Highly sensitive solid forms discrimination on the whole tablet of the active ingredients in quercetin dietary supplements by NMR crystallography approaches

Miclăuş, Maria; Filip, Xenia; Filip, Claudiu; Martin, Flavia; Grosu, Ioana Georgeta

doi:10.1016/j.jpba.2016.03.006

Cited by 12 publications

(16 citation statements)

References 24 publications

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“…It is widely present in vegetables (including onions and broccoli), fruits (including apples, grapes and berry crops), certain herbs, tea and wine ( 1 ). It is marketed as a dietary supplement ( 2 ). Onions are the primary source of dietary quercetin (up to 1.2 g/kg fresh weight) in numerous countries ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Quercetin‑3‑O‑β‑D‑glucoside decreases the bioavailability of cyclosporin A through regulation of drug metabolizing enzymes, transporters and nuclear receptors in rats

et al. 2018

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Quercetin is a flavonoid compound that is widely present in food and drink. Quercetin-3-O-β-D-glucoside (Q3GA) is a major metabolite of quercetin. The aim of the present study was to investigate the effect of Q3GA on the pharmacokinetics of orally and intravenously administered cyclosporin A (CsA) in rats, and to assess the effect of Q3GA on drug-metabolizing enzymes (DMEs), drug transporters (DTs) and nuclear receptors (NRs). The pharmacokinetic parameters of CsA were measured following oral (10 mg/kg) and intravenous (2.5 mg/kg) administration of CsA in the presence or absence of Q3GA. The mRNA and protein expression levels of DMEs, DTs and NRs in the liver and small intestine were detected by quantitative polymerase chain reaction and western blot analysis. The results indicated that the intravenous administration of Q3GA (2.5, 5 or 10 mg/kg) for 7 consecutive days reduced the bioavailability of oral CsA. By contrast, the pharmacokinetics of the intravenous administration of CsA were not affected by Q3GA. However, the mRNA and protein expression levels of DMEs and DTs were inhibited by Q3GA. The activation of DMEs and DTs by NRs, and the interplay between DMEs and DTs, may explain these results. The present study identified a novel flavonoid-drug interaction, which may have implications for patients taking CsA and quercetin supplements or on a quercetin-containing diet.

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Section: Introductionmentioning

confidence: 99%

Quercetin‑3‑O‑β‑D‑glucoside decreases the bioavailability of cyclosporin A through regulation of drug metabolizing enzymes, transporters and nuclear receptors in rats

et al. 2018

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“…In recent years, dietary supplements and alternative medicine therapies have become increasingly accepted. A previous study ( 38 ) has demonstrated that the absorption and disposition of the active ingredients of dietary supplements are significant in determining their biological activity. In addition, accumulated evidence with regard to HDIs between drug-metabolizing enzymes and drug transporters may be used to predict the pharmacokinetic profile of drugs and the underlying HDIs ( 39 , 40 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of quercetin and its major metabolite quercetin‑3‑O‑β‑D‑glucoside on human UDP‑glucuronosyltransferase 1A isoforms by liquid chromatography‑tandem mass spectrometry

Zhang

Yang

et al. 2021

Exp Ther Med

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Quercetin is a flavonoid that is widely present in plant-derived food. Quercetin-3-O-β-D-glucoside (Q3GA) is a predominant metabolite of quercetin in animal and human plasma. The inhibitory effects of the UDP-glucuronosyl transferases (UGTs) caused by herbal components may be a key factor for the clinical assessment of herb-drug interactions (HDIs). The present study aimed to investigate the inhibitory profile of quercetin and Q3GA on recombinant UGT1A isoforms in vitro . The metabolism of the nonspecific substrate 4-methylumbelliferone (4-MU) by the UGT1A isoforms was assessed by liquid chromatography-tandem mass spectrometry. Preliminary screening experiments indicated that quercetin exhibited stronger inhibitory effects on UGT1A1, UGT1A3, UGT1A6 and UGT1A9 enzymes than Q3GA. Kinetic experiments were performed to characterize the type of inhibition caused by quercetin and Q3GA towards these UGT isoforms. Quercetin exerted non-competitive inhibition on UGT1A1 and UGT1A6, with half maximal inhibitory concentration (IC 50 ) values of 7.47 and 7.07 µM and inhibition kinetic parameter (K i ) values of 2.18 and 28.87 µM, respectively. Quercetin also exhibited competitive inhibition on UGT1A3 and UGT1A9, with IC 50 values of 10.58 and 2.81 µM and K i values of 1.60 and 0.51 µM, respectively. However, Q3GA displayed weak inhibition on UGT1A1, UGT1A3 and UGT1A6 enzymes with IC 50 values of 45.21, 106.5 and 51.37 µM, respectively. In the present study, quercetin was a moderate inhibitor of UGT1A1 and UGT1A3, a weak inhibitor of UGT1A6, and a strong inhibitor on UGT1A9. The results of the present study suggested potential HDIs that may occur following quercetin co-administration with drugs that are mainly metabolized by UGT1A1, UGT1A3 and UGT1A9 enzymes.

