title: Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line.
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.
authors.affiliation: Rutgers University, Biotech Center, 59 Dudley Road, New Brunswick, NJ 08901, USA. govorko@aesop.rutgers.edu
authors.forename: Dmitry
authors.initials: D
authors.lastname: Govorko
authors.forename: Sithes
authors.initials: S
authors.lastname: Logendra
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Wang
authors.forename: Debora
authors.initials: D
authors.lastname: Esposito
authors.forename: Slavko
authors.initials: S
authors.lastname: Komarnytsky
authors.forename: David
authors.initials: D
authors.lastname: Ribnicky
authors.forename: Alexander
authors.initials: A
authors.lastname: Poulev
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: Ilya
authors.initials: I
authors.lastname: Raskin
mesh_terms: D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D045744:Cell Line, Tumor; D047188:Chalcones / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D002867:Chromones / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D010636:Phenols / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D018520:Plant Shoots / Q000737:chemistry; D059808:Polyphenols; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: C514624:2',4'-dihydroxy-4-methoxydihydrochalcone; C514569:6-demethoxycapillarisin; D047188:Chalcones; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007004:Hypoglycemic Agents; D007328:Insulin; D009025:Morpholines; D010636:Phenols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D059808:Polyphenols; D011720:Pyrazoles; D011743:Pyrimidines; D012333:RNA, Messenger; D013873:Thionucleotides; C516138:dorsomorphin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C015929:8-((4-chlorophenyl)thio)cyclic-3',5'-AMP; D003907:Dexamethasone; D000242:Cyclic AMP; C494923:Akt2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose