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Maxones A, Beck E, Rimbach G, Birringer M. A New LC-MS/MS-Based Method for the Simultaneous Detection of α-Tocopherol and Its Long-Chain Metabolites in Plasma Samples Using Stable Isotope Dilution Analysis. Pharmaceuticals (Basel) 2024; 17:1405. [PMID: 39598322 PMCID: PMC11597593 DOI: 10.3390/ph17111405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/10/2024] [Accepted: 10/19/2024] [Indexed: 11/29/2024] Open
Abstract
Background: Our study presented a novel LC-MS/MS method for the simultaneous quantification of α-tocopherol (α-TOH) and its phase II metabolites, α-13'-COOH and α-13'-OH, in human serum using deuterium-labeled internal standards (d6-α-TOH, d6-α-13'-COOH, d6-α-13'-OH). Methods: The method addresses the analytical challenge posed by the significantly different concentration ranges of α-TOH (µmol/L) and its metabolites (nmol/L). Previous methods quantified these analytes separately, which caused an increase in workflow complexity. Results: Key features include the synthesis of stable isotope-labeled standards and the use of a pentafluorophenyl-based core-shell chromatography column for baseline separation of both α-TOH and its metabolites. Additionally, solid phase extraction (SPE) with a HybridSPE® material provides a streamlined sample preparation, enhancing analyte recovery and improving sensitivity. By utilizing deuterium-labeled standards, the method compensates for matrix effects and ion suppression. This new approach achieves precise and accurate measurements with limits of detection (LOD) and quantification (LOQ), similar to previous studies. Calibration, accuracy, and precision parameters align well with the existing literature. Conclusions: Our method offers significant advantages in the simultaneous analysis of tocopherol and its metabolites despite concentration differences spanning up to three orders of magnitude. In contrast to earlier studies, which required separate sample preparations and analytical techniques for tocopherol and its metabolites, our approach streamlines this process. The use of a solid-phase extraction procedure allows for parallel sample preparation. This not only enhances efficiency but also significantly accelerates pre-analytical workflows, making the method highly suitable for large-scale studies.
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Affiliation(s)
- Alexander Maxones
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, 36037 Fulda, Germany; (A.M.); (E.B.)
- Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany;
| | - Eva Beck
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, 36037 Fulda, Germany; (A.M.); (E.B.)
- Food Chemistry, Department of Chemistry and Pharmacy, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91058 Erlangen, Germany
| | - Gerald Rimbach
- Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany;
| | - Marc Birringer
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, 36037 Fulda, Germany; (A.M.); (E.B.)
- Public Health Zentrum Fulda (PHZF), Fulda University of Applied Sciences, 36037 Fulda, Germany
- Wissenschaftliches Zentrum für Ernährung, Lebensmittel und Nachhaltige Versorgungssysteme (ELVe), Fulda University of Applied Sciences, 36037 Fulda, Germany
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Listyoko AS, Okazaki R, Harada T, Takata M, Morita M, Ishikawa H, Funaki Y, Yamasaki A. β-Tocotrienol Decreases PDGF-BB-Induced Proliferation and Migration of Human Airway Smooth Muscle Cells by Inhibiting RhoA and Reducing ROS Production. Pharmaceuticals (Basel) 2024; 17:712. [PMID: 38931379 PMCID: PMC11206512 DOI: 10.3390/ph17060712] [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: 03/18/2024] [Revised: 04/12/2024] [Accepted: 05/28/2024] [Indexed: 06/28/2024] Open
Abstract
BACKGROUND Tocotrienols exhibit antioxidant and anti-inflammatory activities. RhoA, a small GTPase protein, plays a crucial role in regulating contractility in airway smooth muscle (ASM). Previous studies have demonstrated that γ-tocotrienols reduce ASM proliferation and migration by inhibiting the activation of RhoA. In this present study, we investigate the effect of another vitamin E isoform, β-tocotrienols, on human ASM cell proliferation and migration stimulated by platelet-derived growth factor-BB (PDGF-BB). METHODS Human ASM cells were pre-treated with β-tocotrienol prior to being stimulated with PDGF-BB to induce ASM cell proliferation and migration. The proliferation and migration of PDGF-BB-induced human ASM cells were assessed using colorimetric and transwell migration assays. The intracellular ROS assay kit was employed to quantify reactive oxygen species (ROS) in human ASM cells. Additionally, we explored the effect of β-tocotrienols on the signaling pathways involved in PDGF-BB-induced ASM proliferation and migration. RESULTS β-tocotrienol inhibited PDGF-BB-induced ASM cell proliferation and migration by reducing RhoA activation and ROS production. However, in this present study, β-tocotrienol did not affect the signaling pathways associated with cyclin D1, phosphorylated Akt1, and ERK1/2. CONCLUSIONS In conclusion, the inhibition of RhoA activation and ROS production by β-tocotrienol, resulting in the reduction in human ASM proliferation and migration, suggests its potential as a treatment for asthma airway remodeling.
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Affiliation(s)
- Aditya Sri Listyoko
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan; (R.O.); (T.H.); (M.T.); (M.M.); (H.I.); (Y.F.)
| | | | | | | | | | | | | | - Akira Yamasaki
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago 683-8504, Japan; (R.O.); (T.H.); (M.T.); (M.M.); (H.I.); (Y.F.)
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Razem M, Morozova K, Ding Y, Ferrentino G, Scampicchio M. Determination of free and bound antioxidants in Kamut® wheat by HPLC with triple detector (DAD-CAD-MS). Food Chem X 2024; 21:101216. [PMID: 38384689 PMCID: PMC10879663 DOI: 10.1016/j.fochx.2024.101216] [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] [Received: 09/13/2023] [Revised: 02/06/2024] [Accepted: 02/08/2024] [Indexed: 02/23/2024] Open
Abstract
Kamut® wheat (Triticum turgidum ssp. turanicum), an ancient, underutilized cereal, offers potential health benefits due to its phenolic compounds. This study aimed to investigate the antioxidant potential of Kamut® wheat's free and bound phenolic extracts using an HPLC system equipped with three detectors. The bound extracts, released after alkaline hydrolysis, exhibited higher total phenolic and flavonoid content compared to the free extracts (p < 0.05). The total antioxidant capacity of bound extracts was six-fold greater than in free extracts (p < 0.05). The main antioxidants in free extracts were tyrosine, phenylalanine, tryptophan, and apigenin. In bound extracts, ferulic acid, its dimers and trimer were present. Kamut® wheat exhibited a source of dietary antioxidants and should be considered a potential ingredient for the development of functional foods. Also, the HPLC-triple detector system is effective for in-depth profiling of antioxidant compounds, paving the way for future research on similar grains.
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Affiliation(s)
- Mutasem Razem
- Faculty of Agricultural, Environmental and Food Sciences, Free University of Bozen-Bolzano, Piazza Università 1, 39100 Bolzano, Italy
| | - Ksenia Morozova
- Faculty of Agricultural, Environmental and Food Sciences, Free University of Bozen-Bolzano, Piazza Università 1, 39100 Bolzano, Italy
| | - Yubin Ding
- Faculty of Agricultural, Environmental and Food Sciences, Free University of Bozen-Bolzano, Piazza Università 1, 39100 Bolzano, Italy
| | - Giovanna Ferrentino
- Faculty of Agricultural, Environmental and Food Sciences, Free University of Bozen-Bolzano, Piazza Università 1, 39100 Bolzano, Italy
| | - Matteo Scampicchio
- Faculty of Agricultural, Environmental and Food Sciences, Free University of Bozen-Bolzano, Piazza Università 1, 39100 Bolzano, Italy
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El-Banna AA, Ibrahim RS. Metabolic profiling of milk thistle different organs using UPLC-TQD-MS/MS coupled to multivariate analysis in relation to their selective antiviral potential. BMC Complement Med Ther 2024; 24:115. [PMID: 38454377 PMCID: PMC10921647 DOI: 10.1186/s12906-024-04411-7] [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: 09/09/2023] [Accepted: 02/26/2024] [Indexed: 03/09/2024] Open
Abstract
INTRODUCTION Silybum marianum commonly known as milk thistle is one of the most imperative medicinal plants due to its remarkable pharmacological activities. Lately, the antiviral activities of S. marianum extract have been studied and it showed effectiveness against many viruses. OBJECTIVE Although most previous studies were concerned mainly with silymarin content of the fruit, the present study provides comprehensive comparative evaluation of S. marianum different organs' chemical profiles using UPLC-MS/MS coupled to chemometrics to unravel potentially selective antiviral compounds against human coronavirus (HCoV-229E). METHODOLOGY UPLC-ESI-TQD-MS/MS analysis was utilized to establish metabolic fingerprints for S. marianum organs namely fruits, roots, stems and seeds. Multivariate analysis, using OPLS-DA and HCA-heat map was applied to explore the main discriminatory phytoconstituents between organs. Selective virucidal activity of organs extracts against coronavirus (HCoV-229E) was evaluated for the first time using cytopathic effect (CPE) inhibition assay. Correlation coefficient analysis was implemented for detection of potential constituents having virucidal activity. RESULTS UPLC-MS/MS analysis resulted in 87 identified metabolites belonging to different classes. OPLS-DA revealed in-between class discrimination between milk thistle organs proving their significantly different metabolic profiles. The results of CPE assay showed that all tested organ samples exhibited dose dependent inhibitory activity in nanomolar range. Correlation analysis disclosed that caffeic acid-O-hexoside, gadoleic and linolenic acids were the most potentially selective antiviral phytoconstituents. CONCLUSION This study valorizes the importance of different S. marianum organs as wealthy sources of selective and effective antiviral candidates. This approach can be extended to unravel potentially active constituents from complex plant matrices.
