Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 18, 2005
Publication Date: June 7, 2005
Repository URL: http://www.ars.usda.gov/sp2UserFiles/Place/66210000/Reprint944.pdf
Citation: Manthey, J.A., Buslig, B.S. 2005. Furanocoumarins in grapefruit juice fractions. Journal of Agricultural and Food Chemistry. 53:5158-5163. Interpretive Summary: Grapefruit juices were fractionated and the fractions analyzed to determine the composition and structures of compounds suspected to interact with various prescription medications. The fractions rich in grapefruit juice pulp and pulp material were richest in the interactive compounds. Methods are given for the HPLC-MS analysis of these compounds.
Technical Abstract: Studies of the interactions between numerous prescription medications and grapefruit (Citrus paradisi Macf.)juice have led investigators to suggest that these interactions arise from inhibition by compounds in grapefruit juice of components of the cytochrome P450 (CYP) enzyme system, and the P-glycoprotein transporter protein (P-gp) in cells of the intestinal wall. The cytochrome P450 system, particularly the 3A4 isoform (CYP3A4), is responsible for drug metabolism, while the P-gp is involved in trans-intestinal efflux control of drugs administered. Current evidence implicates the involvement of linear furanocoumarins (FCs), particularly those related to bergamottin (5-[(3',7'-dimethyl-2',6'-octadienyl)-oxy]-psoralen). Yet, the exact mechanisms of inhibition, and the roles of specific compounds are still uncertain. To better understand these interactions, freshly extracted grapefruit juice was separated into 4 fractions, consisting of raw finished juice (~5% fine pulp), centrifuge retentate (~35% fine pulp), centrifuged supernatant (<1% pulp) and coarse finisher pulp. Measurements of the concentrations of the FCs in each of these fractions were achieved by HPLC-MS, and have consequently enabled us to determine the most practical sources of FCs for the preparative-scale isolations necessary for structure identifications and future in vitro and in vivo biotesting.