Abstract
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 IC(50) values of 43 and 61 muM, 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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Artemisia / chemistry*
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Cell Line, Tumor
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Chalcones / analysis
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Chalcones / isolation & purification
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Chalcones / pharmacology*
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Chromones / analysis
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Chromones / isolation & purification
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Chromones / pharmacology*
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Cyclic AMP / analogs & derivatives
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Cyclic AMP / pharmacology
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Dexamethasone / pharmacology
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Enzyme Inhibitors / pharmacology
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Flavonoids / analysis
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Flavonoids / isolation & purification
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Flavonoids / pharmacology
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Gene Expression / drug effects*
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Gluconeogenesis / drug effects*
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Glucose / metabolism
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Hypoglycemic Agents / analysis
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Hypoglycemic Agents / isolation & purification
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Hypoglycemic Agents / pharmacology
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Insulin / pharmacology
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Morpholines / pharmacology
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Phenols / analysis
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Phenols / isolation & purification
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Phenols / pharmacology
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Phosphoenolpyruvate Carboxykinase (GTP) / genetics*
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation / drug effects
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Plant Extracts / pharmacology
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Plant Shoots / chemistry
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Polyphenols
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Proto-Oncogene Proteins c-akt / metabolism
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Pyrazoles / pharmacology
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Pyrimidines / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rats
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Thionucleotides / pharmacology
Substances
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2',4'-dihydroxy-4-methoxydihydrochalcone
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6-demethoxycapillarisin
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Chalcones
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Chromones
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Enzyme Inhibitors
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Flavonoids
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Hypoglycemic Agents
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Insulin
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Morpholines
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Phenols
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Phosphoinositide-3 Kinase Inhibitors
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Plant Extracts
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Polyphenols
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Pyrazoles
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Pyrimidines
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RNA, Messenger
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Thionucleotides
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dorsomorphin
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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8-((4-chlorophenyl)thio)cyclic-3',5'-AMP
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Dexamethasone
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Cyclic AMP
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Akt2 protein, rat
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Proto-Oncogene Proteins c-akt
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Phosphoenolpyruvate Carboxykinase (GTP)
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Glucose