Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1

Wang YM, Lin W, Chai SC, Wu J, Ong SS, Schuetz EG, Chen T · Toxicology and Applied Pharmacology

Piperine binds and activates the pregnane X receptor and thereby induces CYP3A4 and MDR1 — the opposite direction to the inhibition it shows in short-term assays. The authors call the dichotomy a challenge to piperine's use as a bioavailability enhancer.

Population

Human hepatocytes and intestinal cells, plus a mouse model

Intervention

Piperine

Comparator

Vehicle control

Limitations

Cell and mouse work; whether chronic supplemental piperine induces CYP3A4 in people has not been measured, so the direction of any long-term interaction is unresolved rather than benign.