Major furocoumarins in grapefruit juice II: Phototoxicity, photogenotoxicity, and inhibitory potency vs. cytochrome P450 3A4 activity

Messer, Anastasia; Raquet, Nicole; Löhr, Christiane V.; Schrenk, Dieter

doi:10.1016/j.fct.2011.11.023

Cited by 40 publications

(18 citation statements)

References 22 publications

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“…When lovastatin is administered with food, the intestinal absorption may be increased by about 50%, while pectin and oat bran may decrease its absorption [22-24]. The excessive use of grapefruit juice may inhibit CYP3A4 and lead to higher plasma concentrations of lovastatin [25,26]. …”

Section: Introductionmentioning

confidence: 99%

NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

et al. 2012

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BackgroundRed yeast rice (i.e., rice fermented with Monascus spp.), as a food supplement, is claimed to be blood cholesterol-lowering. The red yeast rice constituent monacolin K, also known as lovastatin, is an inhibitor of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase. This article aims to develop a sensitive nuclear magnetic resonance (NMR) method to determine the total statin content of red yeast rice products.MethodsThe total statin content was determined by a 400 MHz 1H NMR spectroscopic method, based on the integration of the multiplet at δ 5.37-5.32 ppm of a hydrogen at the hexahydronaphthalene moiety in comparison to an external calibration with lovastatin. The activity of HMG-CoA reductase was measured by a commercial spectrophotometric assay kit.ResultsThe NMR detection limit for total statins was 6 mg/L (equivalent to 0.3 mg/capsule, if two capsules are dissolved in 50 mL ethanol). The relative standard deviations were consistently lower than 11%. The total statin concentrations of five red yeast rice supplements were between 1.5 and 25.2 mg per specified daily dose. A dose-dependent inhibition of the HMG-CoA reductase enzyme activity by the red yeast rice products was demonstrated.ConclusionA simple and direct NMR assay was developed to determine the total statin content in red yeast rice. The assay can be applied for the determination of statin content for the regulatory control of red yeast rice products.

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Section: Introductionmentioning

confidence: 99%

NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

et al. 2012

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“…Although the issue of furanocoumarin toxicity has not been specifically addressed with ashitaba, it should be noted that a number of furanocoumarins have been shown to be phototoxic and photogenotoxic in addition to interfering with drug metabolism by cytochrome P450 enzymes [48]. Ashitaba, as is typical with members of the Apiaceae family, contains bioactive furanocoumarins (25) and dihydrofuranocoumarin analogs (23,27).…”

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confidence: 99%

“…Ashitaba, as is typical with members of the Apiaceae family, contains bioactive furanocoumarins (25) and dihydrofuranocoumarin analogs (23,27). In fact, compound 25 has illustrated phototoxic and photogenotoxic effects in a number of studies [48,49]. An assessment by the Senate Commission on Food Safety reported that compound 25 and its isomer 8-methoxypsoralen are only weakly mutagenic in the absence of UV light, but in the presence of UV radiation, these compounds bind covalently to DNA in bacteria and yeasts, leading to genotoxic and mutagenic effects [49].…”

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confidence: 99%

A Review of the Medicinal Uses and Pharmacology of Ashitaba

Caesar

Cech

2016

Planta Med

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Medicinal plants are commonly employed for therapeutic purposes throughout the world. A recent National Health Interview Survey estimated that nearly 18 % of adults in the United States regularly took non-vitamin, non-mineral dietary supplements in 2012 [1]. Because of the popularity of herbal medicines, it is important to understand the chemical basis behind the purported activities of botanicals. Angelica, a member of the Apiaceae (Umbelliferae) family, is a large genus comprised of over 60 species. Members of the genus have been utilized as medicines across the world, most notably in Asia, to treat numerous ailments, including influenza, hepatitis, arthritis, indigestion, fever, and microbial infections [2]. An increasing number of studies are being conducted on a medicinally promising member of the genus, Angelica keiskei Koidzumi (Apiaceae), or ashitaba. This large leafy perennial plant native to the Pacific coast of Japan is used throughout Asia for its diuretic, laxative, stimulant, and galactagogue properties [3]. In the past decade, several active constituents representing chalcones, flavanones, and coumarins have been isolated and characterized from ashitaba, and several bioactiv-ities have been described. This review presents the current progress on ashitaba pharmacological studies, with a focus on isolated secondary metabolites, biological activity, toxicological data, and clinical relevance. Bioactive Metabolites Isolated from Ashitaba ! Chalcones Most of the literature on the bioactive metabolites from ashitaba concerns the diverse activity of various chalcones (l " Table 1 and Fig. 1), which are most abundant in the root bark of the plant [4]. Chalcones are formed from phenylpropanoid starter units, extended with three malonyl-CoA molecules. The resulting polyketide is folded by the enzyme chalcone synthase to promote Claisen condensations and subsequent enolizations [5]. Interestingly, the bioactive chalcones found in ashitaba are prenylated at the 5′-position (l " Fig. 1), indicating that these molecules have undergone multiple biosynthetic steps, travelling through the acetate, shikimate, and isoprenoid pathways.

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“…Concomitant intake of grapefruit (Citrus paradisii) or pomelo (Citrus grandis) has been demonstrated to increase the bioavailability of immunosuppressants [147,160,161]. Some components of these citrus fruits, bergamottin and naringenin responsible for the bitter taste, can inhibit the activities of CYP3A4 and CYP3A5 enzymes both in the intestinal wall and in the liver, resulting in significant reduction of first-pass metabolism of CYP3A substrates, including ciclosporin and tacrolimus [162][163][164]. Significant reduction of ciclosporin/tacrolimus doses is necessary to avoid the risk of nephrotoxicity or other adverse events associated with immunosuppressive therapy.…”

Section: Metabolic Drug Interactions Between Immunosuppressants and Hmentioning

confidence: 99%

Metabolic Drug Interactions with Immunosuppressants

Monostory¹

2018

Organ Donation and Transplantation - Current Status and Future Challenges

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Organ transplantation has become a routine clinical practice for patients with endstage disease of liver, kidney, heart, or lung. Although improved immunosuppressant therapy substantially contributes to the success of transplantation, clinicians continue to face challenges because of wide interindividual variations in blood concentrations resulting in subtherapeutic or supratherapeutic levels. Many undesired side-effects or therapeutic failure of immunosuppressants as a consequence are the results of differences or changes in drug metabolism. Considering genetic and nongenetic factors, such as co-medication, can refine the immunosuppressant therapy, facilitating personalized treatments to individual recipients. This review provides an up-to-date summary of functional polymorphisms of enzymes involved in the metabolism of immunosuppressants with low molecular weight and of the clinical significance of metabolic drug interactions between immunosuppressive agents and other drugs in therapeutic regimens of transplant recipients.

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Major furocoumarins in grapefruit juice II: Phototoxicity, photogenotoxicity, and inhibitory potency vs. cytochrome P450 3A4 activity

Cited by 40 publications

References 22 publications

NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

NMR evaluation of total statin content and HMG-CoA reductase inhibition in red yeast rice (Monascus spp.) food supplements

A Review of the Medicinal Uses and Pharmacology of Ashitaba

Metabolic Drug Interactions with Immunosuppressants

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