title: Palmatine activates AhR and upregulates CYP1A activity in HepG2 cells but not in human hepatocytes.
abstract: The protoberberine alkaloid palmatine is present in preparations from medicinal plants such as Coptis chinensis and Corydalis yanhusuo. This study examined whether palmatine affects the expression of cytochromes P450 (CYPs) 1A1 and 1A2 in primary cultures of human hepatocytes and human hepatoma HepG2 cells grown as monolayer or spheroids. Gene reporter assays showed that palmatine significantly activated the aryl hydrocarbon receptor (AhR) and increased the activity of CYP1A1 gene promoter in transiently transfected HepG2 cells. In HepG2 monolayer culture, palmatine also significantly increased mRNA and activity levels of CYP1A1, albeit with considerably less potency than 2,3,7,8-tetrachlorodibenzo-p-dioxin, a prototypical CYP1A inducer. On the other hand, CYP1A activity was not significantly elevated by palmatine in HepG2 spheroids. Moreover, palmatine induced mild or negligible changes in CYP1A1 and CYP1A2 mRNA expression without affecting CYP1A activity levels in primary human hepatocytes. It is concluded that palmatine activates the AhR-CYP1A pathway in HepG2 monolayer, while the potential for CYP1A induction is irrelevant in cell systems which are closer to the in vivo situation, i.e. in HepG2 spheroids and primary cultures of human hepatocytes. Possible induction of CYP1A enzymes by palmatine in vivo remains to be investigated.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, Olomouc 77515, Czech Republic. Electronic address: vrbambv@seznam.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Vrba
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, Olomouc 77515, Czech Republic.
authors.forename: Marika
authors.initials: M
authors.lastname: Havlikova
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, Olomouc 77515, Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Gerhardova
authors.affiliation: Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, Olomouc 77515, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, Olomouc 77515, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichova
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D001599:Berberine / Q000737:chemistry / Q000494:pharmacology; D001600:Berberine Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001599:Berberine; D001600:Berberine Alkaloids; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D018336:Receptors, Aryl Hydrocarbon; C111235:AHR protein, human; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; C005413:palmatine
keywords: Alkaloid; Aryl hydrocarbon receptor; CYP1A1; Cytochrome P450; Herb–drug interactions; Palmatine