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El-Saadony MT, Yang T, Saad AM, Alkafaas SS, Elkafas SS, Eldeeb GS, Mohammed DM, Salem HM, Korma SA, Loutfy SA, Alshahran MY, Ahmed AE, Mosa WFA, Abd El-Mageed TA, Ahmed AF, Fahmy MA, El-Tarabily MK, Mahmoud RM, AbuQamar SF, El-Tarabily KA, Lorenzo JM. Polyphenols: Chemistry, bioavailability, bioactivity, nutritional aspects and human health benefits: A review. Int J Biol Macromol 2024; 277:134223. [PMID: 39084416 DOI: 10.1016/j.ijbiomac.2024.134223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 06/17/2024] [Accepted: 07/26/2024] [Indexed: 08/02/2024]
Abstract
Polyphenols, including phenolics, alkaloids, and terpenes, are secondary metabolites that are commonly found in fruits, vegetables, and beverages, such as tea, coffee, wine, chocolate, and beer. These compounds have gained considerable attention and market demand because of their potential health benefits. However, their application is limited due to their low absorption rates and reduced tissue distribution efficiency. Engineering polyphenol-protein complexes or conjugates can enhance the antioxidant properties, bioavailability, and stability of polyphenols and improve digestive enzyme hydrolysis, target-specific delivery, and overall biological functions. Complex polyphenols, such as melanin, tannins, and ellagitannins, can promote gut microbiota balance, bolster antioxidant defense, and improve overall human health. Despite these benefits, the safety of polyphenol complexes must be thoroughly evaluated before their use as functional food additives or supplements. This review provides a detailed overview of the types of macromolecular polyphenols, their chemical composition, and their role in food enrichment. The mechanisms by which complex polyphenols act as antioxidative, anti-inflammatory, and anticancer agents have also been discussed.
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Affiliation(s)
- Mohamed T El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Tao Yang
- Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou, 571199, China
| | - Ahmed M Saad
- Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Samar Sami Alkafaas
- Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Sara Samy Elkafas
- Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University, Shebin El Kom, 32511, Egypt; Faculty of Control System and Robotics, Information Technologies, Mechanics and Optics (ITMO) University, Saint-Petersburg, Russia
| | - Gehad S Eldeeb
- Department of Food Technology, Faculty of Agriculture, Suez Canal University, Ismailia, 41522, Egypt
| | - Dina Mostafa Mohammed
- Nutrition and Food Sciences Department, National Research Centre, Dokki, Giza, 12622, Egypt
| | - Heba M Salem
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Sameh A Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Samah A Loutfy
- Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 12211, Egypt
| | - Mohammad Y Alshahran
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, 9088, Saudi Arabia
| | - Ahmed Ezzat Ahmed
- Department of Biology, College of Science, King Khalid University, Abha, 61421, Saudi Arabia
| | - Walid F A Mosa
- Plant Production Department (Horticulture-Pomology), Faculty of Agriculture, Saba Basha, Alexandria University, Alexandria, 21531, Egypt
| | - Taia A Abd El-Mageed
- Soil and Water Department, Faculty of Agriculture, Fayoum University, Fayoum, 63514, Egypt
| | - Atef F Ahmed
- Department of Biology, College of Science, Taif University, Taif, 21944, Saudi Arabia
| | - Mohamed A Fahmy
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | | | - Reda M Mahmoud
- Dr Nutrition Pharmaceuticals (DNP), Dubai, 48685, United Arab Emirates
| | - Synan F AbuQamar
- Department of Biology, United Arab Emirates University, Al Ain, 15551, United Arab Emirates.
| | - Khaled A El-Tarabily
- Department of Biology, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; Harry Butler Institute, Murdoch University, Murdoch, 6150, W.A., Australia
| | - José M Lorenzo
- Centro Tecnologico´ de La Carne de Galicia, Rúa Galicia No. 4, Parque Tecnologico de Galicia, San Cibrao das Vinas, Ourense, 32900, Spain; Universidad de Vigo, Area´ de Tecnología de Los Alimentos, Facultad de Ciencias de Ourense, Ourense, 32004, Spain
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Ficco DBM, Petroni K, Mistura L, D'Addezio L. Polyphenols in Cereals: State of the Art of Available Information and Its Potential Use in Epidemiological Studies. Nutrients 2024; 16:2155. [PMID: 38999902 PMCID: PMC11243113 DOI: 10.3390/nu16132155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/25/2024] [Accepted: 07/04/2024] [Indexed: 07/14/2024] Open
Abstract
Cereals are the basis of much of the world's daily diet. Recently, there has been considerable interest in the beneficial properties of wholegrains due to their content of phytochemicals, particularly polyphenols. Despite this, the existing data on polyphenolic composition of cereal-based foods reported in the most comprehensive databases are still not updated. Many cereal-based foods and phenolic compounds are missing, including pigmented ones. Observational epidemiological studies reporting the intake of polyphenols from cereals are limited and inconsistent, although experimental studies suggest a protective role for dietary polyphenols against cardiovascular disease, diabetes, and cancer. Estimating polyphenol intake is complex because of the large number of compounds present in foods and the many factors that affect their levels, such as plant variety, harvest season, food processing and cooking, making it difficult matching consumption data with data on food composition. Further, it should be taken into account that food composition tables and consumed foods are categorized in different ways. The present work provides an overview of the available data on polyphenols content reported in several existing databases, in terms of presence, missing and no data, and discusses the strengths and weaknesses of methods for assessing cereal polyphenol consumption. Furthermore, this review suggests a greater need for the inclusion of most up-to-date cereal food composition data and for the harmonization of standardized procedures in collecting cereal-based food data and adequate assessment tools for dietary intake.
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Affiliation(s)
- Donatella Bianca Maria Ficco
- Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria (CREA)-Centro di Ricerca Cerealicoltura e Colture Industriali, S.S. 673 m 25200, 71122 Foggia, Italy
| | - Katia Petroni
- Dipartimento di Bioscienze, Università degli Studi di Milano, Via Celoria, 26, 20133 Milan, Italy
| | - Lorenza Mistura
- Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria (CREA)-Centro di Ricerca Alimenti e Nutrizione, Via Ardeatina 546, 00178 Roma, Italy
| | - Laura D'Addezio
- Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria (CREA)-Centro di Ricerca Alimenti e Nutrizione, Via Ardeatina 546, 00178 Roma, Italy
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Lessard-Lord J, Roussel C, Guay V, Desjardins Y. Characterization of the Interindividual Variability Associated with the Microbial Metabolism of (-)-Epicatechin. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:13814-13827. [PMID: 37683128 PMCID: PMC10516121 DOI: 10.1021/acs.jafc.3c05491] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Revised: 08/25/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023]
Abstract
Although the relationship between gut microbiota and flavan-3-ol metabolism differs greatly between individuals, the specific metabolic profiles, known as metabotypes, have not yet been clearly defined. In this study, fecal batch fermentations of 34 healthy donors inoculated with (-)-epicatechin were stratified into groups based on their conversion rate of (-)-epicatechin and their quali-quantitative metabolic profile. Fast and slow converters of (-)-epicatechin, high producers of 1-(3'-hydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol (3-HPP-2-ol) and 5-(3',4'-dihydroxyphenyl)-γ-valerolactone (3,4-DHPVL) were identified. Fecal microbiota analysis revealed that fast conversion of (-)-epicatechin was associated with short-chain fatty acid (SCFA)-producing bacteria, such as Faecalibacterium spp. and Bacteroides spp., and higher levels of acetate, propionate, butyrate, and valerate were observed for fast converters. Other bacteria were associated with the conversion of 1-(3',4'-dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)-propan-2-ol into 3-HPP-2-ol (Lachnospiraceae UCG-010 spp.) and 3,4-DHPVL (Adlercreutzia equolifaciens). Such stratification sheds light on the mechanisms of action underlying the high interindividual variability associated with the health benefits of flavan-3-ols.
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Affiliation(s)
- Jacob Lessard-Lord
- Institute
of Nutrition and Functional Foods (INAF), Faculty of Agriculture and
Food Sciences, Laval University, 2440 Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
- Nutrition,
Health and Society Centre (NUTRISS), INAF, Laval University, 2440
Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
- Department
of Plant Science, Faculty of Agriculture and Food Sciences, Laval University, 2425 Rue de l’Agriculture, Québec, Quebec, Canada G1V 0A6
| | - Charlène Roussel
- Institute
of Nutrition and Functional Foods (INAF), Faculty of Agriculture and
Food Sciences, Laval University, 2440 Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
- Nutrition,
Health and Society Centre (NUTRISS), INAF, Laval University, 2440
Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
- Canada
Excellence Research Chair on the Microbiome-Endocannabinoidome Axis
in Metabolic Health, Laval University, 2440 Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
| | - Valérie Guay
- Institute
of Nutrition and Functional Foods (INAF), Faculty of Agriculture and
Food Sciences, Laval University, 2440 Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
- Nutrition,
Health and Society Centre (NUTRISS), INAF, Laval University, 2440
Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
| | - Yves Desjardins
- Institute
of Nutrition and Functional Foods (INAF), Faculty of Agriculture and
Food Sciences, Laval University, 2440 Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
- Nutrition,
Health and Society Centre (NUTRISS), INAF, Laval University, 2440
Boulevard Hochelaga, Québec, Quebec, Canada G1V 0A6
- Department
of Plant Science, Faculty of Agriculture and Food Sciences, Laval University, 2425 Rue de l’Agriculture, Québec, Quebec, Canada G1V 0A6
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Medic A, Kunc P, Zamljen T, Hudina M, Veberic R, Solar A. Identification and Quantification of the Major Phenolic Constituents in Castanea sativa and Commercial Interspecific Hybrids ( C. sativa x C. crenata) Chestnuts Using HPLC-MS/MS. Int J Mol Sci 2023; 24:13086. [PMID: 37685892 PMCID: PMC10488303 DOI: 10.3390/ijms241713086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/16/2023] [Accepted: 08/20/2023] [Indexed: 09/10/2023] Open
Abstract
Due to the lack of studies on chestnut metabolites, this study was conducted to identify and quantify the major phenolic constituents in chestnuts. Data were compared with the three most commonly grown interspecific hybrids of C. sativa and C. crenata ('Bouche de Betizac', 'Marsol', and 'Maraval') and three "native" accessions of C. sativa. High-performance liquid chromatography coupled with mass spectrometry was used to identify and quantify these compounds. Four dicarboxylic acid derivatives, five hydroxybenzoic acids, nine hydroxycinnamic acids, and three flavanols were identified and quantified, most of them for the first time. Hydroxybenzoic acids were the major phenolic compounds in all chestnut cultivars/accessions, followed by flavanols, dicarboxylic acid derivatives, and hydroxycinnamic acids. Of all the compounds studied, the (epi)catechin dimer was the most abundant in chestnut. The assumption that cultivars from commercial hybrids have a better and different metabolic profile than "native" accessions was refuted.
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Affiliation(s)
- Aljaz Medic
- Biotechnical Faculty, Department of Agronomy, University of Ljubljana, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia; (P.K.); (M.H.)
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Medic A, Solar A, Hudina M, Veberic R, Zamljen T. Effect of Different Walnut and Hazelnut Leaf Compost Treatments on Yield and Phenolic Composition of Lactuca sativa L. Foods 2023; 12:2738. [PMID: 37509831 PMCID: PMC10379347 DOI: 10.3390/foods12142738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/11/2023] [Accepted: 07/17/2023] [Indexed: 07/30/2023] Open
Abstract
The use of compost made from the leaves of Juglans regia has long been controversial because of its inhibitory effect due to the presence of juglone. Therefore, the aim of our study was to replicate the typical habits of farmers and gardeners, where the dried leaves are collected at the end of the season and placed in a composter. Then, the effects of the different treatments on the yield of the plant (lettuce), secondary metabolism, and possible toxicity of the compost of the grown plant were evaluated. The lowest yield of lettuce was obtained in soil with composted walnut and hazelnut leaves, while the highest yield was recorded in in soil with compost control, soil with composted walnut leaves and grass with the addition of composting agent and soil with composted walnut leaves with addition of composting agent. Some allelochemicals were still present in the compost but at such low levels that they did not affect yield. We suggest that dry walnut leaves and cut grass can be used for composting, while dry hazelnut leaves still contain some allelochemicals after two years that significantly inhibit plant growth and thus yield, so we would not recommend their use for composting.
