Palmatine activates AhR and upregulates CYP1A activity in HepG2 cells but not in human hepatocytes
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24583342
DOI
10.1016/j.tiv.2014.02.008
PII: S0887-2333(14)00033-2
Knihovny.cz E-resources
- Keywords
- Alkaloid, Aryl hydrocarbon receptor, CYP1A1, Cytochrome P450, Herb–drug interactions, Palmatine,
- MeSH
- Berberine chemistry pharmacology MeSH
- Berberine Alkaloids chemistry pharmacology MeSH
- Hep G2 Cells MeSH
- Cytochrome P-450 CYP1A1 genetics metabolism MeSH
- Cytochrome P-450 CYP1A2 genetics metabolism MeSH
- Hepatocytes drug effects MeSH
- Humans MeSH
- Molecular Structure MeSH
- Receptors, Aryl Hydrocarbon genetics metabolism MeSH
- Gene Expression Regulation drug effects MeSH
- Basic Helix-Loop-Helix Transcription Factors genetics metabolism MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- AHR protein, human MeSH Browser
- Berberine MeSH
- Berberine Alkaloids MeSH
- CYP1A1 protein, human MeSH Browser
- CYP1A2 protein, human MeSH Browser
- Cytochrome P-450 CYP1A1 MeSH
- Cytochrome P-450 CYP1A2 MeSH
- palmatine MeSH Browser
- Receptors, Aryl Hydrocarbon MeSH
- Basic Helix-Loop-Helix Transcription Factors MeSH
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.
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