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Affiliation(s)
- Alaa A El-Banna
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Reham S Ibrahim
- Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
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Traber MG. Human Vitamin E deficiency, and what is and is not Vitamin E? Free Radic Biol Med 2024; 213:285-292. [PMID: 38242248 PMCID: PMC10923111 DOI: 10.1016/j.freeradbiomed.2024.01.024] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/04/2024] [Accepted: 01/16/2024] [Indexed: 01/21/2024]
Affiliation(s)
- Maret G Traber
- Linus Pauling Institute, Oregon State University, Corvallis, OR, 97331, USA
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Matthew KA, Getz KR, Jeon MS, Luo C, Luo J, Toriola AT. Associations of Vitamins and Related Cofactor Metabolites with Mammographic Breast Density in Premenopausal Women. J Nutr 2024; 154:424-434. [PMID: 38122846 PMCID: PMC10900193 DOI: 10.1016/j.tjnut.2023.12.023] [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: 09/18/2023] [Revised: 12/12/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023] Open
Abstract
BACKGROUND Identifying biological drivers of mammographic breast density (MBD), a strong risk factor for breast cancer, could provide insight into breast cancer etiology and prevention. Studies on dietary factors and MBD have yielded conflicting results. There are, however, very limited data on the associations of dietary biomarkers and MBD. OBJECTIVE We aimed to investigate the associations of vitamins and related cofactor metabolites with MBD in premenopausal women. METHODS We measured 37 vitamins and related cofactor metabolites in fasting plasma samples of 705 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. Volpara was used to assess volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). We estimated the least square means of VPD, DV, and NDV across quartiles of each metabolite, as well as the regression coefficient of a metabolite in continuous scale from multiple covariate-adjusted linear regression. We corrected for multiple testing using the Benjamini-Hochberg procedure to control the false discover rate (FDR) at a 5% level. RESULTS Participants' mean VPD was 10.5%. Two vitamin A metabolites (β-cryptoxanthin and carotene diol 2) were positively associated, and one vitamin E metabolite (γ-tocopherol) was inversely associated with VPD. The mean VPD increased across quartiles of β-cryptoxanthin (Q1 = 7.2%, Q2 = 7.7%, Q3 = 8.4%%, Q4 = 9.2%; P-trend = 1.77E-05, FDR P value = 1.18E-03). There was a decrease in the mean VPD across quartiles of γ-tocopherol (Q1 = 9.4%, Q2 = 8.1%, Q3 = 8.0%, Q4 = 7.8%; P -trend = 4.01E-03, FDR P value = 0.04). Seven metabolites were associated with NDV: 3 vitamin E (γ-CEHC glucuronide, δ-CEHC, and γ-tocopherol) and 1 vitamin C (gulonate) were positively associated, whereas 2 vitamin A (carotene diol 2 and β-cryptoxanthin) and 1 vitamin C (threonate) were inversely associated with NDV. No metabolite was significantly associated with DV. CONCLUSION We report novel associations of vitamins and related cofactor metabolites with MBD in premenopausal women.
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Affiliation(s)
- Kayode A Matthew
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
| | - Kayla R Getz
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
| | - Myung Sik Jeon
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States; Siteman Cancer Center Biostatistics and Qualitative Research Shared Resource, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
| | - Chongliang Luo
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States; Siteman Cancer Center Biostatistics and Qualitative Research Shared Resource, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
| | - Jingqin Luo
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States; Siteman Cancer Center Biostatistics and Qualitative Research Shared Resource, Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States
| | - Adetunji T Toriola
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, United States; Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, United States.
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Pawlak K, Jopek Z, Święcicka-Füchsel E, Kutyła A, Namo Ombugadu J, Wojciechowski K. A new RPLC-ESI-MS method for the determination of eight vitamers of vitamin E. Food Chem 2024; 432:137161. [PMID: 37633151 DOI: 10.1016/j.foodchem.2023.137161] [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: 05/14/2023] [Revised: 08/04/2023] [Accepted: 08/13/2023] [Indexed: 08/28/2023]
Abstract
Vitamin E consists of four (α-, β-, γ-, δ-) isoforms of tocopherols (T) and tocotrienols (T3), collectively known as tocols. Current LC methods for tocols suffer from either the poor ability to resolve the β- and γ- isoforms (RPLC), or require the use of nonpolar solvents (NPLC), which complicates subsequent MS/MS detection. Moreover, we show that coupling of UV with MS leads to tocols photodegradation. To solve these problems, we developed a new RPLC-MS/MS method, allowing to resolve not only α- and δ-, but also β- and γ- tocols in hydrophobic matrices. We took advantage of an observation that the peak area ratios are specific for the given isomer and constant. The new method with a linear range between 0.2 and 60 ng·mL-1 (for α-T) and 1.1-60 ng·mL-1 (for β-T3 and γ-T3) was validated and employed for quantitative analysis of several oils, including false flax (Camelina sativa) oil stored under different conditions.
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Affiliation(s)
- Katarzyna Pawlak
- Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland.
| | - Zuzanna Jopek
- Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland
| | | | - Alicja Kutyła
- Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland
| | | | - Kamil Wojciechowski
- Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland; Department of Chemistry, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland.
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de Sousa Coelho MDPS, Pereira IC, de Oliveira KGF, Oliveira IKF, Dos Santos Rizzo M, de Oliveira VA, Carneiro da Silva FC, Torres-Leal FL, de Castro E Sousa JM. Chemopreventive and anti-tumor potential of vitamin E in preclinical breast cancer studies: A systematic review. Clin Nutr ESPEN 2023; 53:60-73. [PMID: 36657931 DOI: 10.1016/j.clnesp.2022.11.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 10/17/2022] [Accepted: 11/02/2022] [Indexed: 11/06/2022]
Abstract
BACKGROUND Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity. OBJECTIVE Therefore, this systematic review aimed to evaluate antitumor and chemopreventive activity of different vitamin E isoforms (tocopherols and tocotrienols) through in vitro and in vivo studies. METHOD The systematic review was registered in PROSPERO (No. CRD4202126207) and the search was carried out in four electronic databases (PubMed, Science Direct, Scopus and Web of Science) in June 2021 by three independent reviewers. The search equation used was: "Supplementation" AND ("Vitamin E" OR Tocopherol OR Tocotrienol) AND "breast cancer" AND (chemotherapy OR therapy OR prevention). In vitro studies and animal models of breast cancer supplemented with tocopherol or tocotrienol vitamers, alone or in combination, were included. RESULTS The results revealed 8546 relevant studies that were initially identified in our search. After analysis, a total of 12 studies were eligible for this systematic review. All studies included animal models, and 5 of them also performed in vitro experiments on cancer cell lines. The studies performed supplementation with tocopherols, mixtures (tocopherols and tocotrienols) and synthetic vitamin E forms. There was an significant association of estradiol, dendritic cells and pterostilbene in combined therapy with vitamin E. Vitamin E delayed tumor development, reduced tumor size, proliferation, viability, expression of anti-apoptotic and cell proliferation genes, and upregulated pro-apoptotic genes, tumor suppressor genes and increased immune response. The effects on oxidative stress markers and antioxidant activity were conflicting among studies. Only one study with synthetic vitamin E reported cardiotoxicity, but it did not show vitamin E genotoxicity. CONCLUSION In conclusion, vitamin E isoforms, isolated or associated, showed antitumor and chemopreventive activity. However, due to studies heterogeneity, there is a need for further analysis to establish dose, form, supplementation time and breast cancer stage.
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Affiliation(s)
- Maria do Perpetuo Socorro de Sousa Coelho
- Laboratory of Genetical Toxicology (LAPGENIC), Center for Health Sciences, Graduate Program in Pharmaceutical Sciences - Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Irislene Costa Pereira
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina, Piauí, Brazil
| | - Kynnara Gabriella Feitosa de Oliveira
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina, Piauí, Brazil
| | - Iara Katryne Fonseca Oliveira
- Department of Nutrition, Postgraduate Program in Food and Nutrition - PPGAN, Federal University of Piauí, Teresina, Piauí, Brazil
| | - Márcia Dos Santos Rizzo
- Department of Morphology, Health Sciences Center, Federal University of Piaui, Teresina, Piauí, Brazil
| | - Victor Alves de Oliveira
- Department of Nutrition, Postgraduate Program in Food and Nutrition - PPGAN, Federal University of Piauí, Teresina, Piauí, Brazil
| | | | - Francisco Leonardo Torres-Leal
- Metabolic Diseases, Exercise and Nutrition Research Group (DOMEN), Department of Biophysics and Physiology, Center for Health Sciences, Federal University of Piaui, Teresina, Piauí, Brazil
| | - João Marcelo de Castro E Sousa
- Laboratory of Genetical Toxicology (LAPGENIC), Center for Health Sciences, Graduate Program in Pharmaceutical Sciences - Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, Brazil.
