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Dietary (Poly)Phenols and Health

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Phytochemicals and Human Health".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 129528

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Guest Editor
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovskeho 1203/8, 500 05 Hradec Králové, Czech Republic
Interests: flavonoid; phenolic; coumarin; cardiovascular; trace metals; platelet
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Previously, the positive effects of (poly)phenolic compounds on human health were explained by direct scavenging effect of the parent compounds toward reactive oxygen and nitrogen species. However, recently, a number of publications have documented specific effects of dietary (poly)phenolics mediated by their metabolites. This Special Issue aims to present novel findings documenting the relevant effects (positive but potentially also negative) of dietary (poly)phenolic compounds taking their pharmacokinetics in the consideration. Relevant effects refer to the activities which can have a potential clinical impact on human diseases and/or health. Emphasis will be given to miscellaneous metabolites, including conjugates formed by human enzymes and small phenolic compounds formed by the gastrointestinal microflora.

Original articles, review papers, and short communications with significant novelty are welcome. Papers reporting the effects of plant extracts are also acceptable but only on the condition that they include the specification of (at least major) contained substances and pharmacokinetic data or are based on reliable previous publications.

Prof. Dr. Přemysl Mladěnka
Guest Editor

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Keywords

  • polyphenol
  • natural
  • metabolite
  • disorder
  • flavonoid
  • coumarin
  • lignan
  • phenolic acid

Published Papers (20 papers)

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Editorial

Jump to: Research, Review

4 pages, 451 KiB  
Editorial
Special Issue “Dietary (Poly)Phenols and Health”
by Přemysl Mladěnka
Nutrients 2022, 14(7), 1402; https://doi.org/10.3390/nu14071402 - 28 Mar 2022
Cited by 2 | Viewed by 1502
Abstract
Interest in understanding the mechanisms of the positive effects of dietary phenolic and polyphenolic compounds on human health has markedly increased in recent years [...] Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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Research

Jump to: Editorial, Review

22 pages, 9821 KiB  
Article
Silymarin Dehydroflavonolignans Chelate Zinc and Partially Inhibit Alcohol Dehydrogenase
by Václav Tvrdý, Marcel Hrubša, Eduard Jirkovský, David Biedermann, Michal Kutý, Kateřina Valentová, Vladimír Křen and Přemysl Mladěnka
Nutrients 2021, 13(12), 4238; https://doi.org/10.3390/nu13124238 - 25 Nov 2021
Cited by 10 | Viewed by 2645
Abstract
Silymarin is known for its hepatoprotective effects. Although there is solid evidence for its protective effects against Amanita phalloides intoxication, only inconclusive data are available for alcoholic liver damage. Since silymarin flavonolignans have metal-chelating activity, we hypothesized that silymarin may influence alcoholic liver [...] Read more.
Silymarin is known for its hepatoprotective effects. Although there is solid evidence for its protective effects against Amanita phalloides intoxication, only inconclusive data are available for alcoholic liver damage. Since silymarin flavonolignans have metal-chelating activity, we hypothesized that silymarin may influence alcoholic liver damage by inhibiting zinc-containing alcohol dehydrogenase (ADH). Therefore, we tested the zinc-chelating activity of pure silymarin flavonolignans and their effect on yeast and equine ADH. The most active compounds were also tested on bovine glutamate dehydrogenase, an enzyme blocked by zinc ions. Of the six flavonolignans tested, only 2,3-dehydroderivatives (2,3-dehydrosilybin and 2,3-dehydrosilychristin) significantly chelated zinc ions. Their effect on yeast ADH was modest but stronger than that of the clinically used ADH inhibitor fomepizole. In contrast, fomepizole strongly blocked mammalian (equine) ADH. 2,3-Dehydrosilybin at low micromolar concentrations also partially inhibited this enzyme. These results were confirmed by in silico docking of active dehydroflavonolignans with equine ADH. Glutamate dehydrogenase activity was decreased by zinc ions in a concentration-dependent manner, and this inhibition was abolished by a standard zinc chelating agent. In contrast, 2,3-dehydroflavonolignans blocked the enzyme both in the absence and presence of zinc ions. Therefore, 2,3-dehydrosilybin might have a biologically relevant inhibitory effect on ADH and glutamate dehydrogenase. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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12 pages, 2146 KiB  
Article
Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis
by Lia Tsiklauri, Karol Švík, Martin Chrastina, Silvester Poništ, František Dráfi, Lukáš Slovák, Mery Alania, Ether Kemertelidze and Katarina Bauerova
Nutrients 2021, 13(4), 1268; https://doi.org/10.3390/nu13041268 - 13 Apr 2021
Cited by 14 | Viewed by 2915
Abstract
Anti-inflammatory potential of orally administrated bioflavonoid-robinin, active sub-stance of original drug Flaroninum™ (FL), was investigated in the combination with methotrexate (MTX) and in monotherapy in rats suffering from adjuvant-induced arthritis (AA). Robinin (kaempferol-3-O-robinoside-7-O-rhamnoside) was isolated from the aerial parts [...] Read more.
