In vitro and ex vivo Cutaneous Bioavailability and Biotransformation of Silymarin and Its Constituents

Silymarin (SM), an extract from the fruits of the milk thistle (Silybum marianum L., Asteraceae), has pleiotropic effects on human health. SM's biological activity assigns to its constitutive polyphenols, mainly flavonolignans. SM has become increasingly interesting for dermal applications. There are currently several commercial dermatological preparations available on the market containing SM or its dominant flavonolignan silybin (SB) as the active ingredients. The metabolic transformation of compounds in skin including SM's polyphenols has only been marginally investigated. Therefore, this study focused on the metabolization of SM and its pure polyphenols (SB, isosilybin [ISB], 2,3-dehydrosilybin [DHSB], silychristin [SC], silydianin [SD], and taxifolin [TA]) in the skin.

Human skin ex vivo (HSE) and normal human dermal fibroblasts (NHDF) were used as experimental models. For cell treatment, a concentration of 10 μmol L-1 (pure compounds) or 4.825 mg L-1 (SM) was used. For HSE treatment, 50 μmol L-1 (pure compounds) or 24.124 mg L-1 (SM) was used.

The penetration of studied polyphenols into the skin correlated with their lipophilicity (DHSB>ISB>SB>SC>SD>TA). The bioavailability of SM's polyphenols was relatively high, and thus the substances can be expected to modulate biological processes in the region close to their application site. SM's polyphenol metabolites of the first and second phase of biotransformation were identified in NHDF and HSE.

In HSE, the metabolic transformation of SM's components and its pure polyphenols was more extensive, as skin fragments are a more complex cellular and metabolically active system. Human skin ex vivo seems to be a useful tool for studying compounds biotransformation at topical application.