TY - JOUR A1 - Zhang, Nan A1 - Van Crombruggen, Koen A1 - Holtappels, Gabriele A1 - Lan, Feng A1 - Katotomichelakis, Michail A1 - Zhang, Luo A1 - Högger, Petra A1 - Bachert, Claus T1 - Suppression of Cytokine Release by Fluticasone Furoate vs. Mometasone Furoate in Human Nasal Tissue Ex-Vivo JF - PLOS ONE N2 - Background: Topical glucocorticosteroids are the first line therapy for airway inflammation. Modern compounds with higher efficacy have been developed, but head-to-head comparison studies are sparse. Objective: To compare the activity of two intranasal glucocorticoids, fluticasone furoate (FF) and mometasone furoate (MF) with respect to the inhibition of T helper (Th)1, Th2 and Th17 cytokine release in airway mucosa. Methods: We used an ex-vivo human nasal mucosal tissue model and employed pre-and post-Staphylococcus aureus enterotoxin B (SEB)-challenge incubations with various time intervals and drug concentrations to mimic typical clinical situations of preventive or therapeutic use. Results: At a fixed concentration of 10(-10) M, FF had significantly higher suppressive effects on interferon (IFN)-gamma,interleukin (IL)-2 and IL-17 release, but not IL-5 or tumor necrosis factor (TNF)-alpha, vs. MF. While the maximal suppressive activity was maintained when FF was added before or after tissue stimulation, the cytokine suppression capacity of MF appeared to be compromised when SEB-induced cell activation preceded the addition of the drug. In a pre-challenge incubation setting with removal of excess drug concentrations, MF approached inhibition of IL-5 and TNF-alpha after 6 and 24 hours while FF maximally blocked the release of these cytokines right after pre-incubation. Furthermore, FF suppressed a wider range of T helper cytokines compared to MF. Conclusion: The study demonstrates the potential of our human mucosal model and shows marked differences in the ability to suppress the release of various cytokines in pre-and post-challenge settings between FF and MF mimicking typical clinical situations of preventive or therapeutic use. KW - allergic rhinitis KW - human receptor kinetics KW - staphylococcus aureus KW - intranasal corticosteroids KW - cells KW - propionate KW - secretion KW - affinity KW - therapy KW - spray Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116779 VL - 9 IS - 4 ER - TY - JOUR A1 - Dirimanov, Stoyan A1 - Högger, Petra T1 - Screening of inhibitory effects of polyphenols on Akt-phosphorylation in endothelial cells and determination of structure-activity features JF - Biomolecules N2 - Polyphenols exert beneficial effects in type 2 diabetes mellitus (T2DM). However, their mechanism of action remains largely unknown. Endothelial Akt-kinase plays a key role in the pathogenesis of cardiovascular complications in T2DM and therefore the modulation of its activity is of interest. This work aimed to characterize effects of structurally different polyphenols on Akt-phosphorylation (pAkt) in endothelial cells (Ea.hy926) and to describe structure-activity features. A comprehensive screening via ELISA quantified the effects of 44 polyphenols (10 µM) on pAkt Ser473. The most pronounced inhibitors were luteolin (44 ± 18%), quercetin (36 ± 8%), urolithin A (35 ± 12%), apigenin, fisetin, and resveratrol; (p < 0.01). The results were confirmed by Western blotting and complemented with corresponding experiments in HUVEC cells. A strong positive and statistically significant correlation between the mean inhibitory effects of the tested polyphenols on both Akt-residues Ser473 and Thr308 (r = 0.9478, p = 0.0003) was determined by immunoblotting. Interestingly, the structural characteristics favoring pAkt inhibition partially differed from structural features enhancing the compounds’ antioxidant activity. The present study is the first to quantitatively compare the influence of polyphenols from nine different structural subclasses on pAkt in endothelial cells. These effects might be advantageous in certain T2DM-complications involving over-activation of the Akt-pathway. The suggested molecular mode of action of polyphenols involving Akt-inhibition contributes to understanding their effects on the cellular level. KW - Akt/PKB KW - endothelium KW - diabetes KW - polyphenols KW - in vitro KW - structure-activity relationships KW - screening Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197333 SN - 2218-273X VL - 9 IS - 6 ER - TY - JOUR A1 - Högger, Petra T1 - Nutrition-derived bioactive metabolites produced by gut microbiota and their potential impact on human health N2 - The functional role of human gut microbiota has attracted substantial interest and recent research has uncovered various aspects of the interplay between the complex communities of microorganisms colonizing the intestine and their hosts’ health. The present review focuses on nutrition-derived bioactive metabolites produced by gut microbiota with potential beneficial effects upon human health. Thereby, the emphasis is on newly generated bacterial metabolites that are not concomitantly present at higher amounts in dietary