Anti-inflammatory potential of orally administrated bioflavonoid-robinin, active sub-stance of original drug Flaroninum™ (FL), was investigated in the combination with methotrexate (MTX) and in monotherapy in rats suffering from adjuvant-induced arthritis (AA). Robinin (kaempferol-3-O-robinoside-7-O-rhamnoside) was isolated from the aerial parts of Astragalus falcatus Lam. The monotherapy with robinin was not efficient in alleviating symptoms of AA. The combination of MTX with robinin was similarly active as MTX alone in reducing the hind paw volume and change of body weight during the whole experiment. The combination, however, reduced plasma levels of Interleukin-17Aand activity of gamma-glutamyl transferase in joint more efficiently then MTX alone. Our results demonstrate that the novel combination of robinin and MTX mildly improved the reduction of inflammation in experimental arthritis. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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16 pages, 965 KiB  
Article
The Effects of a Functional Food Breakfast on Gluco-Regulation, Cognitive Performance, Mood, and Satiety in Adults
by Sarah J. Kennedy, Lisa Ryan and Miriam E. Clegg
Nutrients 2020, 12(10), 2974; https://doi.org/10.3390/nu12102974 - 29 Sep 2020
Cited by 5 | Viewed by 3999
Abstract
A whole diet which combines multiple functional foods benefits metabolic risk factors and cognition, but evidence supporting meal to meal benefits, which individuals may find easier to implement, is limited. This study developed a functional food breakfast (FB), using polyphenol-rich ingredients selected for [...] Read more.
A whole diet which combines multiple functional foods benefits metabolic risk factors and cognition, but evidence supporting meal to meal benefits, which individuals may find easier to implement, is limited. This study developed a functional food breakfast (FB), using polyphenol-rich ingredients selected for their gluco-regulating and cognitive-enhancing properties, and compared it to a control breakfast (CB). For study 1, total polyphenols were determined using the Folin–Ciocalteu method, and sugar release by in vitro digestion, in frozen and fresh samples. In study 2, healthy adults (n = 16) consumed an FB, CB and ready-to-eat breakfast cereal (RTEC) in a randomised crossover design. Glucose (GR) and insulin response (IR), satiety, mood and memory were measured over 180 min. The FB was a rich source of polyphenols (230 mg) compared to the CB (147 mg) (p < 0.05), and using frozen muffins did not compromise the polyphenol content or sugar release. Peak GR was highest after the RTEC (p < 0.05), and the insulin area under the curve (AUC) was lowest in the FB at 60, 120, 180 min and peak (p < 0.05). There were no effects on GR AUC, mood, satiety or memory. Reductions in GR peak and IR following consumption of the FB support the inclusion of functional ingredients at breakfast. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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35 pages, 4853 KiB  
Article
The Impact of a Polyphenol-Rich Extract from the Berries of Aronia melanocarpa L. on Collagen Metabolism in the Liver: A Study in an In Vivo Model of Human Environmental Exposure to Cadmium
by Magdalena Kozłowska, Małgorzata M. Brzóska, Joanna Rogalska and Anna Galicka
Nutrients 2020, 12(9), 2766; https://doi.org/10.3390/nu12092766 - 10 Sep 2020
Cited by 8 | Viewed by 3005
Abstract
This study examined whether a polyphenol-rich extract from the berries of Aronia melanocarpa L. (AE; chokeberries) may protect from the impact of cadmium (Cd) on the metabolism of collagen in the liver. The study was conducted in an experimental model (rats that were [...] Read more.
This study examined whether a polyphenol-rich extract from the berries of Aronia melanocarpa L. (AE; chokeberries) may protect from the impact of cadmium (Cd) on the metabolism of collagen in the liver. The study was conducted in an experimental model (rats that were fed a diet containing 1 or 5 mg Cd/kg for 3–24 months) of human exposure to this xenobiotic during a lifetime. The concentration of total collagen and the expression of collagen types I and III at the mRNA and protein levels, as well as the concentrations of matrix metalloproteinases (MMP-1 and MMP-2) and their tissue inhibitors (TIMP-1 and TIMP-2), were assayed. The administration of Cd and/or AE had only a slight and temporary impact on the concentration of total collagen in the liver. The supplementation with AE significantly prevented Cd-mediated changes in the expression of collagen types I and III at the mRNA and protein levels and their ratio (collagen III/collagen I), as well as a rise in the concentrations of MMPs and TIMPs in this organ. The results allow the conclusion that the intake of chokeberry products in the case of Cd intoxication may be effective in prevention from this xenobiotic-induced disturbance in collagen homeostasis in the liver. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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16 pages, 3111 KiB  
Article
Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters
by Violetta Mohos, Eszter Fliszár-Nyúl, Orsolya Ungvári, Katalin Kuffa, Paul W. Needs, Paul A. Kroon, Ágnes Telbisz, Csilla Özvegy-Laczka and Miklós Poór
Nutrients 2020, 12(8), 2306; https://doi.org/10.3390/nu12082306 - 31 Jul 2020
Cited by 44 | Viewed by 5310
Abstract
Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact [...] Read more.