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Affiliation(s)
- Aljaz Medic
- Department of Agronomy, Biotechnical Faculty, University of Ljubljana, SI 1000 Ljubljana, Slovenia
| | - Anita Solar
- Department of Agronomy, Biotechnical Faculty, University of Ljubljana, SI 1000 Ljubljana, Slovenia
| | - Metka Hudina
- Department of Agronomy, Biotechnical Faculty, University of Ljubljana, SI 1000 Ljubljana, Slovenia
| | - Robert Veberic
- Department of Agronomy, Biotechnical Faculty, University of Ljubljana, SI 1000 Ljubljana, Slovenia
| | - Tilen Zamljen
- Department of Agronomy, Biotechnical Faculty, University of Ljubljana, SI 1000 Ljubljana, Slovenia
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Yao Y, Feng S, Li X, Liu T, Ye S, Ma L, Man S. Litchi procyanidins inhibit colon cancer proliferation and metastasis by triggering gut-lung axis immunotherapy. Cell Death Dis 2023; 14:109. [PMID: 36774343 PMCID: PMC9922286 DOI: 10.1038/s41419-022-05482-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Revised: 11/24/2022] [Accepted: 11/28/2022] [Indexed: 02/13/2023]
Abstract
Litchi chinensis seed, as a valuable by-product of the subtropical fruit litchi (Litchi chinensis Sonn.), has been confirmed to be rich in procyanidins (LPC). The anticarcinogenic properties of procyanidins has been primarily attributed to their antioxidant and anti-inflammatory activities. However, there is a comparative paucity of information on if and how LPC inhibits colon cancer. Here, LPC significantly inhibited CT26 colon cancer cells proliferation and metastasis in vivo and in vitro. In CT26 lung metastatic mice, the anti-metastatic effect of LPC relied on its regulation of gut microbiota such as increase of Lachnospiraceae UCG-006, Ruminococcus, and their metabolites such as acetic acid, propionic acid and butyric acid. In addition, LPC significantly inhibited CT26 colon cancer cells metastasis through increasing CD8+ cytotoxic T lymphocytes infiltration and decreasing the number of macrophages. Antibiotics treatment demonstrated that the therapeutic effect of LPC depended on the gut microbiota, which regulated T cells immune response. Taken together, LPC had strong inhibitory effects on colon cancer pulmonary metastasis by triggering gut-lung axis to influence the T cells immune response. Our research provides a novel finding for the utilization of procyanidins in the future, that is, supplementing more fruits and vegetables rich in procyanidins is beneficial to the treatment of colon cancer, or it can be used as an adjuvant drug in clinical anti-tumor immunotherapy.
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Affiliation(s)
- Yuan Yao
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China
| | - Suya Feng
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China
| | - Xuejiao Li
- Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Taohua Liu
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China
| | - Shengying Ye
- Department of Pharmacy, The 983th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Tianjin, 300142, China.
| | - Long Ma
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
| | - Shuli Man
- State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China.
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Di Pede G, Mena P, Bresciani L, Almutairi TM, Del Rio D, Clifford MN, Crozier A. Human colonic catabolism of dietary flavan-3-ol bioactives. Mol Aspects Med 2023; 89:101107. [PMID: 35931563 DOI: 10.1016/j.mam.2022.101107] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 02/04/2023]
Abstract
Understanding the fate of ingested polyphenols is crucial in elucidating the molecular mechanisms underlying the beneficial effects of a fruit and vegetable-based diet. This review focuses on the colon microbiota-mediated transformation of the flavan-3-ols and the structurally related procyanidins found in dietary plant foods and beverages, plus the flavan-3-ol-derived theaflavins of black tea, and the post-absorption phase II metabolism of the gut microbiota catabolites. Despite significant advances in the last decade major analytical challenges remain. Strategies to address them are presented.
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Affiliation(s)
- Giuseppe Di Pede
- Human Nutrition Unit, Department of Food and Drug, University of Parma, 43125, Parma, Italy
| | - Pedro Mena
- Human Nutrition Unit, Department of Food and Drug, University of Parma, 43125, Parma, Italy; Microbiome Research Hub, University of Parma, 43124, Parma, Italy
| | - Letizia Bresciani
- Human Nutrition Unit, Department of Food and Drug, University of Parma, 43125, Parma, Italy
| | - Tahani M Almutairi
- Department of Chemistry, King Saud University, Riyadh, 11363, Saudi Arabia
| | - Daniele Del Rio
- Human Nutrition Unit, Department of Food and Drug, University of Parma, 43125, Parma, Italy; Microbiome Research Hub, University of Parma, 43124, Parma, Italy
| | - Michael N Clifford
- School of Bioscience and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK; Department of Nutrition, Dietetics, and Food, School of Clinical Sciences at Monash Health, Faculty of Medicine Nursing and Health Sciences, Monash University, Notting Hill, Victoria, 3168, Australia
| | - Alan Crozier
- Department of Chemistry, King Saud University, Riyadh, 11363, Saudi Arabia; School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, G12 8QQ, United Kingdom.
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NAUREEN ZAKIRA, MEDORI MARIACHIARA, DHULI KRISTJANA, DONATO KEVIN, CONNELLY STEPHENTHADDEUS, BELLINATO FRANCESCO, GISONDI PAOLO, BERTELLI MATTEO. Polyphenols and Lactobacillus reuteri in oral health. JOURNAL OF PREVENTIVE MEDICINE AND HYGIENE 2022; 63:E246-E254. [PMID: 36479495 PMCID: PMC9710395 DOI: 10.15167/2421-4248/jpmh2022.63.2s3.2767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Oral health is one of the necessary preludes to the overall quality of life. Several medical procedures and therapies are available to treat oral diseases in general and periodontal diseases in particular, yet caries, periodontitis, oral cancer, and oral infections remain a global concern. Natural molecules, with their anti-oxidant, anti-inflammatory, and anti-microbic properties, are one of the main sources of oral health and dental health care, and should be supplemented to exploit their beneficial effects. A possible way to improve the intake of these molecules is adhering to a diet that is rich in fruits, vegetables, and probiotics, which has many beneficial properties and can improve overall health and wellbeing. The Mediterranean diet, in particular, provides several beneficial natural molecules, mainly because of the precious nutrients contained in its typical ingredients, mainly plant-based (olives, wine, citrus fruits, and many more). Its beneficial effects on several diseases and in increasing the overall wellbeing of the population are currently being studied by physicians. Among its nutrients, polyphenols (including, among other molecules, lignans, tannins, and flavonoids) seem to be of outmost importance: several studies showed their anticariogenic properties, as well as their effects in decreasing the incidence of non-communicable diseases. Therefore, plant-derived molecules - such as polyphenols - and probiotics - such as Lactobacillus reuteri - have shown a significant potential in treating and curing oral diseases, either alone or in combination, owing to their antioxidant and antimicrobial properties, respectively.
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Affiliation(s)
| | | | - KRISTJANA DHULI
- MAGI’S LAB, Rovereto (TN), Italy
- Correspondence: Kristjana Dhuli, MAGI’S LAB, Rovereto (TN), 38068, Italy; E-mail:
| | | | | | - FRANCESCO BELLINATO
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - PAOLO GISONDI
- Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
| | - MATTEO BERTELLI
- MAGI Euregio, Bolzano, Italy
- MAGI’S LAB, Rovereto (TN), Italy
- MAGISNAT, Peachtree Corners (GA), USA
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Kampa RP, Flori L, Sęk A, Spezzini J, Brogi S, Szewczyk A, Calderone V, Bednarczyk P, Testai L. Luteolin-Induced Activation of Mitochondrial BK Ca Channels: Undisclosed Mechanism of Cytoprotection. Antioxidants (Basel) 2022; 11:1892. [PMID: 36290615 PMCID: PMC9598376 DOI: 10.3390/antiox11101892] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 09/29/2023] Open
Abstract
Luteolin (LUT) is a well-known flavonoid that exhibits a number of beneficial properties. Among these, it shows cardioprotective effects, as confirmed by numerous studies. However, its effect on mitochondrial potassium channels, the activation of which is related to cytoprotection, as well as on heart ischemia/reperfusion (I/R) damage prevention, has not yet been investigated. The large conductance calcium-regulated potassium channel (mitoBKCa) has been identified in both the mitochondria of the vascular endothelial cells, which plays a significant role in the functioning of the cardiovascular system under oxidative stress-related conditions, and in the mitochondria of cardiomyocytes, where it is deeply involved in cardiac protection against I/R injury. Therefore, the aim of this study was to explore the role of the mitoBKCa channel in luteolin-induced cytoprotection. A number of in vitro, in vivo, ex vivo and in silico studies have confirmed that luteolin activates this channel in the mitochondria of cardiomyocytes and endothelial cells, which in turn leads to the protection of the endothelium and a significant reduction in the extent of damage resulting from myocardial infarction, where this effect was partially abolished by the mitoBKCa channel blocker paxilline. In conclusion, these results suggest that luteolin has cardioprotective effects, at least in part, through the activation of the mitoBKCa channel, shedding light on a new putative mechanism of action.
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Affiliation(s)
- Rafał P. Kampa
- Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland
- Department of Pharmacology, Faculty of Pharmacy, University of Pisa, 6 via Bonanno Pisano, 56120 Pisa, Italy
| | - Lorenzo Flori
- Department of Pharmacology, Faculty of Pharmacy, University of Pisa, 6 via Bonanno Pisano, 56120 Pisa, Italy
| | - Aleksandra Sęk
- Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland
| | - Jacopo Spezzini
- Department of Pharmacology, Faculty of Pharmacy, University of Pisa, 6 via Bonanno Pisano, 56120 Pisa, Italy
| | - Simone Brogi
- Department of Pharmacology, Faculty of Pharmacy, University of Pisa, 6 via Bonanno Pisano, 56120 Pisa, Italy
| | - Adam Szewczyk
- Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland
| | - Vincenzo Calderone
- Department of Pharmacology, Faculty of Pharmacy, University of Pisa, 6 via Bonanno Pisano, 56120 Pisa, Italy
| | - Piotr Bednarczyk
- Department of Physics and Biophysics, Institute of Biology, Warsaw University of Life Sciences–SGGW (WULS-SGGW), 159 Nowoursynowska St., 02-776 Warsaw, Poland
| | - Lara Testai
- Department of Pharmacology, Faculty of Pharmacy, University of Pisa, 6 via Bonanno Pisano, 56120 Pisa, Italy
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Sesso HD, Manson JE, Aragaki AK, Rist PM, Johnson LG, Friedenberg G, Copeland T, Clar A, Mora S, Moorthy MV, Sarkissian A, Carrick WR, Anderson GL. Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. Am J Clin Nutr 2022; 115:1490-1500. [PMID: 35294962 PMCID: PMC9170467 DOI: 10.1093/ajcn/nqac055] [Citation(s) in RCA: 86] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 03/01/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Cocoa extract is a source of flavanols that favorably influence vascular risk factors in small and short-term trials, yet effects on clinical cardiovascular events are untested. OBJECTIVES We examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults. METHODS We conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major CVD and recently diagnosed cancer. The intervention phase was June 2015 through December 2020. This article reports on the cocoa extract intervention. Participants were randomly assigned to a cocoa extract supplement [500 mg flavanols/d, including 80 mg (-)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction (MI), stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. RESULTS During a median follow-up of 3.6 y, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; P = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, neutral for other individual cardiovascular endpoints, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality. Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns. CONCLUSIONS Cocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%. Potential reductions in total cardiovascular events were supported in per-protocol analyses. Additional research is warranted to clarify whether cocoa extract may reduce clinical cardiovascular events. This trial is registered at www.clinicaltrials.gov as NCT02422745.
