Identification of Isosilybin a from Milk Thistle Seeds as an Agonist of Peroxisome Proliferator-Activated Receptor Gamma

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Nicholas Oberlies, Patricia A. Sullivan Distinguished Professor of Chemistry (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: Peroxisome proliferator-activated receptor gamma (PPAR?) is a key regulator of glucose and lipid metabolism. Agonists of this nuclear receptor are used in the treatment of type 2 diabetes and are also studied as a potential treatment of other metabolic diseases, including nonalcoholic fatty liver disease. Silymarin, a concentrated phenolic mixture from milk thistle (Silybum marianum) seeds, is used widely as a supportive agent in the treatment of a variety of liver diseases. In this study, the PPAR? activation potential of silymarin and its main constituents was investigated. Isosilybin A (3) caused transactivation of a PPAR?-dependent luciferase reporter in a concentration-dependent manner. This effect could be reversed upon co-treatment with the PPAR? antagonist T0070907. In silico docking studies suggested a binding mode for 3 distinct from that of the inactive silymarin constituents, with one additional hydrogen bond to Ser342 in the entrance region of the ligand-binding domain of the receptor. Hence, isosilybin A (3) has been identified as the first flavonolignan PPAR? agonist, suggesting its further investigation as a modulator of this nuclear receptor.

Additional Information

Journal of Natural Products, 77(4), 842-847.
Language: English
Date: 2014
Isosilybin A, silymarin, milk thistle, peroxisome proliferator-activated receptors

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