Quercetin is a flavonoid, its glycosides and aglycone are found in significant amounts in several plants and dietary supplements. Because of the high presystemic biotransformation of quercetin, mainly its conjugates appear in circulation. As has been reported in previous studies, quercetin can interact with several proteins of pharmacokinetic importance. However, the interactions of its metabolites with biotransformation enzymes and drug transporters have barely been examined. In this study, the inhibitory effects of quercetin and its most relevant methyl, sulfate, and glucuronide metabolites were tested on cytochrome P450 (CYP) (2C19, 3A4, and 2D6) enzymes as well as on organic anion-transporting polypeptides (OATPs) (OATP1A2, OATP1B1, OATP1B3, and OATP2B1) and ATP (adenosine triphosphate) Binding Cassette (ABC) (BCRP and MRP2) transporters. Quercetin and its metabolites (quercetin-3′-sulfate, quercetin-3-glucuronide, isorhamnetin, and isorhamnetin-3-glucuronide) showed weak inhibitory effects on CYP2C19 and 3A4, while they did not affect CYP2D6 activity. Some of the flavonoids caused weak inhibition of OATP1A2 and MRP2. However, most of the compounds tested proved to be strong inhibitors of OATP1B1, OATP1B3, OATP2B1, and BCRP. Our data demonstrate that not only quercetin but some of its conjugates, can also interact with CYP enzymes and drug transporters. Therefore, high intake of quercetin may interfere with the pharmacokinetics of drugs. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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16 pages, 1217 KiB  
Article
A Randomized, Crossover Study of the Acute Cognitive and Cerebral Blood Flow Effects of Phenolic, Nitrate and Botanical Beverages in Young, Healthy Humans
by Philippa A. Jackson, Emma L. Wightman, Rachel Veasey, Joanne Forster, Julie Khan, Caroline Saunders, Siobhan Mitchell, Crystal F. Haskell-Ramsay and David O. Kennedy
Nutrients 2020, 12(8), 2254; https://doi.org/10.3390/nu12082254 - 28 Jul 2020
Cited by 20 | Viewed by 4756
Abstract
Background: In whole foods, polyphenols exist alongside a wide array of other potentially bioactive phytochemicals. Yet, investigations of the effects of combinations of polyphenols with other phytochemicals are limited. Objective: The current study investigated the effects of combining extracts of beetroot, ginseng and [...] Read more.
Background: In whole foods, polyphenols exist alongside a wide array of other potentially bioactive phytochemicals. Yet, investigations of the effects of combinations of polyphenols with other phytochemicals are limited. Objective: The current study investigated the effects of combining extracts of beetroot, ginseng and sage with phenolic-rich apple, blueberry and coffee berry extracts. Design: This randomized, double-blind, placebo-controlled crossover design investigated three active beverages in 32 healthy adults aged 18–49 years. Each investigational beverage comprised extracts of beetroot, ginseng and sage. Each also contained a phenolic-rich extract derived from apple (containing 234 mg flavanols), blueberry (300 mg anthocyanins) or coffee berry (440 mg chlorogenic acid). Cognition, mood and CBF parameters were assessed at baseline and then again at 60, 180 and 360 min post-drink. Results: Robust effects on mood and CBF were seen for the apple and coffee berry beverages, with increased subjective energetic arousal and hemodynamic responses being observed. Fewer effects were seen with the blueberry extract beverage. Conclusions: Either the combination of beetroot, ginseng and sage was enhanced by the synergistic addition of the apple and coffee berry extract (and to a lesser extent the blueberry extract) or the former two phenolic-rich extracts were capable of evincing the robust mood and CBF effects alone. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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14 pages, 2533 KiB  
Article
The Modulation of Phase II Drug-Metabolizing Enzymes in Proliferating and Differentiated CaCo-2 Cells by Hop-Derived Prenylflavonoids
by Kateřina Lněničková, Michaela Šadibolová, Petra Matoušková, Barbora Szotáková, Lenka Skálová and Iva Boušová
Nutrients 2020, 12(7), 2138; https://doi.org/10.3390/nu12072138 - 18 Jul 2020
Cited by 15 | Viewed by 3490
Abstract
Prenylflavonoids in the human organism exhibit various health-beneficial activities, although they may interfere with drugs via the modulation of the expression and/or activity of drug-metabolizing enzymes. As intestinal cells are exposed to the highest concentrations of prenylflavonoids, we decided to study the cytotoxicity [...] Read more.
