Silymarin is a special fruit extract from milk thistle (Silybum marianum (L.) Gaertn., Asteraceae) predominantly consisting of stereo- and regioisomeric flavonolignans. It is mainly used for the supportive treatment of liver diseases. Since the oral bioavailability of S. marianum flavonolignans is very low [1], they presumably reach the colon and may be metabolized by gut microbes.
In order to assess gut microbial metabolization of the main constituents of Silymarin, it was incubated (0.21 mg/ml) with 0.1% human fecal suspension under physiological conditions (anoxic, 37°C). Samples were taken after 0.5 h, 4 h and 24 h of incubation and analyzed by LC-MS metabolomics for metabolic profile changes.
After 4 h of incubation, dihydroquercetin, the main Silymarin flavonoid, was almost completely metabolized, while the flavonolignan levels did not yet significantly change. 3-(3-Hydroxyphenyl)- and 3-(4-hydroxyphenyl)propionic acid were identified as putative dihydroquercetin metabolites.
After 24 h of incubation, also the levels of all main Silybum flavonolignans were significantly reduced, and three different series of main putative flavonolignan metabolites could be detected on the basis of HRMS data: (a) Four compounds with a molecular weight of 484.1364 were tentatively assigned as metabolites formed by cleavage of the dioxane ring; (b) two compounds with molecular weight 468.1050 were tentatively assigned as demethylation products; (c) five compounds with molecular weight 470.1207 were tentatively assigned as metabolites formed by demethylation plus dioxan ring cleavage.
These results indicate that human gut bacteria may indeed be capable to metabolize S. marianum flavonolignans. Semipreparative isolation and NMR-based structure elucidation of the flavonolignan metabolites are in progress.
Figure: Main constituents of Silymarin
Reference:
Calani, L. et al. Phytomedicine (2012) 20,. 40-46.