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Borel P, Dangles O, Kopec RE. Fat-soluble vitamin and phytochemical metabolites: Production, gastrointestinal absorption, and health effects. Prog Lipid Res 2023; 90:101220. [PMID: 36657621 DOI: 10.1016/j.plipres.2023.101220] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 12/12/2022] [Accepted: 01/12/2023] [Indexed: 01/18/2023]
Abstract
Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phytochemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon. This review compiles the known metabolites of fat-soluble vitamins and fat-soluble phytochemicals (FSV and FSP) that have been identified in food and in the human digestive tract, or could potentially be present based on the known reactivity of the parent compounds in normal or pathological conditions, or following surgical interventions of the digestive tract or consumption of xenobiotics known to impair lipid absorption. It also covers the very limited data available on the bioavailability (absorption, intestinal mucosa metabolism) and summarizes their effects on health. Notably, despite great interest in identifying bioactive derivatives of FSV and FSP, studying their absorption, and probing their putative health effects, much research remains to be conducted to understand and capitalize on the potential of these molecules to preserve health.
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Affiliation(s)
- Patrick Borel
- C2VN, INRAE, INSERM, Aix-Marseille Univ, Marseille, France.
| | | | - Rachel E Kopec
- Human Nutrition Program, Department of Human Sciences, Foods for Health Discovery Theme, The Ohio State University, Columbus, OH 43210, USA.
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Fernando IPS, Fernando PWP, Kim T, Ahn G. Structural diversity, biosynthesis, and health-promoting properties of brown algal meroditerpenoids. Crit Rev Biotechnol 2022; 42:1238-1259. [PMID: 34875939 DOI: 10.1080/07388551.2021.2001639] [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: 03/29/2021] [Revised: 08/09/2021] [Accepted: 09/08/2021] [Indexed: 10/19/2022]
Abstract
Marine algae that constitute hundreds of millions of tons of biomass are the oldest representatives of the plant kingdom. Recently, there has been growing interest in the utilization of algae as sustainable feedstocks for natural products with an economic value. Among these natural products are the meroditerpenoids, which are renowned for their protective effects against oxidative stress, inflammation, cancer, obesity, diabetes, and neurodegenerative disorders. Meroditerpenoids have a mixed biosynthetic origin and display a wide range of structural diversity. Their basic structure consists of a ring system bearing a diterpenoid side chain. Structural variations are observed in terms of the functional groups and saturation/cyclization of the diterpenoid side chain. This review classifies algal meroditerpenoids as plastoquinones, chromanols, chromenes, chromones, cyclic meroditerpenoids, nahocols, and isonahocols and examines their potential applications in functional foods and biopharmacology. Their lipid solubility, low molecular weight, and propensity to cross the blood-brain barrier places meroditerpenoids as potential drug candidates. There is growing interest in the study of algal meroterpenoids, and recent research has reported the structure of several new meroterpenoids and their biological activities. Further research is needed to extend the use of algal meroditerpenoids in preclinical trials. Understanding the mechanism of their biosynthesis will allow the development of de novo biosynthesis and biomimetic synthesis strategies for the industrial-scale production of meroditerpenoids and their synthetic derivatives to aid pharmaceutical research. This review is the first to summarize up-to-date information on all brown algae-derived meroditerpenoids.
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Affiliation(s)
| | | | - Taeho Kim
- Division of Marine Technology, Chonnam National University, Yeosu, South Korea
| | - Ginnae Ahn
- Department of Marine Bio-Food Sciences, Chonnam National University, Yeosu, South Korea
- Department of Food Technology and Nutrition, Chonnam National University, Yeosu, South Korea
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11
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Chen L, Zhernakova DV, Kurilshikov A, Andreu-Sánchez S, Wang D, Augustijn HE, Vich Vila A, Weersma RK, Medema MH, Netea MG, Kuipers F, Wijmenga C, Zhernakova A, Fu J. Influence of the microbiome, diet and genetics on inter-individual variation in the human plasma metabolome. Nat Med 2022; 28:2333-2343. [PMID: 36216932 PMCID: PMC9671809 DOI: 10.1038/s41591-022-02014-8] [Citation(s) in RCA: 134] [Impact Index Per Article: 44.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 08/15/2022] [Indexed: 01/14/2023]
Abstract
The levels of the thousands of metabolites in the human plasma metabolome are strongly influenced by an individual's genetics and the composition of their diet and gut microbiome. Here, by assessing 1,183 plasma metabolites in 1,368 extensively phenotyped individuals from the Lifelines DEEP and Genome of the Netherlands cohorts, we quantified the proportion of inter-individual variation in the plasma metabolome explained by different factors, characterizing 610, 85 and 38 metabolites as dominantly associated with diet, the gut microbiome and genetics, respectively. Moreover, a diet quality score derived from metabolite levels was significantly associated with diet quality, as assessed by a detailed food frequency questionnaire. Through Mendelian randomization and mediation analyses, we revealed putative causal relationships between diet, the gut microbiome and metabolites. For example, Mendelian randomization analyses support a potential causal effect of Eubacterium rectale in decreasing plasma levels of hydrogen sulfite-a toxin that affects cardiovascular function. Lastly, based on analysis of the plasma metabolome of 311 individuals at two time points separated by 4 years, we observed a positive correlation between the stability of metabolite levels and the amount of variance in the levels of that metabolite that could be explained in our analysis. Altogether, characterization of factors that explain inter-individual variation in the plasma metabolome can help design approaches for modulating diet or the gut microbiome to shape a healthy metabolome.
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Affiliation(s)
- Lianmin Chen
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Cardiology, Nanjing Medical University, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Cardiovascular Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Daria V Zhernakova
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Laboratory of Genomic Diversity, Center for Computer Technologies, ITMO University, St. Petersburg, Russia
| | - Alexander Kurilshikov
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Sergio Andreu-Sánchez
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Daoming Wang
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Hannah E Augustijn
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Bioinformatics Group, Wageningen University, Wageningen, the Netherlands
| | - Arnau Vich Vila
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Marnix H Medema
- Bioinformatics Group, Wageningen University, Wageningen, the Netherlands
| | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany
| | - Folkert Kuipers
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
- European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Cisca Wijmenga
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Alexandra Zhernakova
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jingyuan Fu
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
- Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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12
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Khallouki F, Saber S, Bouddine T, Hajji L, Elbouhali B, Silvente-Poirot S, Poirot M. In vitro and In vivo oxidation and cleavage products of tocols: From chemical tuners to “VitaminEome” therapeutics. A narrative review. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.101839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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Genetic Variants in Folate and Cobalamin Metabolism-Related Genes in Pregnant Women of a Homogeneous Spanish Population: The Need for Revisiting the Current Vitamin Supplementation Strategies. Nutrients 2022; 14:nu14132702. [PMID: 35807880 PMCID: PMC9268853 DOI: 10.3390/nu14132702] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 06/23/2022] [Accepted: 06/27/2022] [Indexed: 02/05/2023] Open
Abstract
Polymorphisms of genes involved in the metabolism and transport of folate and cobalamin could play relevant roles in pregnancy outcomes. This study assessed the prevalence of genetic polymorphisms of folate and cobalamin metabolism-related genes such as MTHFR, MTR, CUBN, and SLC19A1 in pregnant women of a homogeneous Spanish population according to conception, pregnancy, delivery, and newborns complications. This study was conducted on 149 nulliparous women with singleton pregnancies. Sociodemographic and obstetrics variables were recorded, and all patients were genotyped in the MTHFR, MTR, CUBN, and SLC10A1 polymorphisms. The distribution of genotypes detected in this cohort was similar to the population distribution reported in Europe, highlighting that more than 50% of women were carriers of risk alleles of the studied genes. In women with the MTHFR risk allele, there was a statistically significant higher frequency of assisted fertilisation and a higher frequency of preeclampsia and preterm birth. Moreover, CUBN (rs1801222) polymorphism carriers showed a statistically significantly lower frequency of complications during delivery. In conclusion, the prevalence of genetic variants related to folic acid and vitamin B12 metabolic genes in pregnant women is related to mother and neonatal outcomes. Knowing the prevalence of these polymorphisms may lead to a personalised prescription of vitamin intake.
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14
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Liu L, Cui H, Huang Y, Zhou Y, Hu J, Wan Y. Enzyme-Mediated Reactions of Phenolic Pollutants and Endogenous Metabolites as an Overlooked Metabolic Disruption Pathway. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2022; 56:3634-3644. [PMID: 35238542 DOI: 10.1021/acs.est.1c08141] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
It is generally recognized that phenol-containing molecules mainly undergo phase II metabolic reactions, whereas glucuronide and sulfate are conjugated to form water-soluble products. Here, we report direct reactions of phenolic pollutants (triclosan, alkylphenol, bisphenol A [BPA], and its analogues) and some endogenous metabolites (vitamin E [VE] and estradiol) to generate new lipophilic ether products (e.g., BPA-O-VEs and alkylphenol-O-estradiol). A nontargeted screening strategy was used to identify the products in human liver microsome incubations, and the most abundant products (BPA-O-VEs) were confirmed via in vivo exposure in mice. BPA-O-VEs were frequently detected in sera from the general population at levels comparable to those of glucuronide/sulfate-conjugated BPA. Recombinant human cytochrome P450s were applied to find that CYP3A4 catalyzed the formation of these newly discovered ether metabolites by linking the VE hydroxyl group to the BPA phenolic ring, leading to the significantly reduced antioxidative activities of BPA-O-VEs compared to VEs. The effects of the reaction on the homeostasis of reacted biomolecules were finally assessed by in vitro assay and in vivo mice exposures. The generation of BPA-O-VEs decreased the VE concentrations and increased the reactive oxygen species generation after exposure to BPA at environmentally relevant concentrations. The identified reactions provided an overlooked metabolic disruption pathway for phenolic pollutants.
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Affiliation(s)
- Liu Liu
- Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China
| | - Hongyang Cui
- Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China
| | - Yixuan Huang
- Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China
| | - Yulan Zhou
- Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China
| | - Jianying Hu
- Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China
| | - Yi Wan
- Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, China
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15
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Zaaboul F, Liu Y. Vitamin E in foodstuff: Nutritional, analytical, and food technology aspects. Compr Rev Food Sci Food Saf 2022; 21:964-998. [PMID: 35181987 DOI: 10.1111/1541-4337.12924] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 11/21/2021] [Accepted: 01/10/2022] [Indexed: 12/16/2022]
Abstract
Vitamin E is a group of isoprenoid chromanols with different biological activities. It comprises eight oil-soluble compounds: four tocopherols, namely, α-, β-, γ-, and δ-tocopherols; and four tocotrienols, namely, α-, β-, γ, and δ-tocotrienols. Vitamin E isomers are well-known for their antioxidant activity, gene-regulation effects, and anti-inflammatory and nephroprotective properties. Considering that vitamin E is exclusively synthesized by photosynthetic organisms, animals can only acquire it through their diet. Plant-based food is the primary source of vitamin E; hence, oils, nuts, fruits, and vegetables with high contents of vitamin E are mostly consumed after processing, including industrial processes and home-cooking, which involve vitamin E profile and content alteration during their preparation. Accordingly, it is essential to identify the vitamin E content and profile in foodstuff to match daily intake requirements. This review summarizes recent advances in vitamin E chemistry, metabolism and metabolites, current knowledge on their contents and profiles in raw and processed plant foods, and finally, their modern developments in analytical methods.
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Affiliation(s)
- Farah Zaaboul
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, People's Republic China
| | - YuanFa Liu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, People's Republic China
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16
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Jiang Q. Metabolism of natural forms of vitamin E and biological actions of vitamin E metabolites. Free Radic Biol Med 2022; 179:375-387. [PMID: 34785321 PMCID: PMC9018116 DOI: 10.1016/j.freeradbiomed.2021.11.012] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 10/29/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022]
Abstract
Natural forms of vitamin E comprise four tocopherols and four tocotrienols. During the last twenty years, there have been breakthroughs in our understanding of vitamin E metabolism and biological activities of vitamin E metabolites. Research has established that tocopherols and tocotrienols are metabolized via ω-hydroxylase (CYP4F2)-initiated side chain oxidation to form 13'-hydroxychromanol and 13'-carobyxychromanol (13'-COOH). 13'-COOHs are further metabolized via β-oxidation and sulfation to intermediate carboxychromanols, terminal metabolite carboxyethyl-hydroxychroman (CEHC), and sulfated analogs. Animal and human studies show that γ-, δ-tocopherol and tocotrienols are more extensively metabolized than α-tocopherol (αT), as indicated by higher formation of CEHCs and 13'-COOHs from non-αT forms than those from αT. 13'-COOHs are shown to be inhibitors of cyclooxygenase-1/-2 and 5-lipoxygenase and much stronger than CEHCs for these activities. 13'-COOHs inhibit cancer cell growth, modulate cellular lipids and activate peroxisome proliferator-activated receptor-γ and pregnane X receptor. Consistent with mechanistic findings, αT-13'-COOH or δTE-13'-COOH, respective metabolites of αT or δ-tocotrienol, show anti-inflammatory and cancer-preventive effects, modulates the gut microbiota and prevents β-amyloid formation in mice. Therefore, 13'-COOHs are a new class of bioactive compounds with anti-inflammatory and anti-cancer activities and potentially capable of modulating lipid and drug metabolism. Based on the existing evidence, this author proposes that metabolites may contribute to disease-preventing effects of γ-, δ-tocopherol and tocotrienols. The role of metabolites in αT's actions may be somewhat limited considering controlled metabolism of αT because of its association with tocopherol-transport protein and less catabolism by CYP4F2 than other vitamin E forms.
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Affiliation(s)
- Qing Jiang
- Department of Nutrition Science, Purdue University, IN, 47907, West Lafayette, USA.
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17
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Willems S, Gellrich L, Chaikuad A, Kluge S, Werz O, Heering J, Knapp S, Lorkowski S, Schubert-Zsilavecz M, Merk D. Endogenous vitamin E metabolites mediate allosteric PPARγ activation with unprecedented co-regulatory interactions. Cell Chem Biol 2021; 28:1489-1500.e8. [PMID: 33989565 DOI: 10.1016/j.chembiol.2021.04.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/29/2021] [Accepted: 04/23/2021] [Indexed: 02/07/2023]
Abstract
Vitamin E exhibits pharmacological effects beyond established antioxidant activity suggesting involvement of unidentified mechanisms. Here, we characterize endogenously formed tocopherol carboxylates and the vitamin E mimetic garcinoic acid (GA) as activators of the peroxisome proliferator-activated receptor gamma (PPARγ). Co-stimulation of PPARγ with GA and the orthosteric agonist pioglitazone resulted in additive transcriptional activity. In line with this, the PPARγ-GA complex adopted a fully active conformation and interestingly contained two bound GA molecules with one at an allosteric site. A co-regulator interaction scan demonstrated an unanticipated co-factor recruitment profile for GA-bound PPARγ compared with canonical PPARγ agonists and gene expression analysis revealed different effects of GA and pioglitazone on PPAR signaling in hepatocytes. These observations reveal allosteric mechanisms of PPARγ modulation as an alternative avenue to PPARγ targeting and suggest contributions of PPARγ activation by α-13-tocopherolcarboxylate to the pharmacological effects of vitamin E.
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Affiliation(s)
- Sabine Willems
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany
| | - Leonie Gellrich
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany
| | - Apirat Chaikuad
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany; Structural Genomics Consortium, BMLS, Goethe University Frankfurt, Frankfurt 60438, Germany
| | - Stefan Kluge
- Chair of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena 07743, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, University of Jena, Jena 07743, Germany
| | - Oliver Werz
- Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Jena 07743, Germany
| | - Jan Heering
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt 60596, Germany
| | - Stefan Knapp
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany; Structural Genomics Consortium, BMLS, Goethe University Frankfurt, Frankfurt 60438, Germany
| | - Stefan Lorkowski
- Chair of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich-Schiller-University Jena, Jena 07743, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, University of Jena, Jena 07743, Germany
| | | | - Daniel Merk
- Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany.
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Favro G, Habib H, Gennity I, Puschner B, Hales EN, Finno CJ, Moeller BC. Determination of vitamin E and its metabolites in equine urine using liquid chromatography-mass spectrometry. Drug Test Anal 2021; 13:1158-1168. [PMID: 33527764 DOI: 10.1002/dta.3006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 01/22/2021] [Accepted: 01/27/2021] [Indexed: 12/20/2022]
Abstract
Equine neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM) is a hereditary, deteriorating central nervous disease in horses. Currently, the only way to confirm eNAD/EDM is through a postmortem histological evaluation of the central nervous system. Vitamin E, specifically the isoform alpha-tocopherol (α-TP), is known to protect eNAD/EDM susceptible horses from developing the clinical phenotype. While vitamin E is an essential nutrient in the diet of horses, there are no diagnostic tests able to quantitate vitamin E and its metabolites in urine. An ultra-performance liquid chromatography-atmospheric-pressure chemical ionization mass spectrometry (UPLC-APCI-MS/MS) method was developed and validated following acidic hydrolysis and solid phase extraction to quantitate vitamin E and its metabolites in equine urine. A blank control horse urine matrix was used and spiked with different concentrations of analytes to form a standard curve using either alpha-tocopherol-d6 or chlorpropamide as the internal standard. Inter-day and intra-day statistics were performed to evaluate the method for accuracy (90% to 116%) and precision (0.75% to 14%). Matrix effects, percent recovery, and stability were also assessed. The method successfully analyzed alpha-carboxyethyl hydroxychroman (α-CEHC), alpha-carboxymethylbutyl hydroxychromans (α-CMBHC), gamma-carboxyethyl hydroxychroman γ-CEHC, and α-TP concentrations in urine to determine a baseline levels of analytes in healthy horses, and can be used to determine concentrations of vitamin E metabolites in equine urine allowing for its evaluation as a diagnostic approach in the treatment of eNAD/EDM.