Prenylflavonoids in the human organism exhibit various health-beneficial activities, although they may interfere with drugs via the modulation of the expression and/or activity of drug-metabolizing enzymes. As intestinal cells are exposed to the highest concentrations of prenylflavonoids, we decided to study the cytotoxicity and modulatory effects of the four main hop-derived prenylflavonoids on the activities and mRNA expression of the main drug-conjugating enzymes in human CaCo-2 cells. Proliferating CaCo-2 cells were used for these purposes as a model of colorectal cancer cells, and differentiated CaCo-2 cells were used as an enterocyte-like model. All the tested prenylflavonoids inhibited the CaCo-2 cells proliferation, with xanthohumol proving the most effective (IC50 8.5 µM). The prenylflavonoids modulated the activities and expressions of the studied enzymes to a greater extent in the differentiated, as opposed to the proliferating, CaCo-2 cells. In the differentiated cells, all the prenylflavonoids caused a marked increase in glutathione S-transferase and catechol-O-methyltransferase activities, while the activity of sulfotransferase was significantly inhibited. Moreover, the prenylflavonoids upregulated the mRNA expression of uridine diphosphate (UDP)-glucuronosyl transferase 1A6 and downregulated that of glutathione S-transferase 1A1/2. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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11 pages, 1909 KiB  
Article
Characteristic Analysis of Trigonelline Contained in Raphanus sativus Cv. Sakurajima Daikon and Results from the First Trial Examining Its Vasodilator Properties in Humans
by Maho Sasaki, Yuri Nonoshita, Takashi Kajiya, Nobuhiko Atsuchi, Megumi Kido, Djong-Chi Chu, Lekh Raj Juneja, Yuji Minami and Katsuko Kajiya
Nutrients 2020, 12(6), 1872; https://doi.org/10.3390/nu12061872 - 23 Jun 2020
Cited by 9 | Viewed by 4552
Abstract
Vascular disease poses a major public health problem worldwide. Trigonelline isolated from Raphanus sativus cv. Sakurajima Daikon (Sakurajima radish) induces nitric oxide production from vascular endothelial cells and enhances vascular function. Here, we investigated the characteristics of trigonelline and its effects on endothelial [...] Read more.
Vascular disease poses a major public health problem worldwide. Trigonelline isolated from Raphanus sativus cv. Sakurajima Daikon (Sakurajima radish) induces nitric oxide production from vascular endothelial cells and enhances vascular function. Here, we investigated the characteristics of trigonelline and its effects on endothelial function after consumption of Sakurajima radish by humans. Our results show that Sakurajima radish contains approximately 60 times more trigonelline than other radishes and squashes. Additionally, no significant differences were observed between varieties of Sakurajima radish, suggesting that any type of Sakurajima radish can be ingested for trigonelline supplementation. The effects of cooking and processing Sakurajima radish were also evaluated, as were the effects of freezing, and changes in osmotic pressure and pH. A first-in-human trial using Sakurajima radish showed that ingestion of 170 g/day of Sakurajima radish for ten days increased blood trigonelline concentrations and significantly improved flow-mediated dilation, which is a measure of vascular endothelial function. Overall, our findings suggest that the trigonelline contained in Sakurajima radish may contribute to improved human vascular endothelial function. Hence, Sakurajima radish may enhance vascular endothelial function as a functional food. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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12 pages, 982 KiB  
Article
Consumption of Stilbenes and Flavonoids is Linked to Reduced Risk of Obesity Independently of Fiber Intake
by Olatz Mompeo, Tim D. Spector, Marisa Matey Hernandez, Caroline Le Roy, Geoffrey Istas, Melanie Le Sayec, Massimo Mangino, Amy Jennings, Ana Rodriguez-Mateos, Ana M. Valdes and Cristina Menni
Nutrients 2020, 12(6), 1871; https://doi.org/10.3390/nu12061871 - 23 Jun 2020
Cited by 19 | Viewed by 6335
Abstract
Background: Polyphenol consumption is implicated in gut microbiome composition and improved metabolic outcomes, but it is unclear whether the effect is independent of dietary fiber. Methods: We investigated the links between (poly)phenol intake, gut microbiome composition (16s RNA) and obesity independently of fiber [...] Read more.
Background: Polyphenol consumption is implicated in gut microbiome composition and improved metabolic outcomes, but it is unclear whether the effect is independent of dietary fiber. Methods: We investigated the links between (poly)phenol intake, gut microbiome composition (16s RNA) and obesity independently of fiber intake in UK women (n = 1810) and in a small group of UK men (n = 64). Results: (Poly)phenol intakes correlated with microbiome alpha diversity (Shannon Index) after adjusting for confounders and fiber intake. Moreover, flavonoid intake was significantly correlated with the abundance of Veillonella, (a genus known to improve physical performance), and stilbene intake with that of butyrate-producing bacteria (Lachnospira and Faecalibacterium). Stilbene and flavonoid intake also correlated with lower odds of prevalent obesity (Stilbenes: Odds Ratio (95% Confidence Interval) (OR(95%CI)) = 0.80 (0.73, 0.87), p = 4.90 × 10−7; Flavonoids: OR(95%CI) = 0.77 (0.65, 0.91), p = 0.002). Formal mediation analyses revealed that gut microbiome mediates ~11% of the total effect of flavonoid and stilbene intake on prevalent obesity. Conclusions: Our findings highlight the importance of (poly)phenol consumption for optimal human health. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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14 pages, 3174 KiB  
Article
Postprandial Glycemia, Insulinemia, and Antioxidant Status in Healthy Subjects after Ingestion of Bread made from Anthocyanin-Rich Riceberry Rice
by Charoonsri Chusak, Porntip Pasukamonset, Praew Chantarasinlapin and Sirichai Adisakwattana
Nutrients 2020, 12(3), 782; https://doi.org/10.3390/nu12030782 - 16 Mar 2020
Cited by 25 | Viewed by 5198
Abstract
Riceberry rice, a gluten-free grain, contains many nutrient components, including carbohydrates, proteins, certain fatty acids, and micronutrients, as well as bioactive non-nutrient compounds, such as polyphenolic compounds. This study aimed to evaluate the effect of bread made from anthocyanin-rich Riceberry rice on the [...] Read more.