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Affiliation(s)
- Howard D Sesso
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - JoAnn E Manson
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Aaron K Aragaki
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Pamela M Rist
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Lisa G Johnson
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Georgina Friedenberg
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Trisha Copeland
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Allison Clar
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Samia Mora
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - M Vinayaga Moorthy
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Ara Sarkissian
- Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - William R Carrick
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Garnet L Anderson
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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11
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Yousaf M, Razmovski-Naumovski V, Zubair M, Chang D, Zhou X. Synergistic Effects of Natural Product Combinations in Protecting the Endothelium Against Cardiovascular Risk Factors. J Evid Based Integr Med 2022; 27:2515690X221113327. [PMID: 35849068 PMCID: PMC9297466 DOI: 10.1177/2515690x221113327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The multi-component and multi-targeted approach of natural products have the potential to manage CVDs. This review aims to provide a comprehensive insight into the synergistic mechanism of natural product combinations in protecting the endothelium against various cardiovascular risk factors. Databases (PubMed, MEDLINE and EMBASE) and Google Scholar were searched, and studies in English published between January 2000 and February 2022 were collated. Clinical and pre-clinical studies of natural product combinations with or without pharmaceutical medicines, compared with monotherapy and/or proposing the underlying mechanism in protecting endothelial function, were included. Four clinical studies demonstrated that natural product combinations or natural product-pharmaceutical combinations improved endothelial function. This was associated with multi-targeted effects or improved absorption of the active substances in the body. Seventeen preclinical studies showed that natural product combinations produced synergistic (demonstrated by combination index or Bliss independence model) or enhanced effects in protecting the endothelium against hyperlipidemia, hypertension, diabetes mellitus, platelet activation, oxidative stress and hyperhomocysteinemia. The molecular targets included reactive oxygen species, Nrf2-HO-1, p38MAPK, P13K/Akt and NF-κB. Thus, the current available evidence of natural product combinations in targeting endothelial dysfunction is predominantly from preclinical studies. These have demonstrated synergistic/enhanced pharmacological activities and proposed associated mechanisms. However, evidence from larger, well-designed clinical trials remains weak. More cohesion is required between preclinical and clinical data to support natural product combinations in preventing or slowing the progression of CVDs.
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Affiliation(s)
- Muhammad Yousaf
- Department of Bioinformatics and Biotechnology, 72594Government College University, Faisalabad, Pakistan
| | - Valentina Razmovski-Naumovski
- NICM Health Research Institute, 6489Western Sydney University, Westmead, Australia.,South Western Sydney Clinical School, School of Medicine & Health, 7800University of New South Wales (UNSW), Sydney, Australia
| | - Muhammad Zubair
- Department of Bioinformatics and Biotechnology, 72594Government College University, Faisalabad, Pakistan
| | - Dennis Chang
- NICM Health Research Institute, 6489Western Sydney University, Westmead, Australia
| | - Xian Zhou
- NICM Health Research Institute, 6489Western Sydney University, Westmead, Australia
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12
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Development and validation of HPLC-MS 2 methodology for the accurate determination of C4-C8 B-type flavanols and procyanidins. Sci Rep 2021; 11:14761. [PMID: 34285271 PMCID: PMC8292358 DOI: 10.1038/s41598-021-93993-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Accepted: 06/27/2021] [Indexed: 12/16/2022] Open
Abstract
Cocoa flavanols and procyanidins (CFs), natural dietary bioactives, have been studied extensively over the past two decades for their potential health benefits. Research on their safety and efficacy is critically dependent upon on the ability to reliably characeterize the research materials that are utilized, and with growing consumer availability of CF-based products, reliable methods for the detection of potential adulteration are of increasing importance. This research focused on the development of a high performance liquid chromatography-tandem mass spectrometry method (HPLC-MS2) using primary standards and 13C-labelled procyanidins as internal standards. The ability of MS2 detection to discriminate A- and B-type procyanidins was demonstrated. Method performances were validated for degrees of polymerization up to four in seven model food matrices. Accuracy ranged from 90.9 to 125.4% and precision was < 10% at lower concentrations. Finally, the method was applied to cocoa-based samples and compared to the AOAC 2020.05 analytical protocol, supporting the use of NIST 8403 as reference material for HPLC-MS2 analysis.
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13
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Tanghe A, Heyman E, Vanden Wyngaert K, Van Ginckel A, Celie B, Rietzschel E, Calders P, Shadid S. Evaluation of blood pressure lowering effects of cocoa flavanols in diabetes mellitus: A systematic review and meta-analysis. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104399] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
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14
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Tanghe A, Celie B, Shadid S, Rietzschel E, Op 't Roodt J, Reesink KD, Heyman E, Calders P. Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension: A Protocol for an Acute, Randomized, Double-Blinded, Placebo-Controlled Cross-Over Trial. Front Cardiovasc Med 2021; 8:602086. [PMID: 33791343 PMCID: PMC8005536 DOI: 10.3389/fcvm.2021.602086] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 02/16/2021] [Indexed: 01/21/2023] Open
Abstract
Introduction: Patients with type 2 diabetes mellitus are at high risk to develop vascular complications resulting in high morbidity and mortality. Cocoa flavanols are promising nutraceuticals with possible beneficial vascular effects in humans. However, limited research is currently available on the vascular effects in a diabetic population with inconsistent results. Possible reasons for this inconsistency might be heterogeneity in the given intervention (dose per time and day, single dose vs. split-dose, placebo formula) and the studied population (blood pressure at baseline, duration of diabetes, use of vasoactive antihypertensive and antidiabetic drugs, sex). Therefore, we aimed to develop a randomized, double-blinded, placebo-controlled cross-over trial to investigate whether cocoa flavanols have an acute impact on blood pressure and vascular reactivity in patients with type 2 diabetes with and without arterial hypertension. Methods and Analysis: We will include participants in four groups: (i) patients with type 2 diabetes without arterial hypertension, (ii) patients with type 2 diabetes with arterial hypertension and 1 antihypertensive drug, (iii) non-diabetic participants with essential hypertension and 1 antihypertensive drug, and (iv) healthy controls. All participants will complete the same protocol on both testing days, consuming high-flavanol cocoa extract (790 mg flavanols) or placebo. Macrovascular endothelial function (flow-mediated dilation) and blood pressure will be measured before and after capsule ingestion. Forearm muscle vasoreactivity (near-infrared spectroscopy) and brachial artery blood flow (echo-doppler) will be assessed in response to a dynamic handgrip exercise test after capsule ingestion. Data will be analyzed with a random intercept model in mixed models. Clinical Trial Registration:www.Clinicaltrials.gov, identifier: NCT03722199.
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Affiliation(s)
- Anouk Tanghe
- Department of Rehabilitation Sciences, Ghent University, Ghent, Belgium.,Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France
| | - Bert Celie
- Department of Rehabilitation Sciences, Ghent University, Ghent, Belgium.,Faculty of Health Sciences, Sport, Exercise Medicine and Lifestyle Institute (SEMLI), University of Pretoria, Pretoria, South Africa
| | - Samyah Shadid
- Department of Endocrinology, Ghent University Hospital, Ghent, Belgium
| | - Ernst Rietzschel
- Department of Cardiology, Ghent University Hospital, Ghent, Belgium.,Department of Internal Medicine, Ghent University, Ghent, Belgium
| | - Jos Op 't Roodt
- School of Cardiovascular Diseases (CARIM), Maastricht University Medical Centre, Maastricht, Netherlands
| | - Koen D Reesink
- School of Cardiovascular Diseases (CARIM), Maastricht University Medical Centre, Maastricht, Netherlands
| | - Elsa Heyman
- Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369 - URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France
| | - Patrick Calders
- Department of Rehabilitation Sciences, Ghent University, Ghent, Belgium
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15
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Griffin LE, Essenmacher L, Racine KC, Iglesias-Carres L, Tessem JS, Smith SM, Neilson AP. Diet-induced obesity in genetically diverse collaborative cross mouse founder strains reveals diverse phenotype response and amelioration by quercetin treatment in 129S1/SvImJ, PWK/EiJ, CAST/PhJ, and WSB/EiJ mice. J Nutr Biochem 2021; 87:108521. [PMID: 33039581 DOI: 10.1016/j.jnutbio.2020.108521] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Revised: 09/17/2020] [Accepted: 09/30/2020] [Indexed: 12/13/2022]
Abstract
Significant evidence suggests protective effects of flavonoids against obesity in animal models, but these often do not translate to humans. One explanation for this disconnect is use of a few mouse strains (notably C57BL/6 J) in obesity studies. Obesity is a multifactorial disease. The underlying causes are not fully replicated by the high-fat C57BL/6 J model, despite phenotypic similarities. Furthermore, the impact of genetic factors on the activities of flavonoids is unknown. This study was designed to explore how diverse mouse strains respond to diet-induced obesity when fed a representative flavonoid. A subset of Collaborative Cross founder strains (males and females) were placed on dietary treatments (low-fat, high-fat, high-fat with quercetin, high-fat with quercetin and antibiotics) longitudinally. Diverse responses were observed across strains and sexes. Quercetin appeared to moderately blunt weight gain in male C57 and both sexes of 129S1/SvImJ mice, and slightly increased weight gain in female C57 mice. Surprisingly, quercetin dramatically blunted weight gain in male, but not female, PWK/PhJ mice. For female mice, quercetin blunted weight gain (relative to the high-fat phase) in CAST/PhJ, PWK/EiJ and WSB/EiJ mice compared to C57. Antibiotics did not generally result in loss of protective effects of quercetin. This highlights complex interactions between genetic factors, sex, obesity stimuli, and flavonoid intake, and the need to move away from single inbred mouse models to enhance translatability to diverse humans. These data justify use of genetically diverse Collaborative Cross and Diversity Outbred models which are emerging as invaluable tools in the field of personalized nutrition.
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Affiliation(s)
- Laura E Griffin
- Department of Food, Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina, USA
| | - Lauren Essenmacher
- Department of Food Science and Technology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
| | - Kathryn C Racine
- Department of Food, Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina, USA
| | - Lisard Iglesias-Carres
- Department of Food, Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina, USA
| | - Jeffery S Tessem
- Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, Utah, USA
| | - Susan M Smith
- Department of Nutrition, Nutrition Research Institute, The University of North Carolina at Chapel Hill, Kannapolis, North Carolina, USA
| | - Andrew P Neilson
- Department of Food, Bioprocessing and Nutrition Sciences, Plants for Human Health Institute, North Carolina State University, Kannapolis, North Carolina, USA.
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16
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Ottaviani JI, Britten A, Lucarelli D, Luben R, Mulligan AA, Lentjes MA, Fong R, Gray N, Grace PB, Mawson DH, Tym A, Wierzbicki A, Forouhi NG, Khaw KT, Schroeter H, Kuhnle GGC. Biomarker-estimated flavan-3-ol intake is associated with lower blood pressure in cross-sectional analysis in EPIC Norfolk. Sci Rep 2020; 10:17964. [PMID: 33087825 PMCID: PMC7578063 DOI: 10.1038/s41598-020-74863-7] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 10/06/2020] [Indexed: 12/18/2022] Open
Abstract
Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (- 1.9 (- 2.7; - 1.1) mmHg in men and - 2.5 (- 3.3; - 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.
