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Biomembrane interactions of flavonoids and alkyl gallates were investigated using transport studies on Caco-2 cells and membrane affinity experiments in phospholipid vesicles. Flavone was rapidly absorbed across the cell monolayer (Papp,380×10−6 cm/s), whereas efficient uptake but no apical to basolateral transport was observed with the flavonoids with higher degree of hydroxylation (e.g., quercetin and luteolin). The transport of alkyl gallates was governed by the length of the alkyl chain, i.e., methyl and propyl gallate were absorbed while octyl gallate showed cellular uptake but no transport. Flavonoids with several hydroxyl groups exhibited highest affinity for vesicle membranes, partition coefficients being 7.1 and 7.5 μM for luteolin and quercetin, respectively. In conclusion, the degree of hydroxylation, molecular configuration, and length of the side chain of flavonoids and alkyl gallates seem to have a highly important impact on their membrane affinity as well as on their permeability characteristics in Caco-2 cells. [Copyright &y& Elsevier]

The flavonoids comprise a large group of polyphenolic compounds that are ubiquitous in vegetables, berries, and fruits, and they have been shown to possess antioxidative activity. The interactions between flavonoids and membranes composed of dipalmitoylphosphatidylcholine (DPPC) have been studied by means of noncovalent immobilized artificial membrane (IAM) chromatography. We have also investigated flavonoid-induced calcein release from fluid egg phosphatidylcholine (EPC) vesicles. Flavonoids with more hydroxyl groups showed longer retention delays in the IAM studies, suggesting stronger interactions between the flavonoids, which are rich in hydroxyl groups, and the DPPC membrane interface. We also observed an inverse correlation between the number of hydroxyl groups in the flavonoids and their capacity to induce calcein leakage through fluid EPC bilayer membranes (the more nonpolar flavonoids caused more calcein leakage). Rhamnetin and morin, however, both showed marked activity for the DPPC membrane interface and caused significant membrane leakage. Both polar and nonpolar forces were shown to have a significant impact on the flavonoid/biomembrane interactions. [Copyright &y& Elsevier]

Actinoporins are a family of pore-forming toxins produced by sea anemones as part of their venomous cocktail. These proteins remain soluble and stably folded in aqueous solution, but when interacting with sphingomyelin-containing lipid membranes, they become integral oligomeric membrane structures that form a pore permeable to cations, which leads to cell death by osmotic shock. Actinoporins appear as multigenic families within the genome of sea anemones: several genes encoding very similar actinoporins are detected within the same species. The Caribbean Sea anemone Stichodactyla helianthus produces three actinoporins (sticholysins I, II and III; StnI, StnII and StnIII) that differ in their toxic potency. For example, StnII is about four-fold more effective than StnI against sheep erythrocytes in causing hemolysis, and both show synergy. However, StnIII, recently discovered in the S. helianthus transcriptome, has not been characterized so far. Here we describe StnIII's spectroscopic and functional properties and show its potential to interact with the other Stns. StnIII seems to maintain the well-preserved fold of all actinoporins, characterized by a high content of β-sheet, but it is significantly less thermostable. Its functional characterization shows that the critical concentration needed to form active pores is higher than for either StnI or StnII, suggesting differences in behavior when oligomerizing on membrane surfaces. Our results show that StnIII is an interesting and unexpected piece in the puzzle of how this Caribbean Sea anemone species modulates its venomous activity. • StnIII shows spectroscopic features compatible with the actinoporin fold. • It is active against red blood cells, but much less hemolytic than StnII. • StnIII is significantly less stable than StnI or StnII. • Functionality results suggest StnIII making a pore of different stoichiometry. [ABSTRACT FROM AUTHOR]