Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line
| Autor: | Sithes Logendra, Debora Esposito, William T. Cefalu, Yanxin Wang, Dmitry Govorko, David M. Ribnicky, Alexander Poulev, Slavko Komarnytsky, Ilya Raskin, Zhong Q. Wang |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Physiology Endocrinology Diabetes and Metabolism Morpholines Gene Expression Carbohydrate metabolism Dexamethasone Chalcones Phenols Physiology (medical) Internal medicine Cell Line Tumor Gene expression medicine Cyclic AMP Animals Hypoglycemic Agents Insulin RNA Messenger Enzyme Inhibitors Phosphorylation Phosphoinositide-3 Kinase Inhibitors Flavonoids biology Plant Extracts Gluconeogenesis Polyphenols Thionucleotides biology.organism_classification Dracunculus (nematode) Rats Endocrinology Glucose Pyrimidines Biochemistry Artemisia Cell culture Polyphenol Chromones Pyrazoles Phosphoenolpyruvate Carboxykinase (GTP) Phosphoenolpyruvate carboxykinase Proto-Oncogene Proteins c-akt Plant Shoots |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 293(6) |
| ISSN: | 0193-1849 |
| Popis: | An ethanolic extract of Russian tarragon, Artemisia dracunculus L., with antihyperglycemic activity in animal models was reported to decrease phospho enolpyruvate 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 IC50values 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. |
| Databáze: | OpenAIRE |
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