Research

Studies on the Milk Thistle

My research team has been studying the chemistry of milk thistle (Silybum marianum) for over a decade. For the most part, this has involved the isolation and characterization of reference standards from the crude extract, which is termed ‘silymarin’. Not only are we able to isolate and characterize all seven major diastereoisomers in silymarin, but we are able to do so on the gram scale, providing ample materials for in vivo studies. We initiated much of this research via funding from the National Toxicology Program, and that evolved into a research collaboration funded by the National Cancer Institute to examine the prostate cancer chemopreventive properties of milk thistle, in fruitful collaboration with Dr. Rajesh Agarwal at the University of Colorado and Dr. David Kroll. Currently, we are also exploring the Mechanisms of Silymarin Hepatoprotection via funding from the National Center for Complementary and Alternative Medicine in a project led by Dr. Steve Polyak at the University of Washington. Also, we are examining the metabolism of the constituents in milk thistle, particularly in relation to drug-diet interactions in the gut, via funding from the National Institute of General Medical Sciences in a project led by Dr. Mary Paine at the University of North Carolina at Chapel Hill.

Selected Publications:

“Differential in Vitro Effects of Intravenous Versus Oral Formulations of Silibinin on the HCV Life Cycle and Inflammation.”
Jessica Wagoner, Chihiro Morishima, Tyler N. Graf, Nicholas H. Oberlies, Elodie Teissier, Eve-Isabelle Pécheur, John E. Tavis, and Stephen J. Polyak
PLoS One, 2011, 6, e16464.
PMID:21297992; PMC3030583; doi: 10.1371/journal.pone.0016464

“Identification of Hepatoprotective Flavonolignans from Silymarin.”
Stephen J. Polyak, Chihiro Morishima, Volker Lohmann, Sampa Pal, David Y. W. Lee, Yanze Liue, Tyler N. Graf, and Nicholas H. Oberlies
Proceedings of the National Academy of Sciences USA, 2010, 107, 5995-5999.
PMID: 20231449; PMCID: PMC2851903; doi: 10.1073/pnas.0914009107

“Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations.”
Scott J. Brantley, Nicholas H. Oberlies, David J. Kroll, and Mary F. Paine
Journal of Pharmacology and Experimental Therapeutics, 2010, 332, 1081-1087.
PMID:19934397; PMCID: PMC2835426; doi: 10.1124/jpet.109.161927

“Isosilybin A Induces Apoptosis in Human Prostate Cancer Cells Via Targeting Akt, NF-kappaB, and Androgen Receptor Signaling.”
Gagan Deep, Subhash C. Gangar, Nicholas H. Oberlies, David J. Kroll, and Rajesh Agarwal
Molecular Carcinogenesis, 2010, 49, 902-912.
PMID:20721970; doi: 10.1002/mc.20670

“Silymarin Inhibits in Vitro T Cell Proliferation and Cytokine Production in Hepatitis C Virus Infection.”
Chihiro Morishima, Margaret C. Shuhart, Chia C. Wang, Denise M. Paschal, Minjun C. Apodaca, Yanze Liu, Derek D. Sloan, Tyler N. Graf, Nicholas H. Oberlies, David Y.–W. Lee, Keith R. Jerome, and Stephen J. Polyak
Gastroenterology, 2010, 138, 671-681.
PMID:19782083; PMCID: PMC2819600; doi: 10.1053/j.gastro.2009.09.021

“Gram-Scale Purification of Flavonolignan Diastereoisomers from Silybum marianum (Milk Thistle) Extract in Support of Preclinical in Vivo Studies for Prostate Cancer Chemoprevention.”
Tyler N. Graf, Mansukh C. Wani, Rajesh Agarwal, David J. Kroll, and Nicholas H. Oberlies
Planta Medica, 2007, 73, 1495-1501.
PMID: 17948171; doi: 10.1055/s-2007-990239

“Milk Thistle Nomenclature: Why It Matters in Cancer Research and Pharmacokinetic Studies.”
David J. Kroll, Heather S. Shaw, and Nicholas H. Oberlies
Integrative Cancer Therapies, 2007, 6, 110-119.
PMID: 17548790; doi: 10.1177/1534735407301825