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Affiliation(s)
| | - Abigail Britten
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | | | - Robert Luben
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | | | | | | | - Nicola Gray
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK
| | | | | | - Amy Tym
- LGC, Newmarket Road, Fordham, UK
| | | | - Nita G Forouhi
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Kay-Tee Khaw
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | | | - Gunter G C Kuhnle
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
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17
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Polyphenols as reactive carbonyl species scavengers-The solution to the current puzzle of polyphenols' health effects. Med Hypotheses 2020; 142:110144. [PMID: 32739604 DOI: 10.1016/j.mehy.2020.110144] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 07/17/2020] [Accepted: 07/24/2020] [Indexed: 11/20/2022]
Abstract
Evidence from epidemiological analysis confirmed the protective effects of polyphenol-rich foods or beverages from certain chronic diseases, however, a direct antioxidant effect is not fully feasible when considering for the real in vivo behavior of polyphenols. Polyphenols have a limited bioavailability and only low concentrations are present in the systemic circulation compared with other endogenous and exogenous antioxidants, besides, how polyphenol can enter tissue (especially brain) and cells were not answered yet. There is investigation showed that reactive carbonyl species (RCS), which accumulated in circulatory system and tissue, also plays a significant role in the etiology and progression of certain chronic diseases. In the effort of searching for nontoxic trapping agents of RCS from dietary sources, some natural polyphenols have been found to have reactivity with RCS, It should be realized that polyphenols are versatile bioactive rather than mere antioxidants. We present here the hypothesis that polyphenols acting as RCS scavengers maybe the supplementary and reasonable mechanism for the puzzle of polyphenols' health effects.
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18
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Juliano FF, Alvarenga JFR, Lamuela-Raventos RM, Massarioli AP, Lima LM, Santos RC, Alencar SM. Polyphenol analysis using high-resolution mass spectrometry allows differentiation of drought tolerant peanut genotypes. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2020; 100:721-731. [PMID: 31602648 DOI: 10.1002/jsfa.10075] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 09/15/2019] [Accepted: 09/16/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND Peanut (Arachis hypogaea L.) is an important economic food crop highly appreciated worldwide. Although peanut cultivation has been expanding to dry regions, with water stress during growth stages, current genotypes are not adapted to drought. This study aimed to identify and quantify the full range of polyphenols in five peanut genotypes with different degrees of drought tolerance developed by Embrapa (Brazil) using ultra-high-definition accurate-mass liquid chromatography-electrospray ionization-LTQ-Orbitrap-mass spectrometry. RESULTS Fifty-eight polyphenols of the classes hydroxybenzoic acids, hydroxycinnamic acids, flavanols, flavonols and flavanones were identified and quantified using high mass accuracy data and confirmed by tandem mass spectrometric experiments. High-definition mass spectrometric analyses revealed nine phenolic compounds that have never been reported in peanuts before. Polyphenol assessment using multivariate analysis allowed identification of the level of similarities among the five peanut genotypes studied. CONCLUSION Higher drought-tolerant genotypes exhibited higher content of flavonoids, which suggests a relationship between these compounds and drought tolerance traits. © 2019 Society of Chemical Industry.
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Affiliation(s)
- Fernanda F Juliano
- Department of Agri-food Industry, Food and Nutrition, 'Luiz de Queiroz' College of Agriculture, University of São Paulo, Piracicaba, Brazil
| | - José Fernando R Alvarenga
- Department of Food and Nutrition, School of Pharmaceutical Sciences, São Paulo State University-UNESP, Araraquara, Brazil
| | - Rosa Maria Lamuela-Raventos
- Department of Nutrition, Food Sciences and Gastronomy, XARTA, INSA-UB, School of Pharmacy and Food Sciences, University of Barcelona, Carrer de Prat de la Riba, Santa Coloma de Gramenet, Spain
| | - Adna P Massarioli
- Department of Agri-food Industry, Food and Nutrition, 'Luiz de Queiroz' College of Agriculture, University of São Paulo, Piracicaba, Brazil
| | - Liziane M Lima
- Embrapa Cotton, Brazilian Agricultural Research Corporation, Campina Grande, Brazil
| | - Roseane C Santos
- Embrapa Cotton, Brazilian Agricultural Research Corporation, Campina Grande, Brazil
| | - Severino M Alencar
- Department of Agri-food Industry, Food and Nutrition, 'Luiz de Queiroz' College of Agriculture, University of São Paulo, Piracicaba, Brazil
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19
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Mena P, Bresciani L, Brindani N, Ludwig IA, Pereira-Caro G, Angelino D, Llorach R, Calani L, Brighenti F, Clifford MN, Gill CIR, Crozier A, Curti C, Del Rio D. Phenyl-γ-valerolactones and phenylvaleric acids, the main colonic metabolites of flavan-3-ols: synthesis, analysis, bioavailability, and bioactivity. Nat Prod Rep 2019; 36:714-752. [PMID: 30468210 DOI: 10.1039/c8np00062j] [Citation(s) in RCA: 161] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to their parent dietary compounds, the flavan-3-ol monomers and proanthocyanidins. In this review, the role and prospects of PVLs and PVAs as key metabolites in the understanding of the health features of flavan-3-ols have been critically assessed. Among the topics covered, are proposals for a standardised nomenclature for PVLs and PVAs. The formation, bioavailability and pharmacokinetics of PVLs and PVAs from different types of flavan-3-ols are discussed, taking into account in vitro and animal studies, as well as inter-individual differences and the existence of putative flavan-3-ol metabotypes. Synthetic strategies used for the preparation of PVLs are considered and the methodologies for their identification and quantification assessed. Metabolomic approaches unravelling the role of PVLs and PVAs as biomarkers of intake are also described. Finally, the biological activity of these microbial catabolites in different experimental models is summarised. Knowledge gaps and future research are considered in this key area of dietary (poly)phenol research.
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Affiliation(s)
- Pedro Mena
- Department of Food & Drugs, University of Parma, Via Volturno 39, 43125 Parma, Italy.
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20
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Guardado Yordi E, Koelig R, Matos MJ, Pérez Martínez A, Caballero Y, Santana L, Pérez Quintana M, Molina E, Uriarte E. Artificial Intelligence Applied to Flavonoid Data in Food Matrices. Foods 2019; 8:E573. [PMID: 31739559 PMCID: PMC6915672 DOI: 10.3390/foods8110573] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/25/2019] [Accepted: 10/29/2019] [Indexed: 11/30/2022] Open
Abstract
Increasing interest in constituents and dietary supplements has created the need for more efficient use of this information in nutrition-related fields. The present work aims to obtain optimal models to predict the total antioxidant properties of food matrices, using available information on the amount and class of flavonoids present in vegetables. A new dataset using databases that collect the flavonoid content of selected foods has been created. Structural information was obtained using a structural-topological approach called TOPological Sub-Structural Molecular (TOPSMODE). Different artificial intelligence algorithms were applied, including Machine Learning (ML) methods. The study allowed us to demonstrate the effectiveness of the models using structural-topological characteristics of dietary flavonoids. The proposed models can be considered, without overfitting, effective in predicting new values of Oxygen Radical Absorption capacity (ORAC), except in the Multi-Layer Perceptron (MLP) algorithm. The best optimal model was obtained by the Random Forest (RF) algorithm. The in silico methodology we developed allows us to confirm the effectiveness of the obtained models, by introducing the new structural-topological attributes, as well as selecting those that most influence the class variable.
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Affiliation(s)
- Estela Guardado Yordi
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Raúl Koelig
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
| | - Maria J. Matos
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- CIQUP/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal
| | - Amaury Pérez Martínez
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
- Facultad de Ciencias de la Tierra, Universidad Estatal Amazónica, km 2 ½ vía Puyo a Tena (Paso Lateral), Puyo 032892-118, Ecuador
| | - Yailé Caballero
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
| | - Lourdes Santana
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Manuel Pérez Quintana
- Facultad de Ciencias de la Tierra, Universidad Estatal Amazónica, km 2 ½ vía Puyo a Tena (Paso Lateral), Puyo 032892-118, Ecuador
| | - Enrique Molina
- Facultad de Ciencias Aplicadas, Universidad de Camagüey Ignacio Agramonte Loynaz, Cincunvalación Norte km 5 1/2, 74650 Camagüey, Cuba
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Eugenio Uriarte
- Facultad de Farmacia, Campus vida, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- Instituto de Ciencias Químicas Aplicadas, Universidad Autónoma de Chile, Santiago 7500912, Chile
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21
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Ottaviani JI, Fong R, Kimball J, Ensunsa JL, Gray N, Vogiatzoglou A, Britten A, Lucarelli D, Luben R, Grace PB, Mawson DH, Tym A, Wierzbicki A, Smith AD, Wareham NJ, Forouhi NG, Khaw KT, Schroeter H, Kuhnle GGC. Evaluation of (-)-epicatechin metabolites as recovery biomarker of dietary flavan-3-ol intake. Sci Rep 2019; 9:13108. [PMID: 31511603 PMCID: PMC6739331 DOI: 10.1038/s41598-019-49702-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 08/29/2019] [Indexed: 12/16/2022] Open
Abstract
Data from dietary intervention studies suggest that intake of (−)-epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide. Here, we evaluate a series of structurally related (−)-epicatechin metabolites (SREM), particularly (−)-epicatechin-3′-glucuronide, (−)-epicatechin-3′-sulfate and 3′-O-methyl-(−)-epicatechin-5-sulfate (SREMB), as flavan-3-ol and (−)-epicatechin intake. SREMB in urine proved to be a specific indicator of (−)-epicatechin intake, showing also a strong correlation with the amount of (−)-epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92). The median recovery of (−)-epicatechin as SREMB in 24 h urine was 10% (IQR 7–13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 µmol/L. Our results show that SREMB are suitable as biomarker of (−)-epicatechin intake. According to evaluation criteria from IARC and the Institute of Medicine, the results obtained support use of SREMB as a recovery biomarker to estimate actual intake of (−)-epicatechin.
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Affiliation(s)
| | | | | | | | - Nicola Gray
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK
| | | | - Abigail Britten
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | | | - Robert Luben
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | | | | | - Amy Tym
- LGC, Newmarket Road, Fordham, UK
| | | | - A David Smith
- OPTIMA Department of Pharmacology, University of Oxford, Oxford, UK
| | | | - Nita G Forouhi
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | - Kay-Tee Khaw
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | | | - Gunter G C Kuhnle
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK. .,Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
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22
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Lesjak M, K S Srai S. Role of Dietary Flavonoids in Iron Homeostasis. Pharmaceuticals (Basel) 2019; 12:E119. [PMID: 31398897 PMCID: PMC6789581 DOI: 10.3390/ph12030119] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2019] [Revised: 07/29/2019] [Accepted: 08/05/2019] [Indexed: 01/14/2023] Open
Abstract
Balancing systemic iron levels within narrow limits is critical for human health, as both iron deficiency and overload lead to serious disorders. There are no known physiologically controlled pathways to eliminate iron from the body and therefore iron homeostasis is maintained by modifying dietary iron absorption. Several dietary factors, such as flavonoids, are known to greatly affect iron absorption. Recent evidence suggests that flavonoids can affect iron status by regulating expression and activity of proteins involved the systemic regulation of iron metabolism and iron absorption. We provide an overview of the links between different dietary flavonoids and iron homeostasis together with the mechanism of flavonoids effect on iron metabolism. In addition, we also discuss the clinical relevance of state-of-the-art knowledge regarding therapeutic potential that flavonoids may have for conditions that are low in iron such as anaemia or iron overload diseases.
