CYP3A4-mediated Effects of Cranberry and Pomegranate juices on Alprazolam Pharmacodynamics

aims: To evaluate the pharmacodynamic interactions between alprazolam, cranberry, and pomegranate juices, focusing on their impact on behavioural and histological outcomes. background: Alprazolam, a widely prescribed anxiolytic, is primarily metabolised by the cytochrome P450 3A4 (CYP3A4) enzyme. Cranberry and pomegranate juices, commonly used for kidney stone management, are known CYP3A4 inhibitors, potentially altering alprazolam metabolism and efficacy. objective: To investigate the effects of cranberry and pomegranate juices on alprazolam’s pharmacodynamics using behavioural tests and histological analysis. method: Molecular docking studies using AutoDock Vina assessed the binding affinities of cranberry anthocyanins and pomegranate ellagic acid to CYP3A4, yielding binding energies of -9.2 and -9.3 kcal/mol, respectively. In vivo experiments were conducted on adult male Wistar albino rats, divided into five groups: control, alprazolam alone, and alprazolam co-administered with cranberry, pomegranate, or both juices. Behavioral analyses included the Elevated Plus Maze, Rotarod, and Y-Maze tests. Histological examination was performed to evaluate neurodegeneration. result: Behavioural tests revealed significant impairments in memory and motor coordination in juice co-administration groups compared to alprazolam-only and control groups. Histological analysis showed increased neuronal degeneration in co-administration groups, indicating a potential synergistic neurotoxic effect. conclusion: Cranberry and pomegranate juices may significantly alter alprazolam’s therapeutic profile by enhancing neurotoxicity and impairing cognitive and motor functions.