Submitted on July 3, 2007
Accepted on August 24, 2007
Polyphenolic Compounds from Artemisia dracunculus L. Inhibit PEPCK Gene Expression and Gluconeogenesis in an H4IIE Hepatoma Cell Line
Dmitry Govorko1*, Sithes Logendra1, Yanxin Wang2, Debora Esposito1, Slavko Komarnytsky1, David M Ribnicky1, Alexander Poulev1, Zhong Q Wang3, William T. Cefalu4, and Ilya Raskin1
1 Biotech Center, Rutgers University, New Brunswick, New Jersey, United States
2 Nutritional Sciences, Rutgers University, New Brunswick, New Jersey, United States
3 Diabetes, PBRC, Baton Rouge, Louisiana, United States
4 Division of Nutrition and Chronic Diseases, Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States
* To whom correspondence should be addressed. E-mail: govorko{at}aesop.rutgers.edu.
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 43µM and 61 µM, respectively. The phosphoinositide-3 kinase (PI3K) inhibitor, LY294002, 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.