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“…In the following, we show that the same general considerations apply also when characterizing any hydrogen bond that may form in organic solids, whether it implies proton transfer or not. We illustrate this statement with the example of various solid forms of Quercetin, a naturally occurring flavonoid intensively studied in our group [ 84 , 85 , 86 , 87 ]. As can be seen from the molecular structure of Quercetin, the crystal structure determination from powder should not be a difficult task, because there is only one flexible torsion angle, denoted by θ 1 in Figure 7 a, that must be adjusted for structure refinement.…”

Section: With or Without Transfer There Is Definitely Sharingmentioning

confidence: 99%

“…This covers also the problem of better locating labile hydrogen atoms, with real benefits for crystal engineering approaches aimed at developing materials with tailored functionalities based on the directional and reversible character of hydrogen bonding. Although a precision limit that could be generally guaranteed in any case is not possible to be defined, the numerous examples in the literature [ 67 ], including the systems investigated in our research group that are discussed in more details below [ 59 , 82 , 84 , 85 , 86 , 87 ], clearly illustrates the state-of-the-art reached by NMR crystallography in characterizing hydrogen-mediated noncovalent interactions. In fact, as most of these studies reveal, the power of this technique comes from the fact that potential ambiguities of the PXRD structural models, or limitations in the DFT geometry optimization, can be easily identified and corrected in practice via the analysis of the numerous ss-NMR experimental parameters that are sensitive to the interactions experienced by 1 H nuclei.…”

Section: How Accurate Can Hydrogen Atoms Position Be Constrained Bmentioning

confidence: 99%

“…Only the model with the lowest energy is considered finally for all-atoms DFT geometry optimization, which leads also to the desired computational time savings. The reliability of the new approach was demonstrated [ 85 ] on quercetin dihydrate and anhydrous quercetin, two solid forms with known crystal structure, and then also successfully applied to the crystal structure determination of other new quercetin solid forms [ 86 , 87 ].…”

Section: With or Without Transfer There Is Definitely Sharingmentioning

confidence: 99%

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Hydrogen-Mediated Noncovalent Interactions in Solids: What Can NMR Crystallography Tell About?

et al. 2020

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Hydrogen atoms play a crucial role in the aggregation of organic (bio)molecules through diverse number of noncovalent interactions that they mediate, such as electrostatic in proton transfer systems, hydrogen bonding, and CH–π interactions, to mention only the most prominent. To identify and adequately describe such low-energy interactions, increasingly sensitive methods have been developed over time, among which quantum chemical computations have witnessed impressive advances in recent years. For reaching the present state-of-the-art, computations had to rely on a pool of relevant experimental data, needed at least for validation, if not also for other purposes. In the case of molecular crystals, the best illustration for the synergy between computations and experiment is given by the so-called NMR crystallography approach. Originally designed to increase the confidence level in crystal structure determination of organic compounds from powders, NMR crystallography is able now to offer also a wealth of information regarding the noncovalent interactions that drive molecules to pack in a given crystalline pattern or another. This is particularly true for the noncovalent interactions which depend on the exact location of labile hydrogen atoms in the system: in such cases, NMR crystallography represents a valuable characterization tool, in some cases complementing even the standard single-crystal X-ray diffraction technique. A concise introduction in the field is made in this mini-review, which is aimed at providing a comprehensive picture with respect to the current accuracy level reached by NMR crystallography in the characterization of hydrogen-mediated noncovalent interactions in organic solids. Different types of practical applications are illustrated with the example of molecular crystals studied by our research group, but references to other representative developments reported in the literature are also made. By summarizing the major concepts and methodological progresses, the present work is also intended to be a guide to the practical potential of this relatively recent analytical tool for the scientists working in areas where crystal engineering represents the main approach for rational design of novel materials.

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Highly sensitive solid forms discrimination on the whole tablet of the active ingredients in quercetin dietary supplements by NMR crystallography approaches

Cited by 12 publications

References 24 publications

Quercetin‑3‑O‑β‑D‑glucoside decreases the bioavailability of cyclosporin A through regulation of drug metabolizing enzymes, transporters and nuclear receptors in rats

Quercetin‑3‑O‑β‑D‑glucoside decreases the bioavailability of cyclosporin A through regulation of drug metabolizing enzymes, transporters and nuclear receptors in rats

Inhibitory effects of quercetin and its major metabolite quercetin‑3‑O‑β‑D‑glucoside on human UDP‑glucuronosyltransferase 1A isoforms by liquid chromatography‑tandem mass spectrometry

Hydrogen-Mediated Noncovalent Interactions in Solids: What Can NMR Crystallography Tell About?

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