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Affiliation(s)
- Gianna Favro
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA
| | - Hadi Habib
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA
| | - Ingrid Gennity
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA
| | - Birgit Puschner
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA
| | - Erin N Hales
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA
| | - Carrie J Finno
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA
| | - Benjamin C Moeller
- K. L. Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA
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19
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de Oliveira VA, Pereira IC, Nogueira TR, Martins JA, Péres-Rodrigues G, de Jesus e Silva de Almendra B, Silva VC, Júnior DD, Leal FL, de Castro e Sousa JM, da Silva FC, de Carvalho Melo Cavalcanti AA, de Azevedo Paiva A. The Role of Vitamin E in Breast Cancer Treatment and Prevention: Current Perspectives. CURRENT NUTRITION & FOOD SCIENCE 2021. [DOI: 10.2174/1573401316999200614164711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Regarding the multifactorial etiology of breast cancer, food choices, as well
as dietary intake, are the main modified factors in cancer prevention. In this sense, understanding
molecular pathways involved in breast cancer proliferation can help determine the mechanisms of
action of organic compounds such as antioxidant vitamins that are known to protect against cancer.
Objective:
Assess the mechanism of action of vitamin E in breast cancer modulation, with emphasis
on important markers of tumor development.
Methods:
It is a systematic review carried out in PubMed and Web of Science databases, from the
last 5 years, in Portuguese, English and Spanish. The following terms were selected according to The
Medical Subject Headings (MeSH): “breast cancer” OR “breast neoplasms”, “tocopherol” OR
“tocotrienols” OR “vitamin E”, as equated terms.
Results:
A total of 595 articles were found and 25 were selected according to inclusion criteria.
Vitamin E has been related to suppression/overexpression of important tumorigenic pathways,
mainly associated with proliferation, energy metabolism, chemosensitivity and invasion/metastasis.
Clinical studies of vitamin E supplementation are needed to assess the dose/response effect on breast
cancer patients.
Conclusion:
The safety of vitamin E supplementation is still controversial due to current studies design
available. However, when vitamin E is supplemented, the dose and therapeutic regimen must be
carefully decided, including the route of administration and breast cancer subtypes to enhance
desired effects and minimize unwanted side effects.
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Affiliation(s)
- Victor A. de Oliveira
- Department of Nutrition, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | - Irislene C. Pereira
- Postgraduate Program in Food and Nutrition, Department of Nutrition, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | - Thaís R. Nogueira
- Postgraduate Program in Food and Nutrition, Department of Nutrition, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | - Jorddam A. Martins
- Postgraduate Program in Food and Nutrition, Department of Nutrition, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | | | | | - Vladimir C. Silva
- Department of Biochemistry and Pharmacology, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | - Dalton D. Júnior
- Department of Biochemistry and Pharmacology, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | - Francisco L.T. Leal
- Department of Biophysics and Physiology, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | - Joáo M. de Castro e Sousa
- Department of Biochemistry and Pharmacology, Federal University of Piaui, UFPI, Piaui State, Teresina, Brazil
| | - Felipe C.C. da Silva
- Department of Biology, Federal University of Piaui, UFPI, Piaui State, Picos, Brazil
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20
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Niforou A, Konstantinidou V, Naska A. Genetic Variants Shaping Inter-individual Differences in Response to Dietary Intakes-A Narrative Review of the Case of Vitamins. Front Nutr 2020; 7:558598. [PMID: 33335908 PMCID: PMC7736113 DOI: 10.3389/fnut.2020.558598] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Accepted: 11/03/2020] [Indexed: 12/17/2022] Open
Abstract
Recent advances in the field of nutrigenetics have provided evidence on how genetic variations can impact the individuals' response to dietary intakes. An objective and reliable assessment of dietary exposures should rely on combinations of methodologies including frequency questionnaires, short-term recalls or records, together with biological samples to evaluate markers of intake or status and to identify genetic susceptibilities. In an attempt to present current knowledge on how genetic fingerprints contribute to an individual's nutritional status, we present a review of current literature describing associations between genetic variants and levels of well-established biomarkers of vitamin status in free-living and generally healthy individuals. Based on the outcomes of candidate gene, genome-wide-association studies and meta-analyses thereof, we have identified several single nucleotide polymorphisms (SNPs) involved in the vitamins' metabolic pathways. Polymorphisms in genes encoding proteins involved in vitamin metabolism and transport are reported to have an impact on vitamin D status; while genetic variants of vitamin D receptor were most frequently associated with health outcomes. Genetic variations that can influence vitamin E status include SNPs involved in its uptake and transport, such as in SCAR-B1 gene, and in lipoprotein metabolism. Variants of the genes encoding the sodium-dependent vitamin C transport proteins are greatly associated with the body's status on vitamin C. Regarding the vitamins of the B-complex, special reference is made to the widely studied variant in the MTHFR gene. Methodological attributes of genetic studies that may limit the comparability and interpretability of the findings are also discussed. Our understanding of how genes affect our responses to nutritional triggers will enhance our capacity to evaluate dietary exposure and design personalized nutrition programs to sustain health and prevent disease.
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Affiliation(s)
- Aikaterini Niforou
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Androniki Naska
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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21
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Gujarathi S, Zafar MK, Liu X, Eoff RL, Zheng G. A Facile Semisynthesis and Evaluation of Garcinoic Acid and Its Analogs for the Inhibition of Human DNA Polymerase β. Molecules 2020; 25:E5847. [PMID: 33322249 PMCID: PMC7763917 DOI: 10.3390/molecules25245847] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 12/09/2020] [Indexed: 11/17/2022] Open
Abstract
Garcinoic acid has been identified as an inhibitor of DNA polymerase β (pol β). However, no structure-activity relationship (SAR) studies of garcinoic acid as a pol β inhibitor have been conducted, in part due to the lack of an efficient synthetic method for this natural product and its analogs. We developed an efficient semi-synthetic method for garcinoic acid and its analogs by starting from natural product δ-tocotrienol. Our preliminary SAR studies provided a valuable insight into future discovery of garcinoic acid-based pol β inhibitors.
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Affiliation(s)
- Satheesh Gujarathi
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (S.G.); (X.L.)
| | - Maroof Khan Zafar
- Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (M.K.Z.); (R.L.E.)
| | - Xingui Liu
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (S.G.); (X.L.)
| | - Robert L. Eoff
- Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (M.K.Z.); (R.L.E.)
| | - Guangrong Zheng
- Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; (S.G.); (X.L.)
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
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22
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Synthesis of [ 18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics. Molecules 2020; 25:molecules25235700. [PMID: 33287202 PMCID: PMC7730577 DOI: 10.3390/molecules25235700] [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] [Received: 10/30/2020] [Revised: 11/20/2020] [Accepted: 11/30/2020] [Indexed: 12/04/2022] Open
Abstract
Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E’s biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[18F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([18F]F-γ-T-3) was prepared for this purpose. [18F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [18F]fluoride in DMF/K222. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [18F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [18F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [18F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.
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23
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Martini S, Tagliazucchi D, Minelli G, Lo Fiego DP. Influence of linseed and antioxidant-rich diets in pig nutrition on lipid oxidation during cooking and in vitro digestion of pork. Food Res Int 2020; 137:109528. [PMID: 33233160 DOI: 10.1016/j.foodres.2020.109528] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 06/25/2020] [Accepted: 07/08/2020] [Indexed: 11/18/2022]
Abstract
Enrichment of pig diets with polyunsaturated fatty acids (PUFA) is considered an emerging strategy to increase their intake in the human diet. However, PUFA are particularly vulnerable to oxidative reactions leading to the generation of toxic compounds. The aim of this study was to evaluate the effect of supplementation of pig diets with extruded linseed (L), either or not in combination with synthetic antioxidants (E, tocopheryl-acetate and selenium) or natural extracts (P, grape-skin and oregano), and basal diet (C, without linseed) on the oxidative stability in raw, grilled and in vitro digested pork. The diet supplementation with antioxidant-rich ingredients resulted in the accumulation of specific metabolites in meat. Actually, 11 different phenolic- and 6 tocopherol-derived metabolites were identified by UHPLC/HR-MS. These metabolites were potentially correlated with the reduction in the oxidative phenomena occurring during meat cooking and digestion. Specifically, 16% and 35% reduction in the amounts of lipid hydroperoxides and TBA-RS were assessed after cooking of meat from P diet, respect to the L diet. Diet supplementations with α-tocopheryl acetate and selenium reduced the oxidative reactions only during meat cooking. A significant reduction was attended at the end of in vitro digestion, showing about 24% and 34% hydroperoxides and TBA-RS concentration reductions, respectively, in P diet samples respect to the L ones. Thus, our study suggests that the appearance of phenolic metabolites in meat could be associated to a reduction in the oxidative phenomena during meat cooking and digestion.
