Differential transcriptional profiles in HepG2 cells after the exposure to a chemically characterized complex preparation of Silybi mariani fructus and its chemically defined constituent silybin A + B

SummaryBackgroundMilk thistle is a herbal substance traditionally used. Several studies suggest that silymarin acts liver protective. Our objective was to compare hepatocellular effects of a chemically characterized preparation of Silybi mariani fructus to its designated bioactive constituent silybin A + B by gene expression profiling.MethodsSilybi mariani fructus was extracted (70%, V/V ethanol) and chemically characterized by means of 1H NMR analysis and silymarin was quantified (HPLC). Cell proliferation was investigated after exposure to the extract and silybin A + B. Gene expression profiles (Whole Genome Gene Expression Microarrays v2, Agilent Technologies) were analyzed. Selected genes were validated by qRT-PCR.Results1H-NMR analyses suggested that various groups of constituents were present in the complex extract. HepG2 cells were exposed to the extract silymarin (9.6 μg/ml) and silybin A + B (9.6 μg/ml). Gene expression profiling revealed differential cellular responses. Silybin A + B altered signal cascades related to cell death and proliferation, while cellular functions affected by the extract were associated with drug metabolism, cell morphology and cell assembly and organization. Common to both treatments were signal cascades, such as involvement of liver-toxic pathways, but also liver regeneration.ConclusionAlthough cell proliferation was not affected by silybin A + B or the extract, gene expression profiles revealed differently activated cellular mechanisms. This emphasizes that the biological function of multicomponent mixtures may differ widely from the one of the designated bioactive constituent. A comparative gene expression is likely to expidize bioguided fractionations with the identification of relevant signal cascades and networks which allow to generate hypotheses for antagonistic, additive or synergistic cellular processes.