Cytochrome P450 2C19 inhibitory activity of common berry constituents

Sand, Philipp G.; Dreiseitel, Andrea; Stang, Martin Michael; Schreier, Peter; Oehme, Anett; Locher, Sanja; Hajak, Goeran

doi:10.1002/ptr.2910

Cited by 19 publications

(14 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is necessary to consider herb-drug interactions in order to use herbs safely (9,10,(35)(36)(37)(38)(39). The present study attempted to determine whether rosehip hot water extract inhibited CYP3A4 activity.…”

Section: Discussionmentioning

confidence: 98%

“…A phenomenon similar to this food-drug interaction can be generated between food and drugs. Indeed, it has previously been demonstrated that beverages and food, such as beer, red wine, black and herbal tea, garlic, spices, mace, nutmeg, fruit and fruit juice, tomato juice, and licorice root inhibited enzyme-mediated drug metabolism (9,10,(35)(36)(37)(38)(39). Although rosehip has been used as a food and as a traditional medicine (16), to the best of our knowledge, there is no evidence of an interaction between rosehip and CYP3A4-metabolizing drugs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rosehip inhibits xanthine oxidase activity and reduces serum urate levels in a mouse model of hyperuricemia

et al. 2017

View full text Add to dashboard Cite

Abstract. Rosehip, the fruit of Rosa canina L., has traditionally been used to treat urate metabolism disorders; however, its effects on such disorders have not been characterized in detail. Therefore, the present study investigated the effects of hot water, ethanol and ethyl acetate extracts of rosehip on xanthine oxidase (XO) activity in vitro. In addition, the serum urate lowering effects of the rosehip hot water extract in a mouse model of hyperuricemia (male ddY mice, which were intraperitoneally injected with potassium oxonate) were investigated. Furthermore, the influence of rosehip hot water extract on CYP3A4 activity, which is the most important drug-metabolizing enzyme from a herb-drug interaction perspective, was investigated. Rosehip extracts of hot water, ethanol and ethyl acetate inhibited XO activity [half maximal inhibitory concentration (IC 50 ) values: 259.6±50.6, 242.5±46.2 and 1,462.8±544.2 µg/ml, respectively]. Furthermore, the administration of 1X rosehip hot water extract significantly reduced the levels of serum urate at 8 h, which was similar when compared with the administration of 1 mg/kg allopurinol. Rosehip hot water extract only marginally affected CYP3A4 activity (IC 50 value, >1 mg/ml). These findings indicate that rosehip hot water extract may present as a functional food for individuals with a high urate level, and as a therapeutic reagent for hyperuricemic patients.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Rosehip inhibits xanthine oxidase activity and reduces serum urate levels in a mouse model of hyperuricemia

et al. 2017

View full text Add to dashboard Cite

show abstract

“…There is a dearth of information on the pharmacokinetics properties of phytochemicals from herbs; especially the human oral bioavailability of these herbal components. Few studies available indicates oral bioavailability for anthocyanin, flavonoids and saponins, with the anthocyanins and flavonoids having short half lives (Wu et al, 2002;Yu et al, 2012) In vitro studies have shown that some phytochemicals namely coumarins, saponins, flavonoids and anthocyanins have inhibitory activities on CYP isoforms (Kim et al, 1997;Kimura et al, 2010;Sand et al, 2010). These compounds which are also present in the calyx of Hibiscus sabdariffa might have been responsible for the observed inhibitory activities of the extract.…”

Section: Discussionmentioning

confidence: 99%

<i>In vitro</i> inhibitory activities of the extract of <i>Hibiscus sabdariffa</i> L. (family malvaceae) on selected cytochrome p450 isoforms

Johnson

Oyelola²,

Tolonen³

et al. 2013

Afr. J. Trad. Compl. Alt. Med.

View full text Add to dashboard Cite

Literature is scanty on the interaction potential of Hibiscus sabdariffa L., plant extract with other drugs and the affected targets. This study was conducted to investigate the cytochrome P450 (CYP) isoforms that are inhibited by the extract of Hibiscus sabdariffa L. in vitro. The inhibition towards the major drug metabolizing CYP isoforms by the plant extract were estimated in human liver microsomal incubations, by monitoring the CYP-specific model reactions through previously validated N-in-one assay method. The ethanolic extract of Hibiscus sabdariffa showed inhibitory activities against nine selected CYP isoforms: CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. The concentrations of the extract which produced 50% inhibition of the CYP isoforms ranged from 306 µg/ml to 1660 µg/ml, and the degree of inhibition based on the IC 50 values for each CYP isoform was in the following order: CYP1A2 > CYP2C8 > CYP2D6 > CYP2B6 > CYP2E1 > CYP2C19 > CYP3A4 >> CYP2C9 >> CYP2A6. Ethanolic extract of Hibiscus sabdariffa caused inhibition of CYP isoforms in vitro. These observed inhibitions may not cause clinically significant herb-drug interactions; however, caution may need to be taken in co-administering the water extract of Hibiscus sabdariffa with other drugs until clinical studies are available to further clarify these findings.Key words: Cytochrome P450, Hibiscus sabdariffa, Herb-drug interaction, Anthocyanin, N-in-one assay. List of non-standard abbreviations: TMA -Total Monomeric Anthocyanin, EEHS -ethanolic extract of Hibiscus sabdariffa, EAR -Enzyme activity remaining. IntroductionHerbal remedies have been in use over the ages until synthetic drugs became available, however, there has been resurgence in the use of herbal remedies. This resurgence has led to increase in the concomitant use of herbs with conventional medicines with the belief that the potency of either the herb or the conventional medicine may be enhanced. But the concomitant use of herbs with conventional medicines has given rise to various potential interactions which may not be beneficial to the user. For example Ginkgo biloba causes spontaneous bleeding when co-administered with aspirin, ibuprofen or warfarin (Bressler, 2005). Panax ginseng induces mania when used with phenelzine and St. John's Wort reduces the plasma concentrations of midazolam, digoxin and indinavir (Hu et al., 2005).Some of these potential herb-drug interactions occur when the pharmacokinetic profile of either product is altered significantly as a result of their co-administration. However most interactions occur during metabolism especially phase 1 metabolism which is mediated by cytochrome P450 (CYP) isoforms. CYP isoforms are responsible for the metabolism of about 70% of prescription drugs (Karyekar et al., 2002). The induction or inhibition of CYP isoforms by any of the product of herb and drug combination may lead to increased side effect, toxicity or therapeutic failure. Many CYP isoforms such as CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2...