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Affiliation(s)
- Serena Martini
- Department of Life Sciences, University of Modena and Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy.
| | - Davide Tagliazucchi
- Department of Life Sciences, University of Modena and Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy; Interdepartmental Research Centre for Agri-Food Biological Resources Improvement and Valorisation (BIOGEST-SITEIA), University of Modena and Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy
| | - Giovanna Minelli
- Department of Life Sciences, University of Modena and Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy; Interdepartmental Research Centre for Agri-Food Biological Resources Improvement and Valorisation (BIOGEST-SITEIA), University of Modena and Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy
| | - Domenico Pietro Lo Fiego
- Department of Life Sciences, University of Modena and Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy; Interdepartmental Research Centre for Agri-Food Biological Resources Improvement and Valorisation (BIOGEST-SITEIA), University of Modena and Reggio Emilia, Via Amendola 2, 42122 Reggio Emilia, Italy
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Amer S, Zarad W, El-Gendy H, Abdel-Salam R, Hadad G, Emara S, Masujima T. Dilute-and-shoot-based direct nano-electrospray ionization tandem mass spectrometry as screening methodology for multivitamins in dietary supplement and human urine. J Adv Res 2020; 26:1-13. [PMID: 33133679 PMCID: PMC7584677 DOI: 10.1016/j.jare.2020.06.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 05/25/2020] [Accepted: 06/09/2020] [Indexed: 11/26/2022] Open
Abstract
INTRODUCTION In recent years, analytical screening methods for simultaneous detection of multivitamins have gained substantial attention to ensure quality and public confidence in dietary supplements. Even so, few analytical methods have been proposed for simultaneous analysis of multivitamin constituents due to the large divergence in chemical characteristics. OBJECTIVES In the present study, the objective was to develop a simple and rapid direct nano-electrospray ionization-tandem mass spectrometry (DI-nano-ESI-MS/MS) method for targeted detection of water soluble vitamins, fat soluble vitamins, amino acids, royal jelly, ginkgo biloba, and ginseng in a dietary supplement. The applicability of dilute-and-shoot-based DI-nano-ESI-MS/MS to analyze the same tested compounds and their related metabolites in clinical samples was also examined. METHODS Intact urine mixed with the ionization solvent was loaded (4-μL aliquot) into a nanospray (NS) capillary of 1-μm tip diameter. The NS capillary was then fitted into an off-line ion source at a distance of 5 mm from MS aperture. The sample was directly injected by applying a voltage of 1.1 kV, producing a numerous of m/z peaks for analysis in mere minutes. RESULTS The DI-nano-ESI-MS/MS method successfully identified almost all dietary supplement components, as well as a plethora of component-related metabolites in clinical samples. In addition, a new merit of the proposed method for the detection of index marker and chemical contaminants as well as subspecies identification was investigated for further quality evaluation of the dietary supplement. CONCLUSIONS The previous findings illustrated that DI-nano-ESI-MS/MS approach can emerge as a powerful, high throughput, and promising analytical tool for screening and accurate detection of various pharmaceuticals and ingredient in dietary supplements as well as biological fluids.
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Affiliation(s)
- Sara Amer
- Faculty of Pharmacy, Misr International University, Km 28 Ismailia Road, Cairo, Egypt
- Quantitative Biology Center (QBiC), RIKEN, 6-2-3 Furuedai, Suita, Osaka 565–0874, Japan
| | - Walaa Zarad
- Faculty of Pharmacy, Misr International University, Km 28 Ismailia Road, Cairo, Egypt
| | - Heba El-Gendy
- Faculty of Pharmacy, Misr International University, Km 28 Ismailia Road, Cairo, Egypt
| | - Randa Abdel-Salam
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Canal Suez University, Ismailia, Egypt
| | - Ghada Hadad
- Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Canal Suez University, Ismailia, Egypt
| | - Samy Emara
- Faculty of Pharmacy, Misr International University, Km 28 Ismailia Road, Cairo, Egypt
| | - Tsutomu Masujima
- Quantitative Biology Center (QBiC), RIKEN, 6-2-3 Furuedai, Suita, Osaka 565–0874, Japan
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Irías-Mata A, Sus N, Hug ML, Müller M, Vetter W, Frank J. α-Tocomonoenol Is Bioavailable in Mice and May Partly Be Regulated by the Function of the Hepatic α‑Tocopherol Transfer Protein. Molecules 2020; 25:molecules25204803. [PMID: 33086686 PMCID: PMC7588010 DOI: 10.3390/molecules25204803] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 09/30/2020] [Accepted: 10/15/2020] [Indexed: 11/16/2022] Open
Abstract
Tocomonoenols are vitamin E derivatives present in foods with a single double bond at carbon 11' in the sidechain. The α-tocopherol transfer protein (TTP) is required for the maintenance of normal α-tocopherol (αT) concentrations. Its role in the tissue distribution of α-11'-tocomonoenol (αT1) is unknown. We investigated the tissue distribution of αT1 and αT in wild-type (TTP+/+) and TTP knockout (TTP-/-) mice fed diets with either αT or αT1 for two weeks. αT1 was only found in blood, not tissues. αT concentrations in TTP+/+ mice were in the order of adipose tissue > brain > heart > spleen > lungs > kidneys > small intestine > liver. Loss of TTP function depleted αT in all tissues. αT1, contrary to αT, was still present in the blood of TTP-/- mice (16% of αT1 in TTP+/+). Autoclaving and storage at room temperature reduced αT and αT1 in experimental diets. In conclusion, αT1 is bioavailable, reaches the blood in mice, and may not entirely depend on TTP function for secretion into the systemic circulation. However, due to instability of the test compounds in the experimental diets, further in vivo experiments are required to clarify the role of TTP in αT1 secretion. Future research should consider compound stability during autoclaving of rodent feed.
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Affiliation(s)
- Andrea Irías-Mata
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, Garbenstr. 28, D-70599 Stuttgart, Germany; (A.I.-M.); (N.S.); (M.-L.H.)
| | - Nadine Sus
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, Garbenstr. 28, D-70599 Stuttgart, Germany; (A.I.-M.); (N.S.); (M.-L.H.)
| | - Maria-Lena Hug
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, Garbenstr. 28, D-70599 Stuttgart, Germany; (A.I.-M.); (N.S.); (M.-L.H.)
| | - Marco Müller
- Institute of Food Chemistry, University of Hohenheim, D-70599 Stuttgart, Germany; (M.M.); (W.V.)
| | - Walter Vetter
- Institute of Food Chemistry, University of Hohenheim, D-70599 Stuttgart, Germany; (M.M.); (W.V.)
| | - Jan Frank
- Department of Food Biofunctionality, Institute of Nutritional Sciences, University of Hohenheim, Garbenstr. 28, D-70599 Stuttgart, Germany; (A.I.-M.); (N.S.); (M.-L.H.)
- Correspondence: ; Tel.: +49-711-459-24459; Fax: +49-711-459-23386
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LC-MS/MS quantification of fat soluble vitamers - A systematic review. Anal Biochem 2020; 613:113980. [PMID: 33065116 DOI: 10.1016/j.ab.2020.113980] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 07/12/2020] [Accepted: 09/28/2020] [Indexed: 11/24/2022]
Abstract
Fat soluble vitamers (FSV) are several biochemically diverse micronutrients essential for healthy development, growth, metabolism, and cell regulation. We cannot synthesize FSV completely or at the required concentrations. Deficiency or excess of FSV can result in many health problems. Plasma is the most accessible sample matrix for the quantification of FSV. However, due to its complexity and other analytical challenges (e.g., FSV sensitivity to light, oxygen, heat, pH, chemical heterogeneity, standard availability), developing a method for the simultaneous quantification of multiple FSV at physiological concentrations has been challenging. In this systematic review, we examine the parameters and criteria used in existing Liquid Chromatography with tandem Mass Spectrometry (LC-MS/MS) methods for FSV quantification to the extraction method, chromatographic resolution, matrix effects, and method validation as critical to a sensitive and robust method. We conclude that the final FSV method sensitivity is predominantly based on aforementioned criteria and future method development using LC-MS/MS will benefit from the application of this systematic review.
