Silymarin is a well-known standardized extract from the seeds of milk thistle (Silybum marianum L., Asteraceae) with a pleiotropic effect on human health, including skin anticancer potential. Detailed characterization of flavonolignans properties affecting interactions with human skin was of interest. The partition coefficients log Pow of main constitutive flavonolignans, taxifolin and their respective dehydro derivatives were determined by a High Performance Liquid Chromatography (HPLC) method and by mathematical (in silico) approaches in n-octanol/water and model lipid membranes. These parameters were compared with human skin intake ex vivo. The experimental log Pow values for individual diastereomers were estimated for the first time. The replacement of n-octanol with model lipid membranes in the theoretical lipophilicity estimation improved the prediction strength. During transdermal transport, all the studied compounds permeated the human skin ex vivo; none of them reached the acceptor liquid. Both experimental/theoretical tools allowed the studied polyphenols to be divided into two groups: low (taxifolin, silychristin, silydianin) vs. high (silybin, dehydrosilybin, isosilybin) lipophilicity and skin intake. In silico predictions can be usefully applied for estimating general lipophilicity trends, such as skin penetration or accumulation predictions. However, the theoretical models cannot yet provide the dermal delivery differences of compounds with very similar physico-chemical properties; e.g., between diastereomers.

Department of Medical Chemistry and Biochemistry Faculty of Medicine and Dentistry Palacký University Hněvotínská 3 775 15 Olomouc Czech Republic

Department of Plastic and Aesthetic Surgery University Hospital Olomouc 1 P Pavlova 6 779 00 Olomouc Czech Republic

Institute of Microbiology Laboratory of Biotransformation Academy of Sciences of the Czech Republic Vídeňská 1083 142 20 Prague Czech Republic

KTH Royal Institute of Technology School of Engineering Sciences in Chemistry Biotechnology and Health Department of Theoretical Chemistry and Biology S 106 91 Stockholm Sweden

Regional Centre of Advanced Technologies and Materials Department of Physical Chemistry Faculty of Science Palacký University tř 17 listopadu 12 771 46 Olomouc Czech Republic

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