Riceberry rice, a gluten-free grain, contains many nutrient components, including carbohydrates, proteins, certain fatty acids, and micronutrients, as well as bioactive non-nutrient compounds, such as polyphenolic compounds. This study aimed to evaluate the effect of bread made from anthocyanin-rich Riceberry rice on the postprandial glycemic response, glucagon-like peptide-1 (GLP-1), antioxidant status, and subjective ratings of appetite. In the crossover design, 16 healthy participants (six men and 10 women) completed four sessions involving blood collection in the fasting state and at 30, 60, 90, 120, 150, and 180 min after food consumption (50 g of available carbohydrate) in a randomized order: 1) glucose solution, 2) wheat bread (WB), 3) Riceberry rice bread (RRB), and 4) Hom Mali bread (HMB). Consumption of RRB resulted in significantly lower postprandial plasma glucose concentration at 30 and 60 min when compared to HMB. No difference in postprandial glucose concentration between RRB and WB was observed. In addition, postprandial plasma insulin showed a significant decrease in the group which received RRB at 15 and 60 min, as compared to HMB. In comparison with 50 g of glucose, as a reference, the glycemic index (GI) of RRB, WB, and HMB was 69.3 ± 4.4, 77.8 ± 4.6, and 130.6 ± 7.9, respectively. Interestingly, the ferric-reducing ability of plasma (FRAP) level was shown to significantly increase after consumption of RRB. In the meantime, a significant decrease in the postprandial FRAP level was also observed following an intake of WB and HMB. All breads caused increases in the postprandial plasma protein thiol group and had similar effects on hunger, fullness, desire to eat, and satiety ratings. However, consumption of RBB, WB, and HMB did not change plasma GLP-1 and malondialdehyde (MDA) levels when compared to the baseline. The findings suggest that anthocyanin-rich Riceberry rice can be a natural ingredient for gluten-free bread which reduced glycemic response together with improvement of antioxidant status in healthy subjects. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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6 pages, 1135 KiB  
Communication
A Mixture of Phenolic Metabolites of Quercetin Can Decrease Elevated Blood Pressure of Spontaneously Hypertensive Rats Even in Low Doses
by Iveta Najmanová, Jana Pourová and Přemysl Mladěnka
Nutrients 2020, 12(1), 213; https://doi.org/10.3390/nu12010213 - 14 Jan 2020
Cited by 18 | Viewed by 2907
Abstract
Quercetin is proven to decrease arterial blood pressure when given orally. Its bioavailability is, however, low and, therefore, its metabolites could rather be responsible for this effect. In particular, the colonic metabolites of quercetin, 3,4-dihydroxyphenylacetic acid (DHPA), 4-methylcatechol (4MC), and 3-(3-hydroxyphenyl)propionic acid (3HPPA), [...] Read more.
Quercetin is proven to decrease arterial blood pressure when given orally. Its bioavailability is, however, low and, therefore, its metabolites could rather be responsible for this effect. In particular, the colonic metabolites of quercetin, 3,4-dihydroxyphenylacetic acid (DHPA), 4-methylcatechol (4MC), and 3-(3-hydroxyphenyl)propionic acid (3HPPA), have been previously shown to decrease the blood pressure in spontaneously hypertensive rats (SHR). Interestingly, the mechanisms of action of these three metabolites are different. The aim of this study is hence to investigate if these metabolites can potentiate each other and thus decrease blood pressure in reduced doses. Three double-combinations of previously mentioned metabolites were administered to SHR as infusions to mimic a real biological situation. All combinations significantly decreased the blood pressure in SHR but there were important differences. The effect of DHPA and 4MC was mild and very short. A combination of DHPA with 3HPPA caused more pronounced effects, which were also rather short-lived. The last combination of 3HPPA and 4MC caused a long-lasting effect. In conclusion, certain combinations of quercetin metabolites have a more pronounced antihypertensive effect than single metabolites. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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Review

Jump to: Editorial, Research

40 pages, 1154 KiB  
Review
From Preclinical Stroke Models to Humans: Polyphenols in the Prevention and Treatment of Stroke
by Edoardo Parrella, Cristina Gussago, Vanessa Porrini, Marina Benarese and Marina Pizzi
Nutrients 2021, 13(1), 85; https://doi.org/10.3390/nu13010085 - 29 Dec 2020
Cited by 25 | Viewed by 6053
Abstract
Polyphenols are an important family of molecules of vegetal origin present in many medicinal and edible plants, which represent important alimentary sources in the human diet. Polyphenols are known for their beneficial health effects and have been investigated for their potential protective role [...] Read more.