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Affiliation(s)
- Marija Lesjak
- Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
| | - Surjit K S Srai
- Research Department of Structural and Molecular Biology, Division of Biosciences, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
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23
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Ribas-Agustí A, Martín-Belloso O, Soliva-Fortuny R, Elez-Martínez P. Influence of pulsed electric fields processing on the bioaccessible and non-bioaccessible fractions of apple phenolic compounds. J Funct Foods 2019. [DOI: 10.1016/j.jff.2019.05.041] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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24
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Li J, Zeng J, Peng J, Jia Y, Li CM. Simultaneous determination of the pharmacokinetics of A-type EGCG and ECG dimers in mice plasma and its metabolites by UPLC-QTOF-MS. Int J Food Sci Nutr 2019; 71:211-220. [PMID: 31266395 DOI: 10.1080/09637486.2019.1635089] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
A-type epigallocatechin-3-gallate (EGCG) and epicatechin-3-O-gallate (ECG) dimers have multiply biological activities. In this study, the pharmacokinetics of them were investigated in mice after a single dose intravenous administration, and the metabolites in mice plasma and urine were investigated by ultra-performance liquid chromatography-Quadrupole-time of flight mass spectrometer (UPLC-QTOF-MS). Our results showed that the half-life (t1/2) of A-type EGCG and ECG dimers were 116.37 min and 33.04 min, respectively, and the maximal concentration in plasma was 32.81 μg/mL and 55.59 μg/mL, respectively. It was found that two dimers were firstly experienced by quinone methide (QM) fission to form the EGCG and ECG analogue, and the phase II metabolites were generated subsequently. The main metabolites in plasma and urine were glucuronidation and sulphation derivatives. In addition, small molecule weight of phenolic acids were detected in urine.
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Affiliation(s)
- Jin Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Jian Zeng
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Jinming Peng
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Yangyang Jia
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China
| | - Chun-Mei Li
- College of Food Science and Technology, Huazhong Agricultural University, Wuhan, China.,Ministry of Education, Key Laboratory of Environment Correlative Food Science, Huazhong Agricultural University, Wuhan, China
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25
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Ribas-Agustí A, Martín-Belloso O, Soliva-Fortuny R, Elez-Martínez P. Enhancing hydroxycinnamic acids and flavan-3-ol contents by pulsed electric fields without affecting quality attributes of apple. Food Res Int 2019; 121:433-440. [DOI: 10.1016/j.foodres.2018.11.057] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 11/08/2018] [Accepted: 11/26/2018] [Indexed: 12/21/2022]
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26
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Rodriguez-Mateos A, Weber T, Skene SS, Ottaviani JI, Crozier A, Kelm M, Schroeter H, Heiss C. Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial. Am J Clin Nutr 2018; 108:1229-1237. [PMID: 30358831 PMCID: PMC6290365 DOI: 10.1093/ajcn/nqy229] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 08/13/2018] [Indexed: 01/21/2023] Open
Abstract
Background Flavanols are an important class of food bioactives that can improve vascular function even in healthy subjects. Cocoa flavanols (CFs) are composed principally of the monomer (-)-epicatechin (∼20%), with a degree of polymerisation (DP) of 1 (DP1), and oligomeric procyanidins (∼80%, DP2-10). Objective Our objective was to investigate the relative contribution of procyanidins and (-)-epicatechin to CF intake-related improvements in vascular function in healthy volunteers. Design In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 45 healthy men (aged 18-35 y) consumed the following once daily for 1 mo: 1) a DP1-10 cocoa extract containing 130 mg (-)-epicatechin and 560 mg procyanidins, 2) a DP2-10 cocoa extract containing 20 mg (-)-epicatechin and 540 mg procyanidins, or 3) a control capsule, which was flavanol-free but had identical micro- and macronutrient composition. Results Consumption of DP1-10, but not of either DP2-10 or the control capsule, significantly increased flow-mediated vasodilation (primary endpoint) and the concentration of structurally related (-)-epicatechin metabolites (SREMs) in the circulatory system while decreasing pulse wave velocity and blood pressure. Total cholesterol significantly decreased after daily intake of both DP1-10 and DP2-10 as compared with the control. Conclusions CF-related improvements in vascular function are predominantly related to the intake of flavanol monomers and circulating SREMs in healthy humans but not to the more abundant procyanidins and gut microbiome-derived CF catabolites. Reduction in total cholesterol was linked to consumption of procyanidins but not necessarily to that of (-)-epicatechin. This trial was registered at clinicaltrials.gov as NCT02728466.
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Affiliation(s)
- Ana Rodriguez-Mateos
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Dusseldorf, Dusseldorf, Germany
| | - Timon Weber
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Dusseldorf, Dusseldorf, Germany
| | - Simon S Skene
- University of Surrey, Faculty of Health and Medical Sciences, Guildford, United Kingdom
| | | | - Alan Crozier
- Nutrition Department, University of California, Davis, Davis, CA
| | - Malte Kelm
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Dusseldorf, Dusseldorf, Germany
| | | | - Christian Heiss
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Dusseldorf, Dusseldorf, Germany,University of Surrey, Faculty of Health and Medical Sciences, Guildford, United Kingdom,Address correspondence to CH (e-mail: )
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27
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Trans-cinnamaldehyde promotes nitric oxide release via the protein kinase-B/v-Akt murine thymoma viral oncogene -endothelial nitric oxide synthase pathway to alleviate hypertension in SHR. Cg-Leprcp/NDmcr rats. J TRADIT CHIN MED 2018. [DOI: 10.1016/s0254-6272(18)30886-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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28
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Ottaviani JI, Fong R, Kimball J, Ensunsa JL, Britten A, Lucarelli D, Luben R, Grace PB, Mawson DH, Tym A, Wierzbicki A, Khaw KT, Schroeter H, Kuhnle GGC. Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies. Sci Rep 2018; 8:9859. [PMID: 29959422 PMCID: PMC6026136 DOI: 10.1038/s41598-018-28333-w] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2018] [Accepted: 06/21/2018] [Indexed: 12/17/2022] Open
Abstract
The accurate assessment of dietary intake is crucial to investigate the effect of diet on health. Currently used methods, relying on self-reporting and food composition data, are known to have limitations and might not be suitable to estimate the intake of many bioactive food components. An alternative are nutritional biomarkers, which can allow an unbiased assessment of intake. They require a careful evaluation of their suitability, including: (a) the availability of a precise, accurate and robust analytical method, (b) their specificity (c) a consistent relationship with actual intake. We have evaluated human metabolites of a microbiome-derived flavan-3-ol catabolite, 5-(3',4'-dihydroxyphenyl)-[gamma]-valerolactone (gVL), as biomarker of flavan-3-ol intake in large epidemiological studies. Flavan-3-ols are widely consumed plant bioactives, which have received considerable interest due to their potential ability to reduce CVD risk. The availability of authentic standards allowed the development of a validated high-throughput method suitable for large-scale studies. In dietary intervention studies, we could show that gVL metabolites are specific for flavan-3-ols present in tea, fruits, wine and cocoa-derived products, with a strong correlation between intake and biomarker (Spearman's r = 0.90). This biomarker will allow for the first time to estimate flavan-3-ol intake and further investigation of associations between intake and disease risk.
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Affiliation(s)
| | | | | | | | - Abigail Britten
- MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
| | | | - Robert Luben
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | | | | | - Amy Tym
- LGC, Newmarket Road, Fordham, UK
| | | | - Kay-Tee Khaw
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | | | - Gunter G C Kuhnle
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
- Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
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29
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Tsamo AT, Ndibewu PP, Dakora FD. Phytochemical profile of seeds from 21 Bambara groundnut landraces via UPLC-qTOF-MS. Food Res Int 2018; 112:160-168. [PMID: 30131123 DOI: 10.1016/j.foodres.2018.06.028] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Revised: 05/09/2018] [Accepted: 06/13/2018] [Indexed: 11/26/2022]
Abstract
Bambara groundnut is one of the under-utilized African legume crops, valued for its nutritional and health benefits, and for which ongoing studies will help to distinguish its many landraces and select the promising one for breeding programs. To describe the polar metabolome of the seed from 21 Bambara groundnut landraces, untargeted metabolomics approach using UPLC-qTOF-MS (Ultra performance liquid chromatography-Quadrupole time of flight mass spectrometry) was performed. Metabolites belonging to varied compound classes were detected and identified. The total phenolic, flavonoid and anthocyanin contents varied from 0.75 to 17.71 mg GAE.g-1, 0.01 to 2.51 mg QUE.g-1 and 0.03 to 1.31 mg CYE.g-1, respectively. Unsupervised statistics highlighted differences in the metabolome of different landraces. Principal component analysis revealed that caffeic and catechin conjugates are the most decisive marker compounds discriminating the landraces. This study provides the most complete map of metabolites in Bambara groundnut seeds and demonstrates that UPLC-qTOF-MS coupled with chemometric is an excellent tool for differentiation between landraces. These findings highlight the potential of Bambara groundnuts as an economic source of natural antioxidants for human consumption and food industries, and therefore open horizons to the industrial use of Bambara groundnut flours in the development of functional food and feed products.
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Affiliation(s)
- Armelle Tontsa Tsamo
- Department of Chemistry, Tshwane University of Technology, Pretoria 0001, South Africa; Department of Organic Chemistry, University of Yaoundé I, Yaoundé, Cameroon.
| | - Peter Papoh Ndibewu
- Department of Chemistry, Tshwane University of Technology, Pretoria 0001, South Africa
| | - Felix Dapare Dakora
- Department of Chemistry, Tshwane University of Technology, Pretoria 0001, South Africa.
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30
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Ottaviani JI, Heiss C, Spencer JP, Kelm M, Schroeter H. Recommending flavanols and procyanidins for cardiovascular health: Revisited. Mol Aspects Med 2018; 61:63-75. [DOI: 10.1016/j.mam.2018.02.001] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 01/31/2018] [Accepted: 02/06/2018] [Indexed: 12/26/2022]
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31
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Kuhnle GGC. Nutrition epidemiology of flavan-3-ols: The known unknowns. Mol Aspects Med 2017; 61:2-11. [PMID: 29146101 DOI: 10.1016/j.mam.2017.10.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2017] [Revised: 10/19/2017] [Accepted: 10/24/2017] [Indexed: 01/17/2023]
Abstract
Nutritional epidemiology has an important role, as it can provide long-term data from large populations and does not rely on surrogate markers for morbidity/mortality. Meaningful interpretation and applications of outcomes from epidemiological studies depend on the accurate assessment of dietary intake, which is currently mainly based on a combination of self-reporting and food composition data. Flavan-3-ols are a group of bioactives (non-essential dietary components with significant impact on health) that is a possible candidate for the development of dietary recommendations. The breadth of data available on their effect on health also provides the basis for investigating the suitability of the methods currently used in nutritional epidemiology to assess the health effects of bioactives. The outcomes of this assessment demonstrate that the limitations of currently used methods make it virtually impossible to estimate intake accurately from self-reported dietary data. This is due to the limitations of self-reporting, especially from food-frequency questionnaires, and the inability of currently used methods to deal with the high variability of food composition. Indeed, the estimated intake of flavan-3-ols, can only be interpreted as a marker of specific dietary patterns, but not as the actual intake amount. The interpretation of results from such studies are fraught with serious limitations, especially for establishing associations between intake and health and the development of dietary recommendations. Alternative assessment not affected by these limitations, such as biomarkers, are required to overcome these limitations. The development of nutritional biomarkers is therefore crucial to investigate the health effect of bioactives.
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Affiliation(s)
- Gunter G C Kuhnle
- Department of Food & Nutritional Sciences, Harry Nursten Building, University of Reading, Reading RG6 6UR, United Kingdom.
