ASSESSING THE IMPACT OF PINEAPPLE AND POMEGRANATE JUICES ON IN VITRO CYP2C9-MEDIATED GLIMEPIRIDE METABOLISM

Abstract

The primary aim of this investigation was to assess the influence of pineapple and pomegranate juices on the CYP2C9-mediated metabolism of glimepiride. The study was centered on a comparative appraisal of the inhibitory effects of pineapple and pomegranate juices using human liver microsomes in vitro. To address this inquiry, the impact of pineapple and pomegranate juices on the metabolism of another CYP2C9 substrate, glimepiride, was scrutinized through the determination of inhibition constants (IC50) and exploration of their effect on Glimepiride's Michaelis-Menten kinetics employing human liver microsomes. Subsequent to the centrifugation of incubates, samples were injected into the HPLC system, and quantification was executed by evaluating the UV peak areas at 228nm. Notably, pineapple juice emerged as a potent inhibitor of human CYP2C9 in comparison to pomegranate juice. In human liver microsomes, the average IC50 values for pineapple juice (PIJ) and pomegranate juice (POJ) concerning CYP (glimepiride hydroxylation) were identified as 1.62 ± 0.273 µl and 3.08 ± 0.388 µl, respectively. The findings obtained from in vitro experiments indicated the competitive nature of inhibition, evident from the elevated Km values (47.50 µMole) and mostly unaltered Vmax (0.492 µMole/min/mg protein) when treated with pineapple juice. A parallel observation was made for pomegranate juice, where Km increased (34.00µMole) and Vmax remained mostly unaffected (0.509µMole/min/mg protein). In essence, this study revealed modifications in the metabolism of glimepiride instigated by pineapple and pomegranate juices. Amidst the fruits subjected to evaluation, pineapple juice displayed robust inhibition of CYP2C9 activity, whereas pomegranate juice exhibited a marginal impact on the oxidative metabolism of glimepiride.