sources and that have been previously detected in human blood samples. Since a multitude of different substances is generated by gut microbes primarily those metabolites which exert a more pronounced activity than their immediate precursor compound are discussed here. Specifically, the in vitro and in vivo nutridynamics as well as the nutrikinetics of equol, enterolactone / enterodiol, urolithins, 8-prenylnaringenin, 3,4-dihydroxyphenylacetic acid and 5-(3’,4’-dihydroxyphenyl)-g-valerolactone, the short-chain fatty acids butyrate, propionate and acetate, and indole-3-propionic acid are reviewed. Though the metabolites’ mechanism of action and the influence of health conditions on metabolite production are not always fully understood yet, there are many reasons to direct the attention to “gut health”. It could offer new options for preventing or treating a variety of disease states and nutrition-derived microbial products might inspire future drug development. KW - Kohlenhydrate KW - Tryptophan KW - gut microbiota; bioactivation; polyphenols; complex carbohydrates; tryptophan Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77349 ER - TY - JOUR A1 - Schreier, Peter A1 - Binns, Colin A1 - Högger, Petra A1 - Wu, Dayong T1 - It began with citrus N2 - First Editorial of Open Access Journal "Nutrition and Medicine (NUME)" published by Würzburg University Press: http://nume.de KW - Ernährung KW - Medizin KW - Citrus KW - Geschichte KW - nutrition KW - medicine KW - citrus KW - history Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-74918 ER - TY - JOUR A1 - Högger, Petra A1 - Kurlbaum, Max A1 - Mülek, Melanie T1 - Facilitated Uptake of a Bioactive Metabolite of Maritime Pine Bark Extract (Pycnogenol) into Human Erythrocytes JF - PLoS ONE N2 - Many plant secondary metabolites exhibit some degree of biological activity in humans. It is a common observation that individual plant-derived compounds in vivo are present in the nanomolar concentration range at which they usually fail to display measurable activity in vitro. While it is debatable that compounds detected in plasma are not the key effectors of bioactivity, an alternative hypothesis may take into consideration that measurable concentrations also reside in compartments other than plasma. We analysed the binding of constituents and the metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone (M1), that had been previously detected in plasma samples of human consumers of pine bark extract Pycnogenol, to human erythrocytes. We found that caffeic acid, taxifolin, and ferulic acid passively bind to red blood cells, but only the bioactive metabolite M1 revealed pronounced accumulation. The partitioning of M1 into erythrocytes was significantly diminished at higher concentrations of M1 and in the presence of glucose, suggesting a facilitated transport of M1 via GLUT-1 transporter. This concept was further supported by structural similarities between the natural substrate α-D-glucose and the S-isomer of M1. After cellular uptake, M1 underwent further metabolism by conjugation with glutathione. We present strong indication for a transporter-mediated accumulation of a flavonoid metabolite in human erythrocytes and subsequent formation of a novel glutathione adduct. The physiologic role of the adduct remains to be elucidated. KW - blood plasma KW - cell metabolism KW - drug metabolism KW - glucose KW - glucos metabolism KW - glutathione KW - plasma proteins KW - red blood cells Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96656 ER - TY - JOUR A1 - Mülek, Melanie A1 - Seefried, Lothar A1 - Genest, Franca A1 - Högger, Petra T1 - Distribution of constituents and metabolites of maritime pine bark extract (Pycnogenol\(^{®}\)) into serum, blood cells, and synovial fluid of patients with severe osteoarthritis: a randomized controlled trial JF - Nutrients N2 - The present randomized controlled study aimed to investigate the in vivo distribution of constituents or metabolites of the standardized maritime pine bark extract Pycnogenol\(^{®}\). Thirty-three patients with severe osteoarthritis scheduled for a knee arthroplasty were randomized to receive either 200 mg per day Pycnogenol\(^{®}\) (P+) or no treatment (Co) over three weeks before surgery. Serum, blood cells, and synovial fluid samples were analyzed using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization (LC-ESI/MS/MS). Considerable interindividual differences were observed indicating pronounced variability of the polyphenol pharmacokinetics. Notably, the highest polyphenol concentrations were not detected in serum. Catechin and taxifolin primarily resided within the blood cells while the microbial catechin metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone, ferulic, and caffeic acid were mainly present in synovial fluid samples. Taxifolin was detected in serum and synovial fluid exclusively in the P+ group. Likewise, no ferulic acid was found in serum samples of the Co group. Calculating ratios of analyte distribution in individual patients revealed a simultaneous presence of some