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32
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33
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Vauzour D, Camprubi-Robles M, Miquel-Kergoat S, Andres-Lacueva C, Bánáti D, Barberger-Gateau P, Bowman GL, Caberlotto L, Clarke R, Hogervorst E, Kiliaan AJ, Lucca U, Manach C, Minihane AM, Mitchell ES, Perneczky R, Perry H, Roussel AM, Schuermans J, Sijben J, Spencer JPE, Thuret S, van de Rest O, Vandewoude M, Wesnes K, Williams RJ, Williams RSB, Ramirez M. Nutrition for the ageing brain: Towards evidence for an optimal diet. Ageing Res Rev 2017; 35:222-240. [PMID: 27713095 DOI: 10.1016/j.arr.2016.09.010] [Citation(s) in RCA: 138] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2016] [Revised: 09/05/2016] [Accepted: 09/29/2016] [Indexed: 02/07/2023]
Abstract
As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline.
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Affiliation(s)
- David Vauzour
- University of East Anglia, Norwich Medical School, Norwich NR4 7UQ, United Kingdom
| | - Maria Camprubi-Robles
- Abbott Nutrition R&D, Abbott Laboratories, Camino de Purchil 68, 18004 Granada, Spain
| | | | | | - Diána Bánáti
- International Life Sciences Institute, Europe (ILSI Europe), Av E. Mounier 83, Box 6, 1200 Brussels, Belgium
| | | | - Gene L Bowman
- Nestlé Institute of Health Sciences, EPFL Innovation Park, 1015 Lausanne, Switzerland
| | - Laura Caberlotto
- The Microsoft Research-University of Trento, Centre for Computational and Systems Biology (COSBI), Piazza Manifattura 1, 38068 Rovereto, TN, Italy
| | - Robert Clarke
- Oxford University, Richard Doll Building, Old Road Campus, Roosevelt Drive, OX3 7LF Oxford, United Kingdom
| | - Eef Hogervorst
- Loughborough University, Brockington Building, Asby Road, LE11 3TU Loughborough, United Kingdom
| | - Amanda J Kiliaan
- Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands
| | - Ugo Lucca
- IRCCS-Instituto di Richerche Farmacologiche Mario Negri, Via G. La Masa 19, 20156 Milan, Italy
| | - Claudine Manach
- INRA, UMR 1019, Human Nutrition Unit, CRNH Auvergne, 63000 Clermont-Ferrand, France
| | - Anne-Marie Minihane
- University of East Anglia, Norwich Medical School, Norwich NR4 7UQ, United Kingdom
| | | | - Robert Perneczky
- Imperial College London, South Kensington Campus, SW7 2AZ London, United Kingdom
| | - Hugh Perry
- University of Southampton, Tremona Road, SO16 6YD Southampton, United Kingdom
| | - Anne-Marie Roussel
- Joseph Fourier University, Domaine de la Merci, 38706 La Tronche, France
| | - Jeroen Schuermans
- International Life Sciences Institute, Europe (ILSI Europe), Av E. Mounier 83, Box 6, 1200 Brussels, Belgium.
| | - John Sijben
- Nutricia Research, Nutricia Advances Medical Nutrition, P.O. Box 80141, 3508TC Utrecht, The Netherlands
| | - Jeremy P E Spencer
- University of Reading, Whiteknights, P.O. Box 217, RG6 6AH Reading, Berkshire, United Kingdom
| | - Sandrine Thuret
- King's College London, Institute of Psychiatry, Psychology and Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, 125 Coldharbour Lane, SE5 9NU London, United Kingdom
| | - Ondine van de Rest
- Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands
| | | | - Keith Wesnes
- Wesnes Cognition Ltd., Little Paddock, Streatley on Thames RG8 9RD, United Kingdom; Department of Psychology, Northumbria University, Newcastle, United Kingdom; Centre for Human Psychopharmacology, Swinburne University, Melbourne, Australia; Medicinal Plant Research Group, Newcastle University, United Kingdom
| | | | - Robin S B Williams
- Royal Holloway, University of London, Egham, TW20 0EX Surrey, United Kingdom
| | - Maria Ramirez
- Abbott Nutrition R&D, Abbott Laboratories, Camino de Purchil 68, 18004 Granada, Spain
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Millar CL, Duclos Q, Blesso CN. Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function. Adv Nutr 2017; 8:226-239. [PMID: 28298268 PMCID: PMC5347106 DOI: 10.3945/an.116.014050] [Citation(s) in RCA: 129] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their well-documented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function.
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Fernandes I, Pérez-Gregorio R, Soares S, Mateus N, de Freitas V. Wine Flavonoids in Health and Disease Prevention. Molecules 2017; 22:molecules22020292. [PMID: 28216567 PMCID: PMC6155685 DOI: 10.3390/molecules22020292] [Citation(s) in RCA: 138] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Accepted: 02/10/2017] [Indexed: 02/06/2023] Open
Abstract
Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, soluble proteins, sugars and vitamins. Flavonoids constitute a major group of polyphenolic compounds which are directly associated with the organoleptic and health-promoting properties of red wine. However, due to the insufficient epidemiological and in vivo evidences on this subject, the presence of a high number of variables such as human age, metabolism, the presence of alcohol, the complex wine chemistry, and the wide array of in vivo biological effects of these compounds suggest that only cautious conclusions may be drawn from studies focusing on the direct effect of wine and any specific health issue. Nevertheless, there are several reports on the health protective properties of wine phenolics for several diseases such as cardiovascular diseases, some cancers, obesity, neurodegenerative diseases, diabetes, allergies and osteoporosis. The different interactions that wine flavonoids may have with key biological targets are crucial for some of these health-promoting effects. The interaction between some wine flavonoids and some specific enzymes are one example. The way wine flavonoids may be absorbed and metabolized could interfere with their bioavailability and therefore in their health-promoting effect. Hence, some reports have focused on flavonoids absorption, metabolism, microbiota effect and overall on flavonoids bioavailability. This review summarizes some of these major issues which are directly related to the potential health-promoting effects of wine flavonoids. Reports related to flavonoids and health highlight some relevant scientific information. However, there is still a gap between the knowledge of wine flavonoids bioavailability and their health-promoting effects. More in vivo results as well as studies focused on flavonoid metabolites are still required. Moreover, it is also necessary to better understand how biological interactions (with microbiota and cells, enzymes or general biological systems) could interfere with flavonoid bioavailability.
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Affiliation(s)
- Iva Fernandes
- LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
| | - Rosa Pérez-Gregorio
- LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
| | - Susana Soares
- LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
| | - Nuno Mateus
- LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
| | - Victor de Freitas
- LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.
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Sansone R, Ottaviani JI, Rodriguez-Mateos A, Heinen Y, Noske D, Spencer JP, Crozier A, Merx MW, Kelm M, Schroeter H, Heiss C. Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies. Am J Clin Nutr 2017; 105:352-360. [PMID: 28003203 DOI: 10.3945/ajcn.116.140046] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 11/22/2016] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Cocoa flavanol intake, especially that of (-)-epicatechin, has been linked to beneficial effects on human cardiovascular function. However, cocoa also contains the methylxanthines theobromine and caffeine, which may also affect vascular function. OBJECTIVE We sought to determine whether an interaction between cocoa flavanols and methylxanthines exists that influences cocoa flavanol-dependent vascular effects. DESIGN Test drinks that contained various amounts of cocoa flavanols (0-820 mg) and methylxanthines (0-220 mg), either together or individually, were consumed by healthy volunteers (n = 47) in 4 different clinical studies-3 with a randomized, double-masked crossover design and 1 with 4 parallel crossover studies. Vascular status was assessed by measuring flow-mediated vasodilation (FMD), brachial pulse wave velocity (bPWV), circulating angiogenic cells (CACs), and blood pressure before and 2 h after the ingestion of test drinks. RESULTS Although cocoa flavanol intake increased FMD 2 h after intake, the consumption of cocoa flavanols with methylxanthines resulted in a greater enhancement of FMD. Methylxanthine intake alone did not result in statistically significant changes in FMD. Cocoa flavanol ingestion alone decreased bPWV and diastolic blood pressure and increased CACs. Each of these changes was more pronounced when cocoa flavanols and methylxanthines were ingested together. It is important to note that the area under the curve of the plasma concentration of (-)-epicatechin metabolites over time was higher after the co-ingestion of cocoa flavanols and methylxanthines than after the intake of cocoa flavanols alone. Similar results were obtained when pure (-)-epicatechin and the methylxanthines theobromine and caffeine were consumed together. CONCLUSION A substantial interaction between cocoa flavanols and methylxanthines exists at the level of absorption, in which the methylxanthines mediate an increased plasma concentration of (-)-epicatechin metabolites that coincides with enhanced vascular effects commonly ascribed to cocoa flavanol intake. This trial was registered at clinicaltrials.gov as NCT02149238.
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Affiliation(s)
- Roberto Sansone
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
| | | | - Ana Rodriguez-Mateos
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany.,Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom
| | - Yvonne Heinen
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
| | - Dorina Noske
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
| | - Jeremy P Spencer
- Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, United Kingdom; and
| | - Alan Crozier
- Department of Nutrition, University of California Davis, Davis, CA
| | - Marc W Merx
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
| | - Malte Kelm
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany
| | | | - Christian Heiss
- Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany;
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Abstract
CVD remain the leading cause of death globally. Effective dietary strategies for their reduction are of high priority. Increasing evidence suggests that phytochemicals, particularly dietary flavonoids and nitrates, are key modulators of CVD risk reduction through impact on multiple risk factors. The aim of this review is to explore the evidence for the impact of flavonoid- and nitrate-rich foods and supplements on CVD risk, with specific reference to their importance as mediators of vascular health and platelet function. There is accumulating evidence to support benefits of dietary flavonoids on cardiovascular health. Dose-dependent recovery of endothelial function and lowering of blood pressure have been reported for the flavanol (-)-epicatechin, found in cocoa, apples and tea, through production and availability of endothelial nitric oxide (NO). Furthermore, flavonoids, including quercetin and its metabolites, reduce in vitro and ex vivo platelet function via inhibition of phosphorylation-dependent cellular signalling pathways, although further in vivo studies are required to substantiate these mechanistic effects. Hypotensive effects of dietary nitrates have been consistently reported in healthy subjects in acute and chronic settings, although there is less evidence for these effects in patient groups. Proposed mechanisms of actions include endothelial-independent NO availability, which is dependent on the entro-salivary circulation and microbial conversion of dietary nitrate to nitrite in the mouth. In conclusion, flavonoid- and nitrate-rich foods show promising effects on vascular function, yet further randomly controlled studies are required to confirm these findings and to determine effective doses.
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Affiliation(s)
- Julie A Lovegrove
- Hugh Sinclair Unit of Human Nutrition,Department of Food and Nutritional Sciences,Reading RG6 6AP,UK
| | - Alex Stainer
- Institute for Cardiovascular and Metabolic Research (ICMR),University of Reading,Whiteknights,Reading RG6 6AP,UK
| | - Ditte A Hobbs
- Hugh Sinclair Unit of Human Nutrition,Department of Food and Nutritional Sciences,Reading RG6 6AP,UK
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Aprotosoaie AC, Miron A, Trifan A, Luca VS, Costache II. The Cardiovascular Effects of Cocoa Polyphenols-An Overview. Diseases 2016; 4:E39. [PMID: 28933419 PMCID: PMC5456324 DOI: 10.3390/diseases4040039] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 12/12/2016] [Accepted: 12/13/2016] [Indexed: 12/30/2022] Open
Abstract
Cocoa is a rich source of high-quality antioxidant polyphenols. They comprise mainly catechins (29%-38% of total polyphenols), anthocyanins (4% of total polyphenols) and proanthocyanidins (58%-65% of total polyphenols). A growing body of experimental and epidemiological evidence highlights that the intake of cocoa polyphenols may reduce the risk of cardiovascular events. Beyond antioxidant properties, cocoa polyphenols exert blood pressure lowering activity, antiplatelet, anti-inflammatory, metabolic and anti-atherosclerotic effects, and also improve endothelial function. This paper reviews the role of cocoa polyphenols in cardiovascular protection, with a special focus on mechanisms of action, clinical relevance and correlation between antioxidant activity and cardiovascular health.
