Assessment of extracts from red yeast rice for herb-drug interaction by in-vitro and in-vivo assays.
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ABSTRACT:
SUBMITTER: Fung WT
PROVIDER: S-EPMC3291881 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:Wine is an alcoholic beverage of complex composition obtained through the fermentation of grape must. The consumption of wine has already been associated with a multitude of beneficial effects due to its high polyphenolic content. In this study, four Greek emblematic wines from two red (i.e., Xinomavro and Agiorgitiko) and two white (i.e., Assyrtiko and Malagouzia) varieties were analyzed for the estimation of their antioxidant profiles. To address this question, we assessed their ability to scavenge both synthetic and endogenous free radicals, such as DPPH•, ABTS+•, OH•, O2-, their potential reducing power, and their antimutagenic and antigenotoxic properties. All varieties exhibited potent antioxidant activity, as indicated by the results of methods above, with the red wines appearing more effective than the white ones regarding antioxidant capacity. Our small-scale study is the first to reveal that these wine varieties may have the ability to scavenge the most reactive endogenous radicals. In the future, this finding must be accompanied by larger studies to fill a knowledge gap in the scientific literature concerning a holistic approach of the in vitro antioxidant action of plant polyphenolic compounds. Conclusively, we believe that wines possess high bioactivity that allow them to settle in the industry of food additives and medicinal products.
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Project description:Using a cell-based cytotoxicity assay three new cytotoxic azaphilones, including two stereoisomers and designated monapurones A-C (1-3), were isolated from the extract of Monascus purpureus-fermented rice (red yeast rice). Their structures were elucidated by detailed interpretation of spectroscopic and chemical data. The relative configurations were assigned on the basis of analysis of NOE data, and the absolute configurations were determined by direct comparison of their CD spectra with those of known azaphilones and chemical correlations. In the in vitro assays, monapurones A-C (1-3) showed selective cytotoxicity against human cancer cell line A549 with IC50 values of 3.8, 2.8 and 2.4 microM respectively, while exhibiting no significant toxicity to normal MRC-5 and WI-38 cells at the same concentration.
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Project description:Radix Glycyrrhizae (RG)-Radix Euphorbiae Pekinensis (REP) is a representative incompatible herbal pair of Eighteen Incompatible Medicaments (EIM) and has been disputed in clinical application for a long time. The present study was performed with the Madin-Darby canine kidney (MDCK) cell line using cell cytotoxicity assay, apoptosis detection, cell cycle measurement, reactive oxygen species (ROS) determination, and high content analysis (HCA) in combination with high-performance liquid chromatography (HPLC) fingerprint comparison to clarify whether RG and REP can be concomitantly used from the perspective of cytotoxicity, investigate the major correlated compounds, and elucidate the underlying mechanisms. The results showed that the toxicity of REP could be significantly enhanced through its concomitant use with RG in the ratio of 1 : 1, and this increased toxicity could be weakened with the further increased proportion of RG. 3,3'-di-O-methylellagic acid-4'-O-β-D-xylopyranoside (DEAX) and 3,3'-di-O-methylellagic acid (DEA) were shown to be mainly responsible for the toxicity induced by concomitant use of REP and RG. Both RG-REP decoctions and the above two compounds boosted cell apoptosis, cellular morphological change, ROS accumulation, and mitochondrial membrane potential (MMP) disruption. In conclusion, the incompatible use of RG and REP is conditionally established because of the bidirectional regulatory effect of RG, and the major compounds responsible for RG-REP incompatibility are DEAX and DEA, which result in toxicity through activation of mitochondria-dependent apoptosis induced by increased ROS production. This study provided a basis for understanding the incompatible use of RG and REP and the EIM theory.
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Project description:AimsRed yeast rice (RYR) is contained in dietary supplements for patients with dyslipidemia. RYR supplements contain monacolin K, which is chemically identical to lovastatin, a licensed drug with a well-known risk profile. We aim to describe the safety profile of RYR by analysing spontaneous reports of suspected adverse reactions (ARs).MethodsWithin the Italian Surveillance System of Natural Health Products, suspected ARs were collected and evaluated by a multidisciplinary group of experts to assess causality using the WHO-UMC system or the CIOMS/RUCAM score, for hepatic reactions. The public version of the WHO-Vigibase was also queried.ResultsFrom April 2002 to September 2015, out of 1261 total reports, 52 reports concerning 55 ARs to RYR dietary supplements were collected. ARs consisted in myalgia and/or increase in creatine phosphokinase (19), rhabdomyolysis (1), liver injury (10), gastrointestinal reactions (12), cutaneous reactions (9) and other reactions (4). Women were involved in 70% of cases. In 13 cases, the reaction required hospitalization, and 28 patients were taking other medications. Dechallenge was positive in 40 reactions (73%), rechallenge was positive in 7. Causality resulted as certain (1), probable (31, 56%), possible (18, 34%), unlikely (3) or unassessable (2). Similar distribution emerged from the WHO-Vigibase.ConclusionsThe potential safety signals of myopathies and liver injury raise the hypothesis that the safety profile of RYR is similar to that of statins. Continuous monitoring of dietary supplements should be promoted to finally characterize their risk profile, thus supporting regulatory bodies for appropriate actions.
