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Am J Physiol Endocrinol Metab 293: E1503-E1510, 2007. First published September 11, 2007; doi:10.1152/ajpendo.00420.2007
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Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line

Dmitry Govorko,1 Sithes Logendra,1 Yanxin Wang,2 Debora Esposito,1 Slavko Komarnytsky,1 David Ribnicky,1 Alexander Poulev,1 Zhong Wang,3 William T. Cefalu,3 and Ilya Raskin1

1Biotech Center, 2Nutritional Sciences, Rutgers University, New Brunswick, New Jersey; and 3Pennington Biomedical Research Center, Baton Rouge, Louisiana

Submitted 3 July 2007 ; accepted in final form 24 August 2007

An ethanolic extract of Russian tarragon, Artemisia dracunculus L., with antihyperglycemic activity in animal models was reported to decrease phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in STZ-induced diabetic rats. A quantitative polymerase chain reaction (qPCR) assay was developed for the bioactivity-guided purification of the compounds within the extract that decrease PEPCK expression. The assay was based on the inhibition of dexamethasone-stimulated PEPCK upregulation in an H4IIE hepatoma cell line. Two polyphenolic compounds that inhibited PEPCK mRNA levels were isolated and identified as 6-demethoxycapillarisin and 2',4'-dihydroxy-4-methoxydihydrochalcone with IC50 values of 43 and 61 µM, respectively. The phosphoinositide-3 kinase (PI3K) inhibitor LY-294002 showed that 6-demethoxycapillarisin exerts its effect through the activation of the PI3K pathway, similarly to insulin. The effect of 2',4'-dihydroxy-4-methoxydihydrochalcone is not regulated by PI3K and dependent on activation of AMPK pathway. These results indicate that the isolated compounds may be responsible for much of the glucose-lowering activity of the Artemisia dracunculus extract.

phosphoenolpyruvate carboxykinase; polyphenols; diabetes


Address for reprint requests and other correspondence: D. Govorko, Rutgers University, Biotech Center, 59 Dudley Road, New Brunswick, NJ 08901 (e-mail: govorko{at}aesop.rutgers.edu)




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