Plumbagin and Plumbago indica Differentially Modulated Cytochrome P450 and Transporter Profiles in BeWo and HepG2 Cells.

Background and Objective: The medicinal herb Plumbago indica (PI) and its major constituent plumbagin have reported pharmacological properties but there is a lack of information about their herb-drug interactions. The effects of methanolic (PI-MeOH) and ethanolic (PI-EtOH) crude extracts of PI and plumbagin on the expression of cytochrome P450s (CYP1A2, CYP2E1 and CYP3A4) and transporters (ABCC1, ABCG2 and SLC22A11) were investigated in BeWo and HepG2 cells. Materials and Methods: BeWo or HepG2 cells were treated with 0.5-5 μM plumbagin or 25-500 μg mL1 of PI-MeOH or PI-EtOH for 24 hrs. Total RNA was extracted and mRNA expression of CYPs and transporters were determined using RT-qPCR. Results: PI and plumbagin affected mRNA expression differently in the two tested cell types. In BeWo cells, all concentrations of PI-MeOH induced CYP2E1, 100 and 500 μg Ml1 PI-MeOH and PI-EtOH up-regulated CYP1A2, CYP3A4 and ABCG2 and 500 μg mL1 PI-EtOH induced ABCG2 expression. Plumbagin suppressed CYP1A2 and induced SLC22A11 expression at the highest concentration, 5 μM. In HepG2 cells, 5 μM plumbagin and 500 μg Ml1 PI-EtOH suppressed CYP3A4 expression and 500 μg mL1 PI-MeOH and PI-EtOH up-regulated CYP1A2 and CYP2E1 expression. ABCC1 expression was induced by all treatments while ABCG2 and SLC22A11 were induced only by 500 μg mL1 PI-MeOH and PI-EtOH. Conclusion: The use of PI or plumbagin supplements in large quantities or for long periods should be carefully considered due to the risk of herbal drug interactions via modulated expression of CYPs and transporters.