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Project description:AimsCanagliflozin is a recently approved drug for use in the treatment of type 2 diabetes. The potential for canagliflozin to cause clinical drug-drug interactions (DDIs) was assessed.MethodsDDI potential of canagliflozin was investigated using in vitro test systems containing drug metabolizing enzymes or transporters. Basic predictive approaches were applied to determine potential interactions in vivo. A physiologically-based pharmacokinetic (PBPK) model was developed and clinical DDI simulations were performed to determine the likelihood of cytochrome P450 (CYP) inhibition by canagliflozin.ResultsCanagliflozin was primarily metabolized by uridine 5'-diphospho-glucuronosyltransferase 1A9 and 2B4 enzymes. Canagliflozin was a substrate of efflux transporters (P-glycoprotein, breast cancer resistance protein and multidrug resistance-associated protein-2) but was not a substrate of uptake transporters (organic anion transporter polypeptide isoforms OATP1B1, OATP1B3, organic anion transporters OAT1 and OAT3, and organic cationic transporters OCT1, and OCT2). In inhibition assays, canagliflozin was shown to be a weak in vitro inhibitor (IC50 ) of CYP3A4 (27 μmol l -1 , standard error [SE] 4.9), CYP2C9 (80 μmol l -1 , SE 8.1), CYP2B6 (16 μmol l-1 , SE 2.1), CYP2C8 (75 μmol l -1 , SE 6.4), P-glycoprotein (19.3 μmol l -1 , SE 7.2), and multidrug resistance-associated protein-2 (21.5 μmol l -1 , SE 3.1). Basic models recommended in DDI guidelines (US Food & Drug Administration and European Medicines Agency) predicted moderate to low likelihood of interaction for these CYPs and efflux transporters. PBPK DDI simulations of canagliflozin with CYP probe substrates (simvastatin, S-warfarin, bupropion, repaglinide) did not show relevant interaction in humans since mean areas under the concentration-time curve and maximum plasma concentration ratios for probe substrates with and without canagliflozin and its 95% CIs were within 0.80-1.25.ConclusionsIn vitro DDI followed by a predictive or PBPK approach was applied to determine DDI potential of canagliflozin. Overall, canagliflozin is neither a perpetrator nor a victim of clinically important interactions.
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Project description:Recently, new technologies have been combined to improve quality and sensorial diversity of wine. Several fining agents were developed to induce flocculation and sedimentation of particulate matter in wine, enhancing its clarification, and stabilization. The fining agents most commonly used are animal proteins, such as milk casein or egg albumin. However, its use is being related to food intolerance. To overcome this issue, alternative sources should be explored for use in industrial processes. In previous studies performed by our consortium, the potential of yeast protein extracts (YPE) in white wine clarification, stabilization, and curative processes was identified. Thus, the main objective of the present work is to select YPE with the potential to develop fining agents for red wine, without health risk to consumers. Therefore, five yeast strains were selected from a diversified collection of oenological yeasts, in order to produce protein extracts. Along with the fining trials, a vinification assay was performed to evaluate the maceration effect of the obtained YPE. The previously selected yeast strains were also screened for the production of the usual enzymatic activities found in commercial maceration preparations, namely polygalacturonase, cellulase, protease, and ß-glucosidase activities, in order to evaluate its potential effect on wine. Our results indicate that YPE, particularly BCVII 1, BCVII 2, and BCVII 5 were able to promote a significant brilliance increase, along with a turbidity reduction and final color improvement. In the vinification assay, BCVII 2 stands out with better results for color intensity and phenolic compounds content improvement. In what refers to enzymatic activities, BCVII 2 shows advantage over the other YPEs, due to its protease and β-glucosidase activity. We demonstrate that the selected YPEs, with emphasis on BCVII 2, may represent an efficient alternative to the commonly used fining products.