polyphenols in serum, blood cells, and/or synovial fluid only in the P+ group. This is the first evidence that polyphenols distribute into the synovial fluid of patients with osteoarthritis which supports rationalizing the results of clinical efficacy studies. KW - osteoarthritis KW - randomized controlled study KW - LC-ESI/MS/MS KW - human KW - pine bark extract KW - polyphenols Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159862 VL - 9 IS - 5 ER - TY - JOUR A1 - Volpp, Linda A1 - Ferianec, Vladimír A1 - Ježovičová, Miriam A1 - Ďuračková, Zdeňka A1 - Scherf-Clavel, Oliver A1 - Högger, Petra T1 - Constituents and Metabolites of a French Oak Wood Extract (Robuvit®) in Serum and Blood Cell Samples of Women Undergoing Hysterectomy JF - Frontiers in Pharmacology N2 - Ellagitannins are signature constituents of oak wood and their consumption has been associated with various health benefits. In vivo, they undergo metabolic degradation including gut microbial metabolism yielding urolithins. Only limited data is available about compounds being present in blood after intake of an extract from French oak wood, Robuvit®. In the course of a randomized, double-blind, controlled clinical investigation, 66 patients undergoing hysterectomy received placebo or 300 mg Robuvit® per day before and over 8 weeks after surgery. Serum and blood cell samples were analyzed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The number of urolithin producers and the urolithin levels increased after intake of Robuvit®. In serum samples, the median concentration of urolithin A was 14.0 ng/ml [interquartile range (IQR) 57.4] after 8 weeks. Urolithin B was determined at 22.3 ng/ml (IQR 12.6), urolithin C at 2.66 ng/ml (IQR 2.08). In blood cells, lower concentrations and only urolithins A and B were detected. A statistically significant association of lower post-surgical pain scores with metabotype A was detected (p < 0.05). To conclude, supplementation with French oak wood extract raised urolithin generation in patients and suggested health advantages for urolithin-producers. KW - polyphenols KW - urolithins KW - oak wood KW - post-surgery recovery KW - human KW - liquid chromatography electrospray ionization tandem mass spectrometry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200105 SN - 1663-9812 VL - 11 IS - 74 ER - TY - JOUR A1 - Jessberger, Steffen A1 - Högger, Petra A1 - Genest, Franca A1 - Salter, Donald M. A1 - Seefried, Lothar T1 - Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study JF - BMC Complementary and Alternative Medicine N2 - Background: The standardized maritime pine bark extract (Pycnogenol\(^{®}\)) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol\(^{®}\) and its in vivo mechanism of action in OA patients. Methods: Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol\(^{®}\) twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. Results: The oral intake of Pycnogenol\(^{®}\) downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. Conclusions: This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol\(^{®}\) on symptom scores of patients suffering from OA. KW - maritime pine bark extract KW - qPCR KW - ADAMTS KW - cartilage KW - clinical study KW - osteoarthritis KW - Pycnogenol KW - serum KW - synovial fluid Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159532 VL - 17 IS - 537 ER - TY - CHAP A1 - Högger, Petra A1 - Xiao, Jianbo T1 - Abstracts of the International Symposium on Phytochemicals in Medicine and Food N2 - The International Symposium on Phytochemicals in Medicine and Food (ISPMF2015), organized by the Phytochemical Society of Europe (PSE) and the Phytochemical Society of Asia (PSA), was held June 26-29, 2015, in Shanghai of China. This was the first time that a PSE meeting has been held in Asia and a PSE-PSA joint symposium provided an opportunity for communication between scientists from Europe and Asia and other continents. ISPMF2015 has been jointly sponsored by Fujian Agriculture and Forestry University, Guizhou Medical University, Shanghai Normal University, Yancheng Institute of Technology, Beijing Normal University, and Fudan University. More than 270 scientists from 48 countries attended this meeting and presented their research and opinions on phytochemistry, phytomedicine and phytoneering. The international organizing committee and scientific advisory board of ISPMF 2015 comprised of outstanding scientists from around the globe. Dr. Jianbo Xiao was the chairman of the International Organizing Committee of ISPMF2015 and moderated the open address on June 26. The organizing committee of ISPMF2015 assembled an exciting and diverse program, featuring 16 sessions including 12 plenary lectures, 20 invited talks, 55 short oral presentations, and more than 130 posters, which were dedicated to creating a podium for exchanging the latest research results in the phytochemicals for food and human health. KW - phytoneering KW - phytomedicine KW - nutrition KW - food KW - medicine KW - phytochemistry KW - ISPMF Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121585 ER -