title: Aloe vera juice: IC₅₀ and dual mechanistic inhibition of CYP3A4 and CYP2D6.
abstract: The aim of this study was to evaluate the inhibitory potency (IC₅₀ values) of ethanol extracts of two commercially available aloe vera juice (AVJ) products, on CYP3A4 and CYP2D6 activities in vitro and to determine if such inhibitions could be mechanism-based. Recombinant human CYP3A4 and CYP2D6 enzymes were used and the activities were expressed by the metabolism of testosterone and dextromethorphan with ketoconazole and quinidine as positive inhibitor controls, respectively. The formed metabolites were quantified by validated HPLC techniques. Time- and NADPH- dependent inhibition assays were performed to evaluate a possible mechanism-based inhibition. One of the AVJ extracts showed about twice the inhibitory potency towards both CYP enzymes over the other with IC₅₀ values of 8.35 ± 0.72 and 12.5 ± 2.1 mg/mL for CYP3A4 and CYP2D6, respectively. The AVJ was found to exert both CYP mediated and non-CYP mediated inhibition of both CYP3A4 and CYP2D6. This dual mechanistic inhibition, however, seems to be governed by different mechanisms for CYP3A4 and CYP2D6. Estimated IC₅₀ inhibition values indicate no major interference of AVJ with drug metabolism in man, but the dual mechanistic inhibition of both enzymes might be of clinical significance.
authors.affiliation: Norwegian University of Science and Technology-Cancer Research and Molecular Medicine, Trondheim, Norway. ane.djuv@gmail.com
authors.forename: Ane
authors.initials: A
authors.lastname: Djuv
authors.forename: Odd Georg
authors.initials: OG
authors.lastname: Nilsen
mesh_terms: D000504:Aloe / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D003915:Dextromethorphan / Q000494:pharmacology; D004789:Enzyme Activation; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D020128:Inhibitory Concentration 50; D009249:NADP / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; D000431:Ethanol; D013739:Testosterone; D009249:NADP; D003915:Dextromethorphan; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human