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Affiliation(s)
- Ana Clara Aprotosoaie
- Department of Pharmacognosy, Faculty of Pharmacy, University of Medicine and Pharmacy Grigore T. Popa Iasi, Universitatii Str. 16, 700115 Iasi, Romania.
| | - Anca Miron
- Department of Pharmacognosy, Faculty of Pharmacy, University of Medicine and Pharmacy Grigore T. Popa Iasi, Universitatii Str. 16, 700115 Iasi, Romania.
| | - Adriana Trifan
- Department of Pharmacognosy, Faculty of Pharmacy, University of Medicine and Pharmacy Grigore T. Popa Iasi, Universitatii Str. 16, 700115 Iasi, Romania.
| | - Vlad Simon Luca
- Department of Pharmacognosy, Faculty of Pharmacy, University of Medicine and Pharmacy Grigore T. Popa Iasi, Universitatii Str. 16, 700115 Iasi, Romania.
| | - Irina-Iuliana Costache
- Department of Cardiology, Faculty of Medicine, University of Medicine and Pharmacy Grigore T. Popa Iasi, Universitatii Str. 16, 700115 Iasi, Romania.
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Ciocoiu M, Badescu M, Badulescu O, Badescu L. The beneficial effects on blood pressure, dyslipidemia and oxidative stress of Sambucus nigra extract associated with renin inhibitors. PHARMACEUTICAL BIOLOGY 2016; 54:3063-3067. [PMID: 27417664 DOI: 10.1080/13880209.2016.1207088] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 06/16/2016] [Accepted: 06/24/2016] [Indexed: 06/06/2023]
Abstract
CONTEXT The health effects of Sambucus nigra L. (Caprifoliaceae) could be due to polyphenols whose modes of action differ from the traditional one proposed for exogenous antioxidants. OBJECTIVE The study emphasizes the effects of the association between the renin inhibitor and the polyphenolic extract on biochemical parameters and systolic (TAS) and diastolic (TAD) blood pressure within an L NAME-induced experimental model of arterial hypertension (AHT). MATERIALS AND METHODS The polyphenols are extracted with ethanol from isolated and purified vegetable material represented by the mature fruit of the S. nigra with a dosage of 0.046 g/kg body weight (PS), every 2 days, for 8 weeks. The dose represents 1/20 of LD50. The Wistar white rat blood pressure values were recorded using a CODA™ system, which uses a non-invasive blood pressure measuring method. RESULTS AND DISCUSSION The total antioxidant capacity levels were significantly decreased (p < 0.001) in AHT group as compared to the rats in the AHT + PS group. A combination of a renin inhibitor (Aliskiren) and polyphenolic extract generated a superior antioxidant effect compared to administering the two separately. Both TAS and TAD in rats with drug-induced hypertension were reduced by polyphenolic extract. The homogeneous values of TAS record a significant decrease (p < 0.001) of the average values in AHT + PS group or AHT + Aliskiren group. CONCLUSION The combination of two different classes of substances, namely, renin inhibitors and natural polyphenol extracts, reduces arterial pressure and also might reduce the side effects of the major classes of antihypertensive agents and improve the quality of live.
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Affiliation(s)
- Manuela Ciocoiu
- a Department of Pathophysiology, Faculty of Medicine , University of Medicine and Pharmacy 'Grigore T. Popa' Iasi , Romania
| | - Magda Badescu
- a Department of Pathophysiology, Faculty of Medicine , University of Medicine and Pharmacy 'Grigore T. Popa' Iasi , Romania
| | - Oana Badulescu
- a Department of Pathophysiology, Faculty of Medicine , University of Medicine and Pharmacy 'Grigore T. Popa' Iasi , Romania
| | - Laurentiu Badescu
- b Department of Cellular and Molecular Biology , University of Medicine and Pharmacy 'Grigore T. Popa' , Iasi , Romania
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Nunes MA, Pimentel F, Costa AS, Alves RC, Oliveira MBP. Cardioprotective properties of grape seed proanthocyanidins: An update. Trends Food Sci Technol 2016. [DOI: 10.1016/j.tifs.2016.08.017] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
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Borges G, van der Hooft JJJ, Crozier A. A comprehensive evaluation of the [2- 14C](-)-epicatechin metabolome in rats. Free Radic Biol Med 2016; 99:128-138. [PMID: 27495388 DOI: 10.1016/j.freeradbiomed.2016.08.001] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 07/26/2016] [Accepted: 08/01/2016] [Indexed: 12/27/2022]
Abstract
Following ingestion of [2-14C](-)-epicatechin by rats, radioactivity in urine, feces, body fluids and tissues collected over a 72h period, was measured and 14C-metabolites were analyzed by HPLC-MS2 with a radioactivity monitor. In total 78% of the ingested radioactivity was absorbed from the gastrointestinal tract (GIT), and then rapidly eliminated from the circulatory system via renal excretion. A peak plasma concentration occurred 1h after intake corresponding to ~0.7% of intake. Low amounts of radioactivity, <2% of intake, appeared transiently in body tissues. Glucuronidation and methylation of (-)-epicatechin began in the duodenum but occurred more extensively in the jejunum/ileum. Radioactivity reaching the cecum after 6-12h was predominantly in the form of the ring fission metabolites 5-(3',4'-dihydroxyphenyl)-γ-valerolactone and 5-(3',4'-dihydroxyphenyl)-γ-hydroxyvaleric acid along with smaller amounts of their phase II metabolites. Low levels of metabolites were detected in the colon. Of the ingested radioactivity, 19% was voided in feces principally as ring-fission metabolites. The main components in plasma were (-)-epicatechin-5-O-glucuronide and 3'-O-methyl-(-)-epicatechin-5-O-glucuronide with small amounts of (-)-epicatechin, 3'-O-methyl-(-)-epicatechin, 5-(3'-hydroxyphenyl)-γ-hydroxyvaleric acid-4'-glucuronide and hippuric acid also being detected. No oxidized products of (-)-epicatechin were detected. No compelling evidence was obtained for biliary recycling of metabolites. The findings demonstrate substantial differences in the metabolism of (-)-epicatechin by rats and humans. Caution should, therefore, be exercised when using animal models to draw conclusions about effects induced by (-)-epicatechin intake in humans.
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Affiliation(s)
- Gina Borges
- School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK
| | - Justin J J van der Hooft
- School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK
| | - Alan Crozier
- School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Science, University of Glasgow, Glasgow, UK.
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Forte M, Conti V, Damato A, Ambrosio M, Puca AA, Sciarretta S, Frati G, Vecchione C, Carrizzo A. Targeting Nitric Oxide with Natural Derived Compounds as a Therapeutic Strategy in Vascular Diseases. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:7364138. [PMID: 27651855 PMCID: PMC5019908 DOI: 10.1155/2016/7364138] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 07/30/2016] [Accepted: 08/01/2016] [Indexed: 12/20/2022]
Abstract
Within the family of endogenous gasotransmitters, nitric oxide (NO) is the smallest gaseous intercellular messenger involved in the modulation of several processes, such as blood flow and platelet aggregation control, essential to maintain vascular homeostasis. NO is produced by nitric oxide synthases (NOS) and its effects are mediated by cGMP-dependent or cGMP-independent mechanisms. Growing evidence suggests a crosstalk between the NO signaling and the occurrence of oxidative stress in the onset and progression of vascular diseases, such as hypertension, heart failure, ischemia, and stroke. For these reasons, NO is considered as an emerging molecular target for developing therapeutic strategies for cardio- and cerebrovascular pathologies. Several natural derived compounds, such as polyphenols, are now proposed as modulators of NO-mediated pathways. The aim of this review is to highlight the experimental evidence on the involvement of nitric oxide in vascular homeostasis focusing on the therapeutic potential of targeting NO with some natural compounds in patients with vascular diseases.
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Affiliation(s)
- Maurizio Forte
- IRCCS Neuromed, Vascular Physiopathology Unit, Pozzilli, Italy
| | - Valeria Conti
- Università degli Studi di Salerno, Medicine, Surgery and Dentistry, Baronissi, Italy
| | - Antonio Damato
- IRCCS Neuromed, Vascular Physiopathology Unit, Pozzilli, Italy
| | | | - Annibale A. Puca
- Università degli Studi di Salerno, Medicine, Surgery and Dentistry, Baronissi, Italy
- IRCCS Multimedica, Milan, Italy
| | - Sebastiano Sciarretta
- IRCCS Neuromed, Vascular Physiopathology Unit, Pozzilli, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Giacomo Frati
- IRCCS Neuromed, Vascular Physiopathology Unit, Pozzilli, Italy
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy
| | - Carmine Vecchione
- IRCCS Neuromed, Vascular Physiopathology Unit, Pozzilli, Italy
- Università degli Studi di Salerno, Medicine, Surgery and Dentistry, Baronissi, Italy
| | - Albino Carrizzo
- IRCCS Neuromed, Vascular Physiopathology Unit, Pozzilli, Italy
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Ottaviani JI, Borges G, Momma TY, Spencer JPE, Keen CL, Crozier A, Schroeter H. The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives. Sci Rep 2016; 6:29034. [PMID: 27363516 PMCID: PMC4929566 DOI: 10.1038/srep29034] [Citation(s) in RCA: 200] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 06/14/2016] [Indexed: 02/01/2023] Open
Abstract
Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (−)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-14C](−)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations.
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Affiliation(s)
| | - Gina Borges
- Department of Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Tony Y Momma
- Department of Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Jeremy P E Spencer
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AP, UK
| | - Carl L Keen
- Department of Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Alan Crozier
- Department of Nutrition, University of California Davis, Davis, CA 95616, USA
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Prince PD, Lanzi CR, Toblli JE, Elesgaray R, Oteiza PI, Fraga CG, Galleano M. Dietary (-)-epicatechin mitigates oxidative stress, NO metabolism alterations, and inflammation in renal cortex from fructose-fed rats. Free Radic Biol Med 2016; 90:35-46. [PMID: 26569027 DOI: 10.1016/j.freeradbiomed.2015.11.009] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 11/03/2015] [Accepted: 11/08/2015] [Indexed: 12/18/2022]
Abstract
High fructose consumption has been associated to deleterious metabolic conditions. In the kidney, high fructose causes renal alterations that contribute to the development of chronic kidney disease. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate risk factors of chronic diseases. This work investigated the capacity of (-)-epicatechin to prevent the renal damage induced by high fructose consumption in rats. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8 weeks, with or without supplementation with (-)-epicatechin (20mg/kg body weight/d) in the rat chow diet. Results showed that, in the presence of mild proteinuria, the renal cortex from fructose-fed rats exhibited fibrosis and decreases in nephrin, synaptopodin, and WT1, all indicators of podocyte function in association with: (i) increased markers of oxidative stress; (ii) modifications in the determinants of NO bioavailability, i.e., NO synthase (NOS) activity and expression; and (iii) development of a pro-inflammatory condition, manifested as NF-κB activation, and associated with high expression of TNFα, iNOS, and IL-6. Dietary supplementation with (-)-epicatechin prevented or ameliorated the adverse effects of high fructose consumption. These results suggest that (-)-epicatechin ingestion would benefit when renal alterations occur associated with inflammation or metabolic diseases.
