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Effects of Silymarin on the Metabolome


EMSL Project ID
48229

Abstract

Silymarin (SM)-derived natural products interact with mammalian biomolecules in a specific and productive manner to cause changes in signal transduction and gene expression in a cell to protect the liver. To address the hypothesis, we are using two parallel approaches to discover the mechanisms of action of SM. First, we are using microarray analysis to identify the transcriptional changes of liver cell lines and primary hepatocyte cultures treated with SM and SM-derived pure compounds. Second, using photoaffinity click chemistry, we are capturing and validating cellular targets of SM compounds using mass spectrometry. Microarray data indicate that SM induces rapid changes in hepatocellular gene expression within 4-8 hours after exposure. Intriguingly, many of the changes are in genes associated with cell proliferation and metabolism. These and other emerging data suggest that SM is inducing a rapid metabolic reprogramming of cells. Thus, the purpose of this administrative supplement is to define how SM modulates the metabolome. The inclusion of metabolomics will allow us to illuminate, to an unprecedented level of detail, exactly how health-promoting natural products such as SM exert their beneficial effects. The novel data emanating from this expanded research project may establish new paradigms for how cells respond to natural products, which may ultimately lead to refinements in natural product treatments and/or drug development opportunities for a multitude of human diseases.

Project Details

Start Date
2014-01-01
End Date
2016-09-30
Status
Closed

Team

Principal Investigator

Thomas Metz
Institution
Pacific Northwest National Laboratory

Team Members

Jennifer Kyle
Institution
Pacific Northwest National Laboratory

Related Publications

Lovelace ES, J Wagoner, J MacDonald, T Bammler, J Bruckner, J Brownell, R Beyer, EM Zink, YM Kim, JE Kyle, BJM Webb-Robertson, KM Waters, TO Metz, F Farin, and S Polyak. 2015. "Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling." Journal of Natural Products epub ahead of print:, doi:10.1021/acs.jnatprod.5b00288