Aim:Silybin(silibinin)is major biologically active flavonolignan extracted frommilk thistle(Sylibum marianum).Its biological activities include hepato-protection,anticancer properties,and antioxidant-and membrane-stabilizing functions.Al-though membranes are postulated to be one of the cellular targets for silybin,littleis known about its interaction with phospholipid bilayers.Methods:In the presentwork,the interactions of silybin with phosphatidylcholine bilayers were studiedin detail using fluorescence spectroscopy,microcalorimetry and electron spinresonance techniques.Results:The results showed that silybin interacted withthe surface of lipid bilayers.It affected the generalized polarization of the fluores-cent probe Prodan,while not influencing the more deeply located Laurdan.Silybinlowered the main phospholipid phase transition temperature as judged bymicrocalorimetry,and caused the immobilization of spin probe Tempo-palmitatelocated on the surface of membranes.The mobility of spin probes 5-and 16-doxylstearic acid was not affected by silybin.Silybin-induced quenching of 1,6-diphe-nyl-1,3,5-hexatriene fluorescence indicated that some flavonoid molecules parti-tioned into the hydrophobic region of membranes,which did not change signifi-cantly the biophysical properties of the deeper membrane regions.Conclusion:Such a behavior of silybin in membranes is in accordance with its postulatedbiological functions and neglectable side effects of therapies using silybin. Aim:Silybin(silibinin)is major biologically active flavonolignan extracted frommilk thistle(Sylibum marianum).Its biological activities include hepato-protection,anticancer properties,and antioxidant-and membrane-stabilizing functions.Al-though membranes are postulated to be one of the Cellular targets for silybin,littleis known about its interaction with phospholipid bilayers.Methods:In the present work,the interactions of silybin with phosphatidylcholine bilayers were studiedin detail using fluorescence spectroscopy,microcalorimetry and electron spinresonance techniques.Results:The results showed that silybin interacted with the surface Of lipid bilayers.It affected the generalized polarization of the fluores-cent probe Prodan,while not influencing the more deeply located Laurdan.Silybinlowered the main phospholipid phase transition temperature as judged by microcalorimetry, and caused the immobilization of spin probe Tempo-palmitatelocated on the surface Of membranes.The mobility of spi n probes 5-and 16-doxylstearic acid was not affected by silybin.Silybin-induced quenching of 1,6-diphe-nyl-1,3,5-hexatriene fluorescence indicated that some flavonoid molecules parti-tioned into the hydrophobic region of membranes ,which did not change signifi-cantly the biophysical properties of the deeper membrane regions.Conclusion:Such a behavior of silybin in membranes is in accordance with its postulatedbiological functions and neglectable side effects of therapies using silybin.