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Project description:Red yeast rice (RYR) can reduce cholesterol through its active component, lovastatin. This study was to investigate the pharmacokinetic properties of lovastatin in RYR products and potential RYR-drug interactions. Extracts of three registered RYR products (LipoCol Forte, Cholestin, and Xuezhikang) were more effective than pure lovastatin in inhibiting the activities of cytochrome P450 enzymes and P-glycoprotein. Among CYP450 enzymes, RYR showed the highest inhibition on CYP1A2 and CYP2C19, with comparable inhibitory potencies to the corresponding typical inhibitors. In healthy volunteers taking the RYR product LipoCol Forte, the pharmacokinetic properties of lovastatin and lovastatin acid were linear in the dose range of 1 to 4 capsules taken as a single dose and no significant accumulation was observed after multiple dosing. Concomitant use of one LipoCol Forte capsule with nifedipine did not change the pharmacokinetics of nifedipine. Yet, concomitant use of gemfibrozil with LipoCol Forte resulted in a significant increase in the plasma concentration of lovastatin acid. These findings suggest that the use of RYR products may not have effects on the pharmacokinetics of concomitant comedications despite their effects to inhibit the activities of CYP450 enzymes and P-gp, whereas gemfibrozil affects the pharmacokinetics of lovastatin acid when used concomitantly with RYR products.
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Project description:Serious concerns are expressed on the safe use of red yeast rice (RYR) supplements. The aim of the present study was to analyse cases received by Lareb on RYR-related adverse health events. These cases were analysed for the number of reports, number of adverse drug reactions (ADRs), causality, seriousness of the reaction, latency-period, age and sex of the patients, concomitant medication and type of reporter. A total of 94 individual reports were collected by Lareb, corresponding with 187 ADRs. The analysis showed most reported ADRs were labelled musculoskeletal and connective tissue disorders (n = 64), gastrointestinal disorders (n = 33) and general disorders and administration site conditions (n = 23). The use of RYR supplements should be considered as a significant safety concern. Exposure to monacolin K could lead to serious adverse effects. To fully assess the safety profile of RYR supplements, more research is necessary to compose a complete ADR profile of RYR supplements.
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Project description:Mildew resistance locus o (MLO) proteins are heptahelical integral membrane proteins of which some isoforms act as susceptibility factors for the powdery mildew pathogen. In many angiosperm plant species, loss-of-function mlo mutants confer durable broad-spectrum resistance against the fungal disease. Barley Mlo is known to interact via a cytosolic carboxyl-terminal domain with the intracellular calcium sensor calmodulin (CAM) in a calcium-dependent manner. Site-directed mutagenesis has revealed key amino acid residues in the barley Mlo calmodulin-binding domain (CAMBD) that, when mutated, affect the MLO-CAM association. We here tested the respective interaction between Arabidopsis thaliana MLO2 and CAM2 using seven different types of in vitro and in vivo protein-protein interaction assays. In each assay, we deployed a wild-type version of either the MLO2 carboxyl terminus (MLO2CT), harboring the CAMBD, or the MLO2 full-length protein and corresponding mutant variants in which two key residues within the CAMBD were substituted by non-functional amino acids. We focused in particular on the substitution of two hydrophobic amino acids (LW/RR mutant) and found in most protein-protein interaction experiments reduced binding of CAM2 to the corresponding MLO2/MLO2CT-LW/RR mutant variants in comparison with the respective wild-type versions. However, the Ura3-based yeast split-ubiquitin system and in planta bimolecular fluorescence complementation (BiFC) assays failed to indicate reduced CAM2 binding to the mutated CAMBD. Our data shed further light on the interaction of MLO and CAM proteins and provide a comprehensive comparative assessment of different types of protein-protein interaction assays with wild-type and mutant versions of an integral membrane protein.
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Project description:This study aimed to determine the effect and potential of red rice in conjunction with barley and rhododendron extracts to develop a new variant of beer. In this study red rice, barley, and rhododendron extracts were used in different combinations and the best combination was selected based on quality and sensory characteristics. The results showed that the developed beer was rich in antioxidant activity (47.68 ± 0.96) and contained a good amount of anthocyanin (35.12 ± 0.79), flavonoids (0.119 ± 0.002), and polyphenols (0.410 ± 0.002). The red rice has more dietary significance than that of polished or milled rice, further, the use of rhododendron provides a large number of secondary metabolites such as tannins, saponins, alkaloids, tannins, and flavonoids. Besides, the sensory profile of the developed beer was quite distinct in terms of aroma, taste, and color from other alternatives available in the market.
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