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Changes in the Fecal Metabolome Are Associated with Feeding Fiber Not Health Status in Cats with Chronic Kidney Disease. Metabolites 2020; 10:metabo10070281. [PMID: 32660033 PMCID: PMC7407581 DOI: 10.3390/metabo10070281] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 07/03/2020] [Accepted: 07/03/2020] [Indexed: 11/25/2022] Open
Abstract
The objective was to determine the effects of feeding different fiber sources to cats with chronic kidney disease (CKD) compared with healthy cats (both n = 10) on fecal metabolites. A cross-over within split-plot study design was performed using healthy and CKD cats (IRIS stage 1, 2, and 3). After cats were fed a complete and balanced dry food designed to aid in the management of renal disease for 14 days during a pre-trial period, they were randomly assigned to two fiber treatments for 4 weeks each. The treatment foods were formulated similar to pre-trial food and contained 0.500% betaine, 0.586% oat beta glucan, and either 0.407% short chain fructooligosaccharides (scFOS) fiber or 3.44% apple pomace. Both treatment foods had similar crude fiber (2.0 and 2.1% for scFOS and apple pomace, respectively) whereas soluble fiber was 0.8 and 1.6%, respectively. At baseline, CKD had very little impact on the fecal metabolome. After feeding both fiber sources, some fecal metabolite concentrations were significantly different compared with baseline. Many fecal uremic toxins decreased, although in healthy cats some increased; and some more so when feeding apple pomace compared with scFOS, e.g., hippurate, 4-hydroxyhippurate, and 4-methylcatechol sulfate; the latter was also increased in CKD cats. Changes in secondary bile acid concentrations were more numerous in healthy compared with CKD cats, and cats in both groups had greater increases in some secondary bile acids after consuming apple pomace compared with scFOS, e.g., tauroursodeoxycholate and hyocholate. Although changes associated with feeding fiber were more significant than changes associated with disease status, differential modulation of the gut-kidney axis using dietary fiber may benefit cats.
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Ayusman S, Duraivadivel P, Gowtham H, Sharma S, Hariprasad P. Bioactive constituents, vitamin analysis, antioxidant capacity and α-glucosidase inhibition of Canna indica L. rhizome extracts. FOOD BIOSCI 2020. [DOI: 10.1016/j.fbio.2020.100544] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Wallert M, Kluge S, Schubert M, Koeberle A, Werz O, Birringer M, Lorkowski S. Diversity of Chromanol and Chromenol Structures and Functions: An Emerging Class of Anti-Inflammatory and Anti-Carcinogenic Agents. Front Pharmacol 2020; 11:362. [PMID: 32372948 PMCID: PMC7187200 DOI: 10.3389/fphar.2020.00362] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 03/10/2020] [Indexed: 12/31/2022] Open
Abstract
Natural chromanols and chromenols comprise a family of molecules with enormous structural diversity and biological activities of pharmacological interest. A recently published systematic review described more than 230 structures that are derived from a chromanol ortpd chromenol core. For many of these compounds structure-activity relationships have been described with mostly anti-inflammatory as well as anti-carcinogenic activities. To extend the knowledge on the biological activity and the therapeutic potential of these promising class of natural compounds, we here present a report on selected chromanols and chromenols based on the availability of data on signaling pathways involved in inflammation, apoptosis, cell proliferation, and carcinogenesis. The chromanol and chromenol derivatives seem to bind or to interfere with several molecular targets and pathways, including 5-lipoxygenase, nuclear receptors, and the nuclear-factor "kappa-light-chain-enhancer" of activated B-cells (NFκB) pathway. Interestingly, available data suggest that the chromanols and chromenols are promiscuitively acting molecules that inhibit enzyme activities, bind to cellular receptors, and modulate mitochondrial function as well as gene expression. It is also noteworthy that the molecular modes of actions by which the chromanols and chromenols exert their effects strongly depend on the concentrations of the compounds. Thereby, low- and high-affinity molecular targets can be classified. This review summarizes the available knowledge on the biological activity of selected chromanols and chromenols which may represent interesting lead structures for the development of therapeutic anti-inflammatory and chemopreventive approaches.
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Affiliation(s)
- Maria Wallert
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
| | - Stefan Kluge
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
| | - Martin Schubert
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
| | - Andreas Koeberle
- Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany
- Michael Popp Research Institute, University of Innsbruck, Innsbruck, Austria
| | - Oliver Werz
- Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany
| | - Marc Birringer
- Department of Nutrition, Food and Consumer Sciences, University of Applied Sciences Fulda, Fulda, Germany
- Regionales Innovationszentrum Gesundheit und Lebensqualität (RIGL), Fulda, Germany
| | - Stefan Lorkowski
- Department of Biochemistry and Physiology of Nutrition, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Jena, Germany
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Ran L, Liu AB, Lee MJ, Xie P, Lin Y, Yang CS. Effects of antibiotics on degradation and bioavailability of different vitamin E forms in mice. Biofactors 2019; 45:450-462. [PMID: 30694588 DOI: 10.1002/biof.1492] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 12/10/2018] [Accepted: 12/29/2018] [Indexed: 12/18/2022]
Abstract
Tocopherols (T) and tocotrienols (T3), all existing in α, β, γ, and δ-forms, are the eight forms of vitamin E (VE). In this study, we investigated the effects of gut microbiota on the degradation and tissue levels of different VE forms by treating mice with antibiotics in drinking water for 12 days. The mice also received an intragastric (i.g.) dose of VE mixture (mVE; α-T, γ-T, δ-T, γ-T3, and δ-T3, each at a dose of 75 mg/kg) every morning. Antibiotic treatment significantly increased the blood levels of all VE forms in mice that received an i.g. dose of mVE in the morning, 3 h before sacrifice. Without this morning dose, the blood levels of α-T were at the normal physiological levels, but those of the other VE forms were much lower; and the levels of all VE forms were not significantly affected by antibiotics. The liver levels of these VE forms were generally higher and followed the same pattern as the serum. On the contrary, the levels of most side-chain degradation metabolites of VE forms in the serum, liver, kidney, urine, and fecal samples were significantly decreased by antibiotics. The increased bioavailability of VE by antibiotics is probably due to increased absorption of VE or its decreased degradation by gut microbes. The results demonstrate the important roles of gut microbiota in the degradation of VE and in decreasing the bioavailabilities of VE forms. © 2019 BioFactors, 45(3):450-462, 2019.
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Affiliation(s)
- Linwu Ran
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
- Ningxia Medical University, Yinchuan, Ningxia, China
| | - Anna B Liu
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
| | - Mao-Jung Lee
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
| | - Ping Xie
- Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - Yong Lin
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
- Department of Biostatistics, School of Public Health, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
| | - Chung S Yang
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
- Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
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31
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Comparison of the microbiome, metabolome, and lipidome of obese and non-obese horses. PLoS One 2019; 14:e0215918. [PMID: 31013335 PMCID: PMC6478336 DOI: 10.1371/journal.pone.0215918] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 04/10/2019] [Indexed: 12/12/2022] Open
Abstract
Metabolic diseases such as obesity and type 2 diabetes in humans have been linked to alterations in the gastrointestinal microbiota and metabolome. Knowledge of these associations has improved our understanding of the pathophysiology of these diseases and guided development of diagnostic biomarkers and therapeutic interventions. The cellular and molecular pathophysiology of equine metabolic syndrome (EMS) and obesity in horses, however, remain ill-defined. Thus, the objectives of this study were to characterize the fecal microbiome, fecal metabolome, and circulating lipidome in obese and non-obese horses. The fecal microbiota, fecal metabolome, and serum lipidome were evaluated in obese (case) horses (n = 20) and non-obese (control) horses (n = 20) matched by farm of origin (n = 7). Significant differences in metabolites of the mitochondrial tricarboxylic acid cycle and circulating free fatty acids were identified in the obese horses compared to the non-obese horses. These results indicate that the host and bacterial metabolism should be considered important in obese horses. Further studies to determine whether these associations are causal and the mechanistic basis of the association are warranted because they might reveal diagnostic biomarkers and therapeutic interventions to mitigate obesity, EMS, and sequelae including laminitis.
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32
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Nawrot-Hadzik I, Ślusarczyk S, Granica S, Hadzik J, Matkowski A. Phytochemical Diversity in Rhizomes of Three Reynoutria Species and their Antioxidant Activity Correlations Elucidated by LC-ESI-MS/MS Analysis. Molecules 2019; 24:E1136. [PMID: 30901974 PMCID: PMC6470775 DOI: 10.3390/molecules24061136] [Citation(s) in RCA: 31] [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: 02/25/2019] [Revised: 03/11/2019] [Accepted: 03/14/2019] [Indexed: 11/16/2022] Open
Abstract
The rhizome of Reynoutria japonica is a well-known traditional herb (Hu zhang) used in East Asia to treat various inflammatory diseases, infections, skin diseases, scald, and hyperlipidemia. It is also one of the richest natural sources of resveratrol. Although, it has been recently included in the European Pharmacopoeia, in Europe it is still an untapped resource. Some of the therapeutic effects are likely to be influenced by its antioxidant properties and this in turn is frequently associated with a high stilbene content. However, compounds other than stilbenes may add to the total antioxidant capacity. Hence, the aim of this research was to examine rhizomes of R. japonica and the less studied but morphologically similar species, R. sachalinensis and R. x bohemica for their phytochemical composition and antioxidant activity and to clarify the relationship between the antioxidant activity and the components by statistical methods. HPLC/UV/ESI-MS studies of three Reynoutria species revealed 171 compounds, comprising stilbenes, carbohydrates, procyanidins, flavan-3-ols, anthraquinones, phenylpropanoids, lignin oligomers, hydroxycinnamic acids, naphthalenes and their derivatives. Our studies confirmed the presence of procyanidins with high degree of polymerization, up to decamers, in the rhizomes of R. japonica and provides new data on the presence of these compounds in other Reynoutria species. A procyanidin trimer digallate was described for the first time in, the studied plants. Moreover, we tentatively identified dianthrone glycosides new for these species and previously unrecorded phenylpropanoid disaccharide esters and hydroxycinnamic acid derivatives. Furthermore, compounds tentatively annotated as lignin oligomers were observed for the first time in the studied species. The rhizomes of all Reynoutria species exhibited strong antioxidant activity. Statistical analysis demonstrated that proanthocyanidins should be considered as important contributors to the total antioxidant capacity.
