Safety of Herbal Medicinal Products: Echinacea and Selected Alkylamides Do Not Induce CYP3A4 mRNA Expression

Figure 1

The control of CYP protein levels by HMP. Components of the HMP can either bind the AhR and CAR causing their translocation to the nucleus, or bind the inactive PXR in the nucleus and activate it. Following this binding step, AhR/CAR and PXR can initiate a sequence of events that increases CYP mRNA production and consequently increased CYP protein production. Increased CYP protein levels can accelerate drug metabolism, pro-drug activation and bioactivation. CYP3A4 transcription is mainly controlled by PXR. Increase in mRNA levels can be detected by quantification with real time RT-PCR. Another possibility is that HMP components may also affect post translational modifications such as ubiquitination, which results in protein degradation. This can lead to a change in CYP protein levels without affecting mRNA levels.