The Inhibitory Effect Of Red Wine Component Gallic Acid On CYP3A4-mediated Nifedipine Metabolism In Vitro

Red Wine has the effect of preventing cardiovascular disease.Manypatients with hypertension drink wine to assist drug treatment ofhypertension. Nifedipine is the best-selling anti-hypertensive drug in china,which almost metabolized by CYP3A4in liver. The high probability ofco-administration of nifedipine and red wine, there is potential risk forfood-drug interactions.The inhibitory effect and mechanism of red wine acidic phenol extracton CYP3A4on rat liver microsomes (RLM), human liver microsomes(HLM) and recombinant CYP3A4enzyme was investigated in vitro. Theresults show that red wine acidic phenol extract inhibit the activity ofCYP3A4, obviously. Gallic acid exhibits irreversible inhibition onCYP3A4. Gallic oxidation product of acid, produced through non-NADPHpathway shows a stronger inhibition effect than gallic acid.This paper also studied the effects of extracts of red wine and gallicacid on the metabolism of nifedipine in vitro. The results show that redwine acidic phenol extract inhibit the metabolism of nifedipine by reducingthe affinity of CYP3A4and nifedipine. The possible mechanism was gallic acid combined with CYP3A4-related sites, firstly. This combination mayreduce the affinity of CYP3A4and nifedipine, but this combination isreversible. However, the inhibitory effect of gallic acid oxidation productswas not mediated by reducing the affinity of CYP3A4and nifedipine,which may be ascribe to affect the three-dimensional structure of CYP3A4.The red wine extract, gallic acid and gallic acid oxidation products couldreduce the metabolic clearance rate of nifedipine, significantly.In short, the ingredients in red wine and gallic acid can be reduced themetabolism of nifedipine by inhibiting the activity of CYP3A4. This workoffers a useful reference for the reasonable and safe use of natural productsto avoid unnecessary food-drug interactions.