Polyphenols from Inula oculus-christi L. Induced Cell-Specific Membrane and Cytoskeleton Reorganization

Interrelations between the plasma membrane and cytoskeleton are of crucial importance for essential cellular processes such as endocytosis, formation of intercellular junctions, cell morphology, etc. Many studies validate the beneficial effects of polyphenols as antioxidant and protective agents, but a molecular mechanism of their interaction and transition through the plasma membranes of different cell lines is still missing. In this study, we examined the affinity of fractions enriched in flavonoid glycosides (FGs) and caffeoylquinic acids (CQAs), obtained from the methanol extract of the medicinal plant Inula oculus-christi L., to reorganize the plasma membrane structure and actin cytoskeleton by using confocal microscopy. Assessment of the degree of membrane ordering aiming to distinguish the ordered from disordered regions of the cellular membranes was performed using the fluorescent dye Di-4-ANEPPDHQ, and visualization of F-actin was by TRITC-phalloidin. Two epithelial cell lines with clear differences in their origin and plasma membrane organization were chosen: the non-malignant MDCK II and the cancerous A549. Our results showed that flavonoid glycosides exhibited an ordering effect on plasma membranes of cancerous cells and fluidized one on non-malignant cells. Different patterns of actin reorganization were observed for both cell lines after treatment. Our results indicate the potential of plant-derived polyphenols as modulators of the membrane's structural organization, offering valuable insights for the development of membrane-targeted therapeutic strategies.