Palmatine activates AhR and upregulates CYP1A activity in HepG2 cells but not in human hepatocytes.

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.