Harmane Inhibits Hepatic Cytochrome P450 Enzymes in Rats
Authors
Klaskova, E., Zendulka, O., Pes, O., Eyrilmez, S. M., Bednar, D., Jurica, J.
Source
FRONTIERS IN PHARMACOLOGY X: xxx-xxx (2026)
Abstract
Harmane (HAR) is a beta-carboline alkaloid found in plants, heat-processed foods and tobacco. It is an active component of broadly used antidepressant and anxiolytic herbs. This study investigates HAR’s effects on rat CYP enzymes both in vivo and in vitro, and examines its interactions with human CYP enzymes through in silico methods. Impact of subchronic premedication with HAR at the doses 25, 40 and 64 mg/kg on CYP enzyme activity was evaluated in rats using CYP-specific probe substrates of CYP1A2, CYP2A, CYP2B, CYP2C6, CYP2C11, CYP2D1/2 and CYP3A1/2. In vitro inhibitory assays of HAR were conducted. Finally, HAR was docked in silico into human CYP enzyme active sites. HAR premedication significantly decreased rat CYP2B1, CYP2C11, CYP2D1/2, and CYP3A1/2 protein content and metabolic activity. In vitro, HAR showed moderate inhibition of CYP2A1 and CYP3A1/2 (IC50 14.0 and 1.2 µM, respectively) and no inhibition of the other enzymes tested. In silico docking studies with human CYP enzymes confirmed HAR potential for CYP-mediated drug-drug inhibitory interactions. In summary, HAR significantly inhibited several drug-metabolizing CYP enzyme activities in preclinical model. These findings suggest a need for further research into HAR’s pharmacokinetic interactions.