also exhibited decreased attachment to the buccal epithelium, the first step toward invasion, biofilm formation, and damage to oral epithelial cells. Interestingly, unlike most antifungal agents, in which the generation of reactive oxygen species is responsible for killing, no significant effect was observed in the present study.
假丝酵母属是引起人类局部和真菌感染的重要原因。除了白假丝酵母外，许多非白假丝酵母如克柔假丝酵母、光滑假丝酵母、近平滑假丝酵母、热带假丝酵母、季也蒙假丝酵母等也会引起严重感染。主要的抗真菌药物属于三类，包括唑类、多烯类和棘白菌素类。然而，已经报道了对所有三类药物的耐药性。因此，迫切需要寻找具有抗真菌活性的其他替代品。许多来自天然来源的草药提取物和化合物显示出优异的抗真菌活性。在这项研究中，我们使用了来自花椒果实的油提取物，该提取物通过两种不同的方法——最小抑菌浓度（MIC）和琼脂扩散法，显示出对各种假丝酵母属的显著抗真菌活性。此外，我们试图探索其在白假丝酵母中的可能作用机制。研究发现，花椒油的抗真菌活性是杀菌性的，涉及细胞膜中麦角固醇水平的降低。麦角固醇水平的降低导致荧光分子罗丹明 6G 穿过质膜的被动扩散增加，表明膜流动性增加。经油处理的细胞显示出减少的芽管形成，这是白假丝酵母毒力的一个重要指标。真菌细胞还表现出对口腔上皮细胞的附着减少、生物膜形成和损伤，而这些都是入侵的第一步。有趣的是，与大多数抗真菌药物不同，在这些药物中，活性氧的产生是导致细胞死亡的原因，但在本研究中没有观察到明显的效果。