Polyphenols are an important family of molecules of vegetal origin present in many medicinal and edible plants, which represent important alimentary sources in the human diet. Polyphenols are known for their beneficial health effects and have been investigated for their potential protective role against various pathologies, including cancer, brain dysfunctions, cardiovascular diseases and stroke. The prevention of stroke promoted by polyphenols relies mainly on their effect on cardio- and cerebrovascular systems. However, a growing body of evidence from preclinical models of stroke points out a neuroprotective role of these molecules. Notably, in many preclinical studies, the polyphenolic compounds were effective also when administered after the stroke onset, suggesting their possible use in promoting recovery of patients suffering from stroke. Here, we review the effects of the major polyphenols in cellular and in vivo models of both ischemic and hemorrhagic stroke in immature and adult brains. The results from human studies are also reported. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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23 pages, 2956 KiB  
Review
Moderators of the Impact of (Poly)Phenols Interventions on Psychomotor Functions and BDNF: Insights from Subgroup Analysis and Meta-Regression
by Achraf Ammar, Khaled Trabelsi, Omar Boukhris, Bassem Bouaziz, Patrick Müller, Jordan M. Glenn, Karim Chamari, Notger Müller, Hamdi Chtourou, Tarak Driss and Anita Hökelmann
Nutrients 2020, 12(9), 2872; https://doi.org/10.3390/nu12092872 - 19 Sep 2020
Cited by 7 | Viewed by 3814
Abstract
Background: Recent anti-aging interventions have shown contradictory impacts of (poly)phenols regarding the prevention of cognitive decline and maintenance of brain function. These discrepancies have been linked to between-study differences in supplementation protocols. This subgroup analysis and meta-regression aimed to (i) examine differential effects [...] Read more.
Background: Recent anti-aging interventions have shown contradictory impacts of (poly)phenols regarding the prevention of cognitive decline and maintenance of brain function. These discrepancies have been linked to between-study differences in supplementation protocols. This subgroup analysis and meta-regression aimed to (i) examine differential effects of moderator variables related to participant characteristics and supplementation protocols and (ii) identify practical recommendations to design effective (poly)phenol supplementation protocols for future anti-aging interventions. Methods: Multiple electronic databases (Web of Science; PubMed) searched for relevant intervention published from inception to July 2019. Using the PICOS criteria, a total of 4303 records were screened. Only high-quality studies (n = 15) were included in the final analyses. Random-effects meta-analysis was used, and we calculated standard differences in means (SDM), effect size (ES), and 95% confidence intervals (CI) for two sufficiently comparable items (i.e., psychomotor function and brain-derived neurotrophic factor (BDNF)). When significant heterogeneity was computed (I2 > 50%), a subgroup and meta-regression analysis were performed to examine the moderation effects of participant characteristics and supplementation protocols. Results: The reviewed studies support the beneficial effect of (poly)phenols-rich supplementation on psychomotor functions (ES = −0.677, p = 0.001) and brain plasticity (ES = 1.168, p = 0.028). Subgroup analysis revealed higher beneficial impacts of (poly)phenols (i) in younger populations compared to older (SDM = −0.89 vs. −0.47 for psychomotor performance, and 2.41 vs. 0.07 for BDNF, respectively), (ii) following an acute compared to chronic supplementation (SDM = −1.02 vs. −0.43 for psychomotor performance), and (iii) using a phenolic compound with medium compared to low bioavailability rates (SDM = −0.76 vs. −0.68 for psychomotor performance and 3.57 vs. 0.07 for DBNF, respectively). Meta-regressions revealed greater improvement in BDNF levels with lower percentages of female participants (Q = 40.15, df = 6, p < 0.001) and a skewed scatter plot toward a greater impact using higher (poly)phenols doses. Conclusion: This review suggests that age group, gender, the used phenolic compounds, their human bioavailability rate, and the supplementation dose as the primary moderator variables relating to the beneficial effects of (poly)phenol consumption on cognitive and brain function in humans. Therefore, it seems more advantageous to start anti-aging (poly)phenol interventions in adults earlier in life using medium (≈500 mg) to high doses (≈1000 mg) of phenolic compounds, with at least medium bioavailability rate (≥9%). Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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19 pages, 3428 KiB  
Review
Chemical Composition, Bioactivity and Safety Aspects of Kuding Tea—From Beverage to Herbal Extract
by Svenja Wüpper, Kai Lüersen and Gerald Rimbach
Nutrients 2020, 12(9), 2796; https://doi.org/10.3390/nu12092796 - 12 Sep 2020
Cited by 15 | Viewed by 7473
Abstract
Kuding tea (KT) is a bitter-tasting herbal tea that has been commonly used in traditional Chinese medicine (TCM). The large-leaved Ku-Ding-Cha (Aquifoliaceae) is composed of its representative species Ilex latifolia Thunb and Ilex kudingcha C.J. Tseng. Because of its potential lipid-lowering, body weight-reducing [...] Read more.
