Phloretin modulates the rate of channel formation by polyenes

• Membrane activity of flavonoids and polyene antibiotics has been studied via calcein release, calorimetry, planar bilayers.
• Phloretin and biochanin A fluidize lipid membrane while catechin and daidzein do not.
• Phloretin enhances membrane activity of polyene antibiotics via action on the lipid mouth of the asymmetric polyene channel.
• Biochanin A inhibits polyene activity.

The influence of flavonoids and polyene antibiotics on the permeability of membranes has been investigated through measurements of calcein leakage from large unilamellar vesicles composed of DOPC:cholesterol (67:33 mol%). Phloretin and biochanin A have been shown to induce calcein release from liposomes, but quercetin, daidzein, and catechin have not. Differential scanning calorimetry has indicated a decreasing of melting temperature of DPPC vesicles by 1.5–2 °C in the presence of phloretin and biochanin A. Quercetin, catechin, and daidzein have had almost no effect on the main transition temperature. Phloretin, biochanin A, and quercetin have significantly broadened the main transition peak of DPPC. Phloretin have increased a leakage induced by polyene antibiotics, whereas catechin and daidzein have not. Quercetin has slightly affected it. The effects of tested flavonoids on the polyene-induced calcein leakage and channel forming activity have been similar. The obtained data agree with the previously supposed hypothesis regarding the enhancement of polyene activity by reducing elastic stress near the lipid mouth of the nystatin pore. The inhibition of polyene channel forming activity by biochanin A observed in planar DOPC:cholesterol bilayers may be related to the flavonoid competition with cholesterol in the polyene–sterol channel complexes.

Figure optionsDownload high-quality image (216 K)Download as PowerPoint slide