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Affiliation(s)
- Paula D Prince
- Physical Chemistry-Institute for Molecular Biochemistry and Molecular Medicine (IBIMOL), School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina
| | - Cecilia Rodríguez Lanzi
- Department of Pathology, School of Medicine, National University of Cuyo, Mendoza, Argentina-Institute of Medicine and Experimental Biology of Cuyo (IMBECU), National Council of Scientific and Technological Research (CONICET), Mendoza, Argentina
| | - Jorge E Toblli
- Laboratory of Experimental Medicine, Hospital Alemán, Buenos Aires, Argentina
| | - Rosana Elesgaray
- Physiology-Institute of Drug Chemistry and Metabolism (IQUIMEFA), School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina
| | - Patricia I Oteiza
- Department of Nutrition, University of California, Davis, CA 95616, USA; Department of Environmental Toxicology, University of California, Davis, CA 95616, USA
| | - César G Fraga
- Physical Chemistry-Institute for Molecular Biochemistry and Molecular Medicine (IBIMOL), School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina; Department of Nutrition, University of California, Davis, CA 95616, USA
| | - Monica Galleano
- Physical Chemistry-Institute for Molecular Biochemistry and Molecular Medicine (IBIMOL), School of Pharmacy and Biochemistry, University of Buenos Aires-National Council of Scientific and Technological Research (CONICET), Buenos Aires, Argentina.
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Ottaviani JI, Balz M, Kimball J, Ensunsa JL, Fong R, Momma TY, Kwik-Uribe C, Schroeter H, Keen CL. Safety and efficacy of cocoa flavanol intake in healthy adults: a randomized, controlled, double-masked trial. Am J Clin Nutr 2015; 102:1425-35. [PMID: 26537937 DOI: 10.3945/ajcn.115.116178] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 09/23/2015] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Evidence from dietary intervention studies shows that the intake of flavanols and procyanidins can be beneficial for cardiovascular health. Nevertheless, there is a clear need for advancing our understanding with regard to safe amounts of intake for these bioactives. OBJECTIVE The aim was to investigate in healthy adults the effects of cocoa flavanol (CF) intake amount and intake duration on blood pressure, platelet function, metabolic variables, and potential adverse events (AEs). DESIGN This investigation consisted of 2 parts. Part 1 was an open-label, intake-amount escalation study, in which 34 healthy adults (aged 35-55 y) consumed escalating amounts of CFs, ranging from 1000 to 2000 mg/d over 6 wk. Primary outcomes were blood pressure and platelet function, select metabolic variables, and the occurrence and severity of AEs. Secondary outcomes included plasma concentrations of CF-derived metabolites and methylxanthines. On the basis of the outcomes of study part 1, and assessing the same outcome measures, part 2 of this investigation was a controlled, randomized, double-masked, 2-parallel-arm dietary intervention study in which healthy participants (aged 35-55 y) were asked to consume for 12 consecutive weeks up to 2000 mg CFs/d (n = 46) or a CF-free control (n = 28). RESULTS Daily intake of up to 2000 mg CFs/d for 12 wk was not associated with significant changes in blood pressure or platelet function compared with CF-free controls in normotensive, healthy individuals who exhibited a very low risk of cardiovascular disease. There were no clinically relevant changes in the metabolic variables assessed in either of the groups. AEs reported were classified as mild in severity and did not significantly differ between study arms. CONCLUSION The consumption of CFs in amounts up to 2000 mg/d for 12 wk was well tolerated in healthy men and women. This trial was registered at clinicaltrials.gov as NCT02447770 (part 1) and NCT02447783 (part 2).
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Affiliation(s)
| | | | | | | | | | | | | | | | - Carl L Keen
- Nutrition and Internal Medicine, University of California, Davis, Davis, CA
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46
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Ge ZZ, Dong XQ, Zhu W, Zhang Y, Li CM. Metabolites and Changes in Antioxidant Activity of A-Type and B-Type Proanthocyanidin Dimers after Incubation with Rat Intestinal Microbiota. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2015; 63:8991-8998. [PMID: 26420512 DOI: 10.1021/acs.jafc.5b03657] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Metabolism of B-type EC dimer, A-type EC dimer, A-type ECG dimer, and A-type EGCG dimer was compared in vitro after incubation with rat intestinal microbiota for 0-24 h. A "dimeric" catabolite (m/z 815.6) was detected in four procyanthocyanidin dimers. Although the early cleavage of the C4-C8 interflavan bond and the reductive cleavage of the C-ring occurred in both B-type and A-type dimers, the degradation routes of these two types of dimers might somewhat differ. A dimeric catabolite C1 and more low molecular weight phenolic acids were detected in the metabolites of A-type EC dimer, but not in B-type EC dimer. The antioxidant capabilities of the A-type dimers were enhanced significantly after incubation for 6 h, whereas the antioxidant capacity of B-type EC dimer decreased. The results suggested that changes in antioxidant activity of procyanidin dimers after bioconversion by rat intestinal microbiota were not only structure dependent but also incubation condition dependent.
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Affiliation(s)
- Zhen-zhen Ge
- College of Food Science and Technology, Huazhong Agricultural University , Wuhan, China 430070
| | - Xiao-qian Dong
- College of Food Science and Technology, Huazhong Agricultural University , Wuhan, China 430070
| | - Wei Zhu
- College of Food Science and Technology, Huazhong Agricultural University , Wuhan, China 430070
| | - Ying Zhang
- College of Food Science and Technology, Huazhong Agricultural University , Wuhan, China 430070
| | - Chun-mei Li
- College of Food Science and Technology, Huazhong Agricultural University , Wuhan, China 430070
- Key Laboratory of Environment Correlative Food Science (Huazhong Agricultural University), Ministry of Education , Wuhan, China 430070
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Li S, Xu M, Niu Q, Xu S, Ding Y, Yan Y, Guo S, Li F. Efficacy of Procyanidins against In Vivo Cellular Oxidative Damage: A Systematic Review and Meta-Analysis. PLoS One 2015; 10:e0139455. [PMID: 26426531 PMCID: PMC4591260 DOI: 10.1371/journal.pone.0139455] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 09/14/2015] [Indexed: 01/18/2023] Open
Abstract
AIMS In this study, the efficacy of proanthocyanidins (PCs) against oxidative damage was systematically reviewed to facilitate their use in various applications. METHODS A meta-analysis was performed by two researchers. Each investigator independently searched electronic databases, including Cochrane, PubMed, Springer, Web of Science, China National Knowledge Infrastructure (CKNI), China Science and Technology Journal Database (CSTJ), and WanFang Data, and analyzed published data from 29 studies on the effects of PCs against oxidative damage. Oxidative stress indexes included superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and total antioxidative capacity (T-AOC). RESULTS Compared with the oxidative damage model group, PCs effectively improved the T-AOC, SOD, GSH, GPx, and CAT levels, and reduced the MDA levels; these differences were statistically significant (P < 0.05). In studies that used the gavage method, SOD (95% CI, 2.33-4.00) and GPx (95% CI, 2.10-4.05) were 3.16-fold and 3.08-fold higher in the PC group than in the control group, respectively. In studies that used the feeding method, SOD (95% CI, 0.32-1.74) and GPx (95% CI, -0.31 to 1.65) were 1.03-fold and 0.67-fold higher in the PC group than in the control group, respectively. Statistically significant differences in the effects of PCs (P < 0.00001) were observed between these two methods. MDA estimated from tissue samples (95% CI, -5.82 to -2.60) was 4.32-fold lower in the PC group than in the control group. In contrast, MDA estimated using serum samples (95% CI, -4.07 to -2.06) was 3.06-fold lower in the PC group than in the control group. The effect of PCs on MDA was significantly greater in tissue samples than in serum samples (P = 0.02). CONCLUSION PCs effectively antagonize oxidative damage and enhance antioxidant capacity. The antagonistic effect may be related to intervention time, intervention method, and the source from which the indexes are estimated.
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Affiliation(s)
- Shugang Li
- Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, China
| | - Mengchuan Xu
- Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, China
| | - Qiang Niu
- Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, China
| | - Shangzhi Xu
- Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, China
| | - Yusong Ding
- Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, China
| | - Yizhong Yan
- Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, China
| | - Shuxia Guo
- Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Xinjiang, China
| | - Feng Li
- Department of Pathology and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, China
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Primetta AK, Karppinen K, Riihinen KR, Jaakola L. Metabolic and molecular analyses of white mutant Vaccinium berries show down-regulation of MYBPA1-type R2R3 MYB regulatory factor. PLANTA 2015; 242:631-43. [PMID: 26168981 DOI: 10.1007/s00425-015-2363-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 06/30/2015] [Indexed: 05/06/2023]
Abstract
MYBPA1-type R2R3 MYB transcription factor shows down-regulation in white mutant berries of Vaccinium uliginosum deficient in anthocyanins but not proanthocyanidins suggesting a role in the regulation of anthocyanin biosynthesis. Berries of the genus Vaccinium are among the best natural sources of flavonoids. In this study, the expression of structural and regulatory flavonoid biosynthetic genes and the accumulation of flavonoids in white mutant and blue-colored wild-type bog bilberry (V. uliginosum) fruits were measured at different stages of berry development. In contrast to high contents of anthocyanins in ripe blue-colored berries, only traces were detected by HPLC-ESI-MS in ripe white mutant berries. However, similar profile and high levels of flavonol glycosides and proanthocyanidins were quantified in both ripe white and ripe wild-type berries. Analysis with qRT-PCR showed strong down-regulation of structural genes chalcone synthase (VuCHS), dihydroflavonol 4-reductase (VuDFR) and anthocyanidin synthase (VuANS) as well as MYBPA1-type transcription factor VuMYBPA1 in white berries during ripening compared to wild-type berries. The profiles of transcript accumulation of chalcone isomerase (VuCHI), anthocyanidin reductase (VuANR), leucoanthocyanidin reductase (VuLAR) and flavonoid 3'5' hydroxylase (VuF3'5'H) were more similar between the white and the wild-type berries during fruit development, while expression of UDP-glucose: flavonoid 3-O-glucosyltransferase (VuUFGT) showed similar trend but fourfold lower level in white mutant. VuMYBPA1, the R2R3 MYB family member, is a homologue of VmMYB2 of V. myrtillus and VcMYBPA1 of V. corymbosum and belongs to MYBPA1-type MYB family which members are shown in some species to be related with proanthocyanidin biosynthesis in fruits. Our results combined with earlier data of the role of VmMYB2 in white mutant berries of V. myrtillus suggest that the regulation of anthocyanin biosynthesis in Vaccinium species could differ from other species studied.
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Affiliation(s)
- Anja K Primetta
- Department of Environmental Science, University of Eastern Finland, P.O. Box 1627, 70211, Kuopio, Finland
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The mechanisms of action of flavonoids in the brain: Direct versus indirect effects. Neurochem Int 2015; 89:126-39. [PMID: 26260546 DOI: 10.1016/j.neuint.2015.08.002] [Citation(s) in RCA: 117] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Revised: 08/04/2015] [Accepted: 08/05/2015] [Indexed: 02/01/2023]
Abstract
The projected increase in the incidence of dementia in the population highlights the urgent need for a more comprehensive understanding of how different aspects of lifestyle, in particular exercise and diet, may affect neural function and consequent cognitive performance throughout the life course. In this regard, flavonoids, found in a variety of fruits, vegetables and derived beverages, have been identified as a group of promising bioactive compounds capable of influencing different aspects of brain function, including cerebrovascular blood flow and synaptic plasticity, both resulting in improvements in learning and memory in mammalian species. However, the precise mechanisms by which flavonoids exert these actions are yet to be fully established, although accumulating data indicate an ability to interact with neuronal receptors and kinase signaling pathways which are key to neuronal activation and communication and synaptic strengthening. Alternatively or concurrently, there is also compelling evidence derived from human clinical studies suggesting that flavonoids can positively affect peripheral and cerebrovascular blood flow, which may be an indirect effective mechanism by which dietary flavonoids can impact on brain health and cognition. The current review examines the beneficial effects of flavonoids on both human and animal brain function and attempts to address and link direct and indirect actions of flavonoids and their derivatives within the central nervous system (CNS).
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