Inhibitory Effects of Vegetable Juices on CYP3A4 Activity in Recombinant CYP3A4 and LS180 Cells

Abstract

It is thought that eating habits induces individual variation in intestinal absorption® ; KAGOME Co., Ltd., Aichi, Japan) were centrifuged (1630 g, 10 min) and filtered using filter paper and 0.45-µm membrane filters. In this study, recombinant CYP3A4 and LS180 cells were used for the evaluation of CYP3A4 activity. The metabolisms to 6β-hydroxytestosterone by recombinant CYP3A4 were significantly inhibited by VJ-o, VJ-g, and VJ-y in a preincubation time-dependent manner, and CYP3A4 activity in LS180 cells were significantly inhibited by VJ-o and VJ-y. These results show that the difference in ingestion volume of vegetable juices and vegetables might partially induce individual difference in intestinal drug metabolism.

Contributors to the substantial variation in on‐treatment testosterone levels in men receiving transdermal testosterone gels in randomized trials

“…The copy number variation (CNV) was treated like a SNP; 0 repeats vs. 1 repeat vs. 2 repeats. The CAG AR repeat analysis was represented by a discrete variable assuming three levels according to whether the number of repeats is less than or equal to 20 (≤20), between 21 and 26 (Benjamini & Hochberg, ; Wang et al ., ; Salameh et al ., ; Azur et al ., ; Bhasin et al ., ; Tsujimoto et al ., ) or larger than or equal to 27 (≥27). Association between each of the variables of interest and the number of CAG repeats was evaluated by testing the null hypothesis that the fixed effect for all three levels of the CAG repeats (≤20, 21–26, ≥27) is equal.…”

Inhibitory Effects of Juices Prepared from Individual Vegetables on CYP3A4 Activity in Recombinant CYP3A4 and LS180 Cells

“…Orange vegetable juices strongly inhibited CYP3A4 activity compared to other vegetable juices, but the inhibition was slightly time-dependent during preincubation. 9) In addition, quercetin is known to be a reversible inhibitor of CYP3A4 activity. 15) Therefore, quercetin contained in onion may be considered to be a major inhibitory component in the mixture of orange vegetables juices.…”

“…9) In addition, the 6β-hydroxytestosterone assay was conducted using the HPLC-UV method, as previously reported by us. 9) Detection of CYP3A4 Activity in LS180 Cells Using the P450-Glo-Assay Kit Human colon adenocarcinoma LS180 cells (American Type Culture Collection, Manassas, VA, U.S.A.) were selected for in vitro evaluation of CYP3A4 activity. CYP3A4 activity was measured using the P450-Glo assay (Luciferin-IPA selectively reacts with CYP3A4 and hardly reacts with CYP3A5 and CYP3A7: Promega, Madison, WI, U.S.A.), as previously reported by us.…”

“…CYP3A4 activity was measured using the P450-Glo assay (Luciferin-IPA selectively reacts with CYP3A4 and hardly reacts with CYP3A5 and CYP3A7: Promega, Madison, WI, U.S.A.), as previously reported by us. 9) Estimation of Pharmacokinetic Parameters To calculate the pharmacokinetic parameters, namely, the Michaelis constant (K m ), maximum velocity (V max ), and IC 50 , of testosterone metabolism by human recombinant CYP3A4, Eqs. 1 and 2 were fitted to the observed data by non-linear least-squares regression analysis with the MULTI program 13) :…”

“…9) Juices prepared using orange, green, and yellow vegetables, including bell pepper, cabbage, carrot, Chinese cabbage, eggplant, Japanese radish, and lettuce, strongly inhibited CYP3A4 activity. These vegetables contain various flavonoids such as kaempferol and quercetin that can inhibit CYP3A4 activity.…”