CYP450 activity inhibition by Guazuma ulmifolia and major phytochemical constituent, procyanidin β2 in vitro: assessing the potential for drug interactions

Research in Jamaica reports prevalence rates for medicinal plant use of 73%, with 27% concomitant use with pharmaceutical drugs, highlighting the importance of assessing potential plant-drug interactions in a region where little such work has been undertaken to date. This in vitro study aimed to undertake an initial assessment of the potential inhibitory impact of a standardized Guazuma ulmifolia aqueous bark extract (GUABE), against the activity of key drug-metabolizing cytochrome P450 enzymes (CYPs). GUABE is used across the Caribbean for a number of health conditions and, in Jamaica, often used in root tonics, a commonly consumed health beverage. Results indicated potent inhibitory activity against CYPs 1A2 and 3A4 (IC₅₀ = 5.2 and 6.7 µg/ml respectively) and moderate activity against CYPs 2C9, 2C19 and 2D6 (IC₅₀ = 10.8, 79.9 and 28.5 µg/ml respectively). HPLC analysis of GUABE identified procyanidin β2 (Pβ2) as the most abundant phytochemical present. Assessment of Pβ2 against the activity of CYPs 1A2 and 3A4 demonstrated moderate (IC₅₀ = 43.7 µM) and weak activity (IC₅₀ > 145.5 µM), respectively. Synergistic analysis, using isobologram and combination index analysis, indicated slight synergistic interaction between GUABE and Pβ2 for the inhibition of CYP1A2. Pβ2, whilst not solely responsible for the observed potency of GUABE against CYP1A2, appears to play a part through synergistic interaction with other phytochemicals present in the extract. The potent inhibition of CYPs 1A2 and 3A4 in vitro, provides a useful preliminary indication of the potential for adverse herb-drug interactions and warrants further in vivo and clinical studies.