Kuding tea (KT) is a bitter-tasting herbal tea that has been commonly used in traditional Chinese medicine (TCM). The large-leaved Ku-Ding-Cha (Aquifoliaceae) is composed of its representative species Ilex latifolia Thunb and Ilex kudingcha C.J. Tseng. Because of its potential lipid-lowering, body weight-reducing and blood-glucose-lowering properties, KT has increasingly been recognised for its importance over the past several decades. KT is no longer used only as a beverage, and various extraction methods have been applied to obtain aqueous and ethanolic KT extracts (KTE) or their fractions, which could potentially be used as dietary supplements. The major bioactive components of KT are triterpene saponins and polyphenols, but the composition of KT differs substantially between and among the different KT species. This in turn might affect the physiological effects of KT. KT exhibits antiobesity properties, possibly partly by affecting the intestinal microbiota. In addition, KT may mediate putative antioxidative, anti-inflammatory and anticancer activities. However, there is evidence that high KTE supplementation can adversely affect liver metabolism. The physiological relevance of KT in humans remains rather unclear since the potential health benefits of KT and its constituents reviewed here are mainly derived on the basis of in vitro and animal studies. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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30 pages, 1432 KiB  
Review
Natural Sources, Pharmacokinetics, Biological Activities and Health Benefits of Hydroxycinnamic Acids and Their Metabolites
by Matej Sova and Luciano Saso
Nutrients 2020, 12(8), 2190; https://doi.org/10.3390/nu12082190 - 23 Jul 2020
Cited by 97 | Viewed by 7582
Abstract
Hydroxycinnamic acids (HCAs) are important natural phenolic compounds present in high concentrations in fruits, vegetables, cereals, coffee, tea and wine. Many health beneficial effects have been acknowledged in food products rich in HCAs; however, food processing, dietary intake, bioaccessibility and pharmacokinetics have a [...] Read more.
Hydroxycinnamic acids (HCAs) are important natural phenolic compounds present in high concentrations in fruits, vegetables, cereals, coffee, tea and wine. Many health beneficial effects have been acknowledged in food products rich in HCAs; however, food processing, dietary intake, bioaccessibility and pharmacokinetics have a high impact on HCAs to reach the target tissue in order to exert their biological activities. In particular, metabolism is of high importance since HCAs’ metabolites could either lose the activity or be even more potent compared to the parent compounds. In this review, natural sources and pharmacokinetic properties of HCAs and their esters are presented and discussed. The main focus is on their metabolism along with biological activities and health benefits. Special emphasis is given on specific effects of HCAs’ metabolites in comparison with their parent compounds. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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22 pages, 1304 KiB  
Review
The Effects and Potential Mechanism of Oil Palm Phenolics in Cardiovascular Health: A Review on Current Evidence
by Nurul ‘Izzah Ibrahim, Syed Fairus and Isa Naina Mohamed
Nutrients 2020, 12(7), 2055; https://doi.org/10.3390/nu12072055 - 10 Jul 2020
Cited by 8 | Viewed by 3386
Abstract
Cardiovascular disease (CVD) is globally known as the number one cause of death with hyperlipidemia as a strong risk factor for CVD. The initiation of drug treatment will be recommended if lifestyle modification fails. However, medicines currently used for improving cholesterol and low-density [...] Read more.
Cardiovascular disease (CVD) is globally known as the number one cause of death with hyperlipidemia as a strong risk factor for CVD. The initiation of drug treatment will be recommended if lifestyle modification fails. However, medicines currently used for improving cholesterol and low-density lipoprotein cholesterols (LDL-C) levels have been associated with various side effects. Thus, alternative treatment with fewer or no side effects needs to be explored. A potential agent, oil palm phenolics (OPP) recovered from the aqueous waste of oil palm milling process contains numerous water-soluble phenolic compounds. It has been postulated that OPP has shown cardioprotective effects via several mechanisms such as cholesterol biosynthesis pathway, antioxidant and anti-inflammatory properties. This review aims to summarize the current evidence explicating the actions of OPP in cardiovascular health and the mechanisms that maybe involved for the cardioprotective effects. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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32 pages, 1027 KiB  
Review
Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research
by Assylzhan Yessenkyzy, Timur Saliev, Marina Zhanaliyeva, Abdul-Razak Masoud, Bauyrzhan Umbayev, Shynggys Sergazy, Elena Krivykh, Alexander Gulyayev and Talgat Nurgozhin
Nutrients 2020, 12(5), 1344; https://doi.org/10.3390/nu12051344 - 08 May 2020
Cited by 61 | Viewed by 11284
Abstract
It has been thought that caloric restriction favors longevity and healthy aging where autophagy plays a vital role. However, autophagy decreases during aging and that can lead to the development of aging-associated diseases such as cancer, diabetes, neurodegeneration, etc. It was shown that [...] Read more.
