Lipid membrane composition modulates Hinokitiol's effects on keratinocytes and fibroblasts

Hinokitiol (β-thujaplicin) is a natural antimicrobial agent used in cosmetics. The aim of presented studies was to gain insight into the interactions of hinokitiol with lipids in model membranes and to correlate this with the selective effect of hinokitiol on cells. To reach this goal, the toxicity of hinokitiol was evaluated using keratinocyte and fibroblast cell lines, and studies were performed on lipid monolayers (both one component and mixed systems). During investigations the surface pressure - area measurements, penetration studies and Brewster angle microscopy experiments were done. The analysis of the parameters calculated from the experimental data and the comparison of BAM images evidenced that, at membrane – related surface pressure, hinokitiol does not insert into model keratinocyte and fibroblast membranes and its impact on these systems is very weak. This important conclusion correlates with the in vitro experiments. The results for one component systems evidenced that the effect of hinokitiol on mammalian lipid films depends on the monolayer organisation and the lipid structure (especially the lipid polar head). In consequence, the type and proportion of lipids determines the effect of hinokitiol on the mixed films. The latter corroborates with the differences in the influence of hinokitiol on bacteria compared to mammalian lipids. It was concluded that hinokitiol exhibits selective activity toward bacterial cells compared to mammalian cells and their corresponding model membranes. Thus, the predominance of hinokitiol's antibacterial properties over its toxicity to skin cells may therefore be related to interactions of this compound with membrane lipids.