Glucuronide metabolites of flavonolignans from milk thistle (Silybum marianum): Structural characterization

Milk thistle (Silybum marianum) is a commonly used herbal product, of which the crude extract, termed silymarin, is a well-known hepatoprotectant. Relative to conventional drugs, rigorous pharmacokinetic knowledge of herbal constituents is limited, largely due to the scarcity of reference standards. Glucuronidation is a conjugation reaction that plays a key detoxifying role in xenobiotic metabolism. Glucuronide metabolites are needed as reference standards to advance the understanding of silymarin metabolism, particularly with respect to situations when silymarin is taken in combination with drugs. The aim of this study was to identify the structures and the glucuronidation sites of chemoenzymatically synthesized glucuronides of one constituent, silybin A, by HRMS and NMR. Glucuronide biosynthesis resulted in three O-glucuronide regioisomers (1 – 3), with the highest yield from glucuronidation at the 7 position.