It has been thought that caloric restriction favors longevity and healthy aging where autophagy plays a vital role. However, autophagy decreases during aging and that can lead to the development of aging-associated diseases such as cancer, diabetes, neurodegeneration, etc. It was shown that autophagy can be induced by mechanical or chemical stress. In this regard, various pharmacological compounds were proposed, including natural polyphenols. Apart from the ability to induce autophagy, polyphenols, such as resveratrol, are capable of modulating the expression of pro- and anti-apoptotic factors, neutralizing free radical species, affecting mitochondrial functions, chelating redox-active transition metal ions, and preventing protein aggregation. Moreover, polyphenols have advantages compared to chemical inducers of autophagy due to their intrinsic natural bio-compatibility and safety. In this context, polyphenols can be considered as a potential therapeutic tool for healthy aging either as a part of a diet or as separate compounds (supplements). This review discusses the epigenetic aspect and the underlying molecular mechanism of polyphenols as an anti-aging remedy. In addition, the recent advances of studies on NAD-dependent deacetylase sirtuin-1 (SIRT1) regulation of autophagy, the role of senescence-associated secretory phenotype (SASP) in cells senescence and their regulation by polyphenols have been highlighted as well. Apart from that, the review also revised the latest information on how polyphenols can help to improve mitochondrial function and modulate apoptosis (programmed cell death). Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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21 pages, 657 KiB  
Review
Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review
by Gaber El-Saber Batiha, Amany Magdy Beshbishy, Lamiaa G. Wasef, Yaser H. A. Elewa, Ahmed A. Al-Sagan, Mohamed E. Abd El-Hack, Ayman E. Taha, Yasmina M. Abd-Elhakim and Hari Prasad Devkota
Nutrients 2020, 12(3), 872; https://doi.org/10.3390/nu12030872 - 24 Mar 2020
Cited by 420 | Viewed by 37487
Abstract
Medicinal plants have been used from ancient times for human healthcare as in the form of traditional medicines, spices, and other food components. Garlic (Allium sativum L.) is an aromatic herbaceous plant that is consumed worldwide as food and traditional remedy for [...] Read more.
Medicinal plants have been used from ancient times for human healthcare as in the form of traditional medicines, spices, and other food components. Garlic (Allium sativum L.) is an aromatic herbaceous plant that is consumed worldwide as food and traditional remedy for various diseases. It has been reported to possess several biological properties including anticarcinogenic, antioxidant, antidiabetic, renoprotective, anti-atherosclerotic, antibacterial, antifungal, and antihypertensive activities in traditional medicines. A. sativum is rich in several sulfur-containing phytoconstituents such as alliin, allicin, ajoenes, vinyldithiins, and flavonoids such as quercetin. Extracts and isolated compounds of A. sativum have been evaluated for various biological activities including antibacterial, antiviral, antifungal, antiprotozoal, antioxidant, anti-inflammatory, and anticancer activities among others. This review examines the phytochemical composition, pharmacokinetics, and pharmacological activities of A. sativum extracts as well as its main active constituent, allicin. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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14 pages, 956 KiB  
Review
A Review on Sources and Pharmacological Aspects of Sakuranetin
by Monika Stompor
Nutrients 2020, 12(2), 513; https://doi.org/10.3390/nu12020513 - 18 Feb 2020
Cited by 54 | Viewed by 4588
Abstract
Sakuranetin belongs to the group of methoxylated flavanones. It is widely distributed in Polyomnia fruticosa and rice, where it acts as a phytoalexin. Other natural sources of this compound are, among others, grass trees, shrubs, flowering plants, cheery, and some herbal drugs, where [...] Read more.
Sakuranetin belongs to the group of methoxylated flavanones. It is widely distributed in Polyomnia fruticosa and rice, where it acts as a phytoalexin. Other natural sources of this compound are, among others, grass trees, shrubs, flowering plants, cheery, and some herbal drugs, where it has been found in the form of glycosides (mainly sakuranin). Sakuranetin has antiproliferative activity against human cell lines typical for B16BL6 melanoma, esophageal squamous cell carcinoma (ESCC) and colon cancer (Colo 320). Moreover, sakuranetin shows antiviral activity towards human rhinovirus 3 and influenza B virus and was reported to have antioxidant, antimicrobial, antiinflammatory, antiparasitic, antimutagenic, and antiallergic properties. The aim of this review is to present the current status of knowledge of pro-health properties of sakuranetin. Full article
(This article belongs to the Special Issue Dietary (Poly)Phenols and Health)
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