Wyżga Beata, Skóra Magdalena, Olechowska Karolina, Hąc-Wydro Katarzyna
Jagiellonian University, Faculty of Chemistry, Gronostajowa 2, 30-387 Kraków, Poland; Jagiellonian University, Doctoral School of Exact and Natural Sciences, Łojasiewicza 11, 30-348 Kraków, Poland.
Jagiellonian University Medical College, Chair of Microbiology, Department of Infections Control and Mycology, Czysta 18, 31-121 Kraków, Poland.
Biochim Biophys Acta Biomembr. 2025 Jun;1867(5-6):184423. doi: 10.1016/j.bbamem.2025.184423. Epub 2025 May 5.
Hinokitiol (β-thujaplicin) is a naturally occurring substance of antimicrobial properties, which can be used e.g. as a cosmetic preservative. In this work the influence of hinokitiol on the monolayers and bilayers formed from fungal membrane lipids (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine - POPE; 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine - POPC and ergosterol) was investigated. These studies aimed to investigate the effect of hinokitiol on fungal membranes, being indicated as a target for this compound. In this context, the affinity of hinokitiol for ergosterol-containing membranes was of particular interest. The in vitro antifungal activity of hinokitiol was also determined. The results showed that hinokitiol is active against the Candida species tested and exhibits stronger antifungal than antibacterial activity. Moreover, hinokitiol alters the properties of model membranes and the observed effects correlated with ergosterol content in the system. Namely, the higher the ergosterol content, the greater the fluidizing and destabilising effect of hinokitiol and its removal from the model. Moreover, hinokitiol is not able to penetrate into ergosterol membranes; instead, causes strong destabilization of the film and dragging the monolayer material into the subphase. Thus, hinokitiol changes properties of model membrane by the exclusion of the molecules from the interface. The results evidenced differences in the interactions of hinokitiol with ergosterol vs phospholipids, and the interactions of hinokitiol with the membrane depend on the presence and levels of ergosterol. Thus, ergosterol can be a molecular target for this compound. Moreover, the presence of ergosterol in fungal membranes and its lack in bacteria membranes may explain stronger antifungal vs antibacterial effect of hinokitiol.
扁柏酚（β-崖柏素）是一种具有抗菌特性的天然物质，可用于例如作为化妆品防腐剂。在这项工作中，研究了扁柏酚对由真菌膜脂质（1-棕榈酰-2-油酰基-sn-甘油-3-磷酸乙醇胺 - POPE；1-棕榈酰-2-油酰基-sn-甘油-3-磷酸胆碱 - POPC和麦角固醇）形成的单层膜和双层膜的影响。这些研究旨在研究扁柏酚对真菌膜的作用，表明真菌膜是该化合物的作用靶点。在此背景下，扁柏酚对含麦角固醇膜的亲和力尤其令人感兴趣。还测定了扁柏酚的体外抗真菌活性。结果表明，扁柏酚对所测试的念珠菌属具有活性，并且表现出比抗菌活性更强的抗真菌活性。此外，扁柏酚改变了模型膜的性质，观察到的效果与系统中的麦角固醇含量相关。即，麦角固醇含量越高，扁柏酚的流化和去稳定作用以及其从模型中去除的效果就越大。此外，扁柏酚无法穿透麦角固醇膜；相反，会导致膜的强烈去稳定并将单层材料拖入亚相。因此，扁柏酚通过将分子从界面排除来改变模型膜性质。结果证明了扁柏酚与麦角固醇和磷脂相互作用的差异，并且扁柏酚与膜的相互作用取决于麦角固醇的存在和水平。因此，麦角固醇可能是该化合物分子靶点。此外，真菌膜中存在麦角固醇而细菌膜中缺乏麦角固醇可能解释了扁柏酚更强的抗真菌与抗菌作用。