show abstract

“…[2][3][4] In vitro screening assays with beverages and foods such as beer, red wine, black and herbal tea, garlic, spices, mace, nutmeg, fruits, and fruit juices have all shown the ability to inhibit enzyme-mediated drug metabolism. [5][6][7][8][9][10] CYP3A4 is the most important drug metabolizing enzyme, in that it metabolizes more than 50% of all clinical drugs.11) It is expressed as the most abundant constituent in the human liver CYP enzyme system 12) and is also expressed at substantial levels in the intestinal epithelial cells to metabolize and limit absorption of orally administered CYP3A4 substrate drugs.13) Grapefruit juice is an extensively studied dietary substance that is shown to irreversibly inhibit enteric CYP3A in a mechanism-based manner. [14][15][16] Mechanism-based inhibition (MBI) of CYP3A4 is characterized by nicotinamide adenine dinucleotide phosphate (NADPH)-, time-, and concentration-dependent enzyme inactivation that occurs when some substrates are converted by CYPs into reactive metabolites.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Mechanism-Based Inhibition of Recombinant Human Cytochrome P450 3A4 by Tomato Juice Extract

Sunaga

Ohkawa

Nakamura

et al. 2012

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

This study investigates whether tomato juice can inhibit cytochrome P450 (CYP) 3A4-mediated drug metabolism. Three commercially available, additive-free tomato juices, along with homogenized fresh tomato, were analyzed for their ability to inhibit testosterone 6β-hydroxylation activity using human recombinant CYP3A4. Results were compared to that of grapefruit juice. Ethyl acetate extracts of the tomato juices moderately reduced residual activity of CYP3A4 testosterone 6β-hydroxylation activity by 19.3-26.2% with 0-min preincubation. Residual activity was strongly reduced by 69.9-83.5% at 20-min preincubation, a reduction similar to that of grapefruit juice extract, known to contain constituents of mechanism-based inhibitors. One juice extract (tomato juice C) showed irreversible dose-and preincubation time-dependent and partial nicotinamide adenine dinucleotide phosphate (NADPH)-dependent inhibition of CYP3A4 activity. Furthermore, we examined whether the CYP3A4 inhibitory effect of tomato juice was substrate dependent by examining midazolam 1′-hydroxylation activity and nifedipine oxidation activity, in addition to testosterone 6β-hydroxylation activity. Tomato juice showed a potent inhibitory effect on nifedipine oxidation activity, which was comparable to that on testosterone 6β-hydroxylation activity; however, it showed a weak inhibitory effect on midazolam 1′-hydroxylation activity. We conclude that tomato juice contains one or more mechanism-based and competitive inhibitor(s) of CYP3A4. Additionally, significant CYP3A4 inhibitory activity did not result from lycopene, a major compound in tomato. Although the active compound was uncertain, a strong CYP3A4 inhibitory activity was observed in other solanaceous plants, i.e., potato, eggplant, sweet pepper, and capsicum. Therefore, responsible compounds in tomato are likely commonly shared among solanaceous vegetables.Key words tomato juice; mechanism-based inhibition; food-drug interaction; human recombinant cytochrome P450 3A4 Many foods and/or beverages have recently been found to influence drug metabolism or transport, sometimes resulting in clinically important drug interactions. This food-drug interaction is a critical aspect of pharmacotherapy. Food-drug interaction can be viewed in terms of pharmacokinetics and pharmacodynamics. Pharmacokinetic interactions can involve enzymes and transporters that are implicated in drug absorption, distribution, metabolism, or excretion. Pharmacodynamic interactions involve the pharmacological effect of a drug or physiologic effect of a dietary constituent. 1)Foods that inhibit drug metabolism enzymes, such as cytochrome P450 (CYP), elevate the blood concentration of co-administered drugs, resulting in a food-drug interaction, which sometimes causes adverse effects. [2][3][4] In vitro screening assays with beverages and foods such as beer, red wine, black and herbal tea, garlic, spices, mace, nutmeg, fruits, and fruit juices have all shown the ability to inhibit enzyme-mediated drug metabolism. [5][6][7][8][9][10] CYP...

show abstract

Cytochrome P450 2C19 inhibitory activity of common berry constituents

Cited by 19 publications

References 26 publications

Rosehip inhibits xanthine oxidase activity and reduces serum urate levels in a mouse model of hyperuricemia

Rosehip inhibits xanthine oxidase activity and reduces serum urate levels in a mouse model of hyperuricemia

<i>In vitro</i> inhibitory activities of the extract of <i>Hibiscus sabdariffa</i> L. (family malvaceae) on selected cytochrome p450 isoforms

Mechanism-Based Inhibition of Recombinant Human Cytochrome P450 3A4 by Tomato Juice Extract

Contact Info

Product

Resources

About