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Affiliation(s)
- Izabela Nawrot-Hadzik
- Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, 50-367 Wrocław, Poland.
| | - Sylwester Ślusarczyk
- Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, 50-367 Wrocław, Poland.
| | - Sebastian Granica
- Department of Pharmacognosy and Molecular Foundations of Phytotherapy, Warsaw Medical University, 02-097 Warszawa, Poland.
| | - Jakub Hadzik
- Department of Dental Surgery, Wroclaw Medical University, 50-425 Wrocław, Poland.
| | - Adam Matkowski
- Department of Pharmaceutical Biology and Botany, Wroclaw Medical University, 50-367 Wrocław, Poland.
- Botanical Garden of Medicinal Plants, Wroclaw Medical University, 50-367 Wrocław, Poland.
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33
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Sozen E, Demirel T, Ozer NK. Vitamin E: Regulatory role in the cardiovascular system. IUBMB Life 2019; 71:507-515. [PMID: 30779288 DOI: 10.1002/iub.2020] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 01/24/2019] [Indexed: 12/22/2022]
Abstract
Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality, all around the world. Vitamin E is an important nutrient influencing key cellular and molecular mechanisms as well as gene expression regulation centrally involved in the prevention of CVD. Cell culture and animal studies have focused on the identification of vitamin E regulated signaling pathways and involvement on inflammation, lipid homeostasis, and atherosclerotic plaque stability. While some of these vitamin E functions were verified in clinical trials, some of the positive effects were not translated into beneficial outcomes in epidemiological studies. In recent years, the physiological metabolites of vitamin E, including the liver derived (long- and short-chain) metabolites and phosphorylated (α-, γ-tocopheryl phosphate) forms, have also provided novel mechanistic insight into CVD regulation that expands beyond the vitamin E precursor. It is certain that this emerging insight into the molecular and cellular action of vitamin E will help to design further studies, either in animal models or clinical trials, on the reduction of risk for CVDs. This review focuses on vitamin E-mediated preventive cardiovascular effects and discusses novel insights into the biology and mechanism of action of vitamin E metabolites in CVD. © 2019 IUBMB Life, 71(4):507-515, 2019.
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Affiliation(s)
- Erdi Sozen
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Istanbul, Turkey
| | - Tugce Demirel
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Istanbul, Turkey
| | - Nesrin Kartal Ozer
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Istanbul, Turkey
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Fiume MM, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC, Marks JG, Shank RC, Slaga TJ, Snyder PW, Andersen FA, Heldreth B. Safety Assessment of Tocopherols and Tocotrienols as Used in Cosmetics. Int J Toxicol 2019; 37:61S-94S. [PMID: 30235959 DOI: 10.1177/1091581818794455] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 14 tocopherols and tocotrienols and concluded these ingredients are safe as used in cosmetics. The tocopherols are reported to function in cosmetics as antioxidants or skin-conditioning agents; in contrast, tocotrienols are not reported to function as an antioxidants in cosmetics but as a light stabilizer, oral care agent, or skin-conditioning agent. The Panel reviewed the new and existing animal and clinical data to determine the safety of these ingredients and found it appropriate to extrapolate the existing information to conclude on the safety of all the tocopherols and tocotrienols.
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Affiliation(s)
- Monice M Fiume
- 1 Cosmetic Ingredient Review Senior Director, Cosmetic Ingredient Review, Washington, DC, USA
| | - Wilma F Bergfeld
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - Donald V Belsito
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - Ronald A Hill
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - Curtis D Klaassen
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - Daniel C Liebler
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - James G Marks
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - Ronald C Shank
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - Thomas J Slaga
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - Paul W Snyder
- 2 Cosmetic Ingredient Review Expert Panel Member, Cosmetic Ingredient Review, Washington, DC, USA
| | - F Alan Andersen
- 3 Cosmetic Ingredient Review Former Director, Cosmetic Ingredient Review, Washington, DC, USA
| | - Bart Heldreth
- 4 Cosmetic Ingredient Review Executive Director, Cosmetic Ingredient Review, Washington, DC, USA
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Birringer M, Lorkowski S. Vitamin E: Regulatory role of metabolites. IUBMB Life 2018; 71:479-486. [PMID: 30578664 DOI: 10.1002/iub.1988] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 11/19/2018] [Accepted: 11/24/2018] [Indexed: 12/19/2022]
Abstract
Vitamin E plays an important role as a lipophilic antioxidant in cellular redox homeostasis. Besides this function, numerous non-antioxidant properties of this vitamin have been discovered in the past. DNA microarray technology revealed a complex regulatory network influenced by the different vitamin E forms (Rimbach et al., Molecules, 15, 1746 (2010); Galli et al., Free Radic. Biol. Med., 102, 16 (2017)); however, little is known about the biological activity of vitamin E metabolites. A new chapter of vitamin E research was been opened when endogenous long-chain tocopherol metabolites were identified and their high biological activity in vitro and in vivo was recognized (Schmölz et al., World J. Biol. Chem., 7, 14 (2016); Torquato et al., J. Pharm. Biomed. Anal., 124, 399 (2016)). Just recently, it was shown that an endogenous metabolite of vitamin E inhibits 5-lipoxygenase at nanomolar concentrations, thereby limiting inflammation (Pein et al., Nat. Commun., 9, 3834 (2018)). Furthermore, long-chain vitamin E metabolites (LCM) exhibit hormone-like activities similar to the lipid soluble vitamins A and D (Galli et al., Free Radic. Biol. Med., 102, 16 (2017); Schubert et al., Antioxidants, 7 (2018)). This review aims at summarizing recent findings on the regulatory activities of vitamin E metabolites, especially of LCMs. © 2018 IUBMB Life, 71(4):479-486, 2019.
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Affiliation(s)
- Marc Birringer
- Department of Nutrition, Food and Consumer Sciences, University of Applied Sciences Fulda, Fulda, Germany
| | - Stefan Lorkowski
- Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Sciences, Friedrich Schiller University Jena, Jena, Germany.,Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany
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Vitamin-supplemented chewing gum can increase salivary and plasma levels of a panel of vitamins in healthy human participants. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.09.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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Bartosińska E, Borsuk-De Moor A, Siluk D, Markuszewski MJ, Wiczling P. Ionization of tocopherols and tocotrienols in atmospheric pressure chemical ionization. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2018; 32:919-927. [PMID: 29578620 DOI: 10.1002/rcm.8124] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 03/15/2018] [Accepted: 03/16/2018] [Indexed: 06/08/2023]
Abstract
RATIONALE Tocopherols and tocotrienols are chemical compounds insusceptible to the ionization process under atmospheric pressure conditions. Therefore, the selection of the optimal ion source settings for their quantification requires special attention. The aim of this study was to analyse the influence of the APCI source parameters on the response of tocochromanols and two related compounds. METHODS Standard solutions of target compounds were injected on the high-performance liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (HPLC/APCI-MS/MS) system separately and analysed with 30 randomly selected ion source settings. The obtained responses were modelled by multivariate linear regression with least absolute shrinkage and selection operator. The developed models were used to choose the best APCI conditions. RESULTS Multivariate linear models were built for eight tocochromanols, trolox and BHT. The APCI settings derived from the models did not increase the peak areas obtained for T and T3 during the ionization process. Ionization conditions based on models for trolox and BHT improved analytical responses by 12-36% and 4-32%, respectively. The application of the ion source settings optimal for trolox and BHT to tocochromanols did not result in better analytical responses. CONCLUSIONS The ionization pattern of tocochromanols in the APCI source is problematic and should be further investigated. Modelling methodology for response improvement presented in this study can be applied in similar studies.
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Affiliation(s)
- Ewa Bartosińska
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland
| | - Agnieszka Borsuk-De Moor
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland
| | - Danuta Siluk
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland
| | - Michał J Markuszewski
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland
| | - Paweł Wiczling
- Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Hallera 107, 80-416, Gdańsk, Poland
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Abstract
The hydrophobicity of vitamin E poses transport and metabolic challenges to regulate its bioavailability and to prevent its accumulation in lipid-rich tissues such as adipose tissue, brain, and liver. Water-soluble precursors of vitamin E (α-tocopherol, αT), such as its esters with acetate (αTA), succinate (αTS), or phosphate (αTP), have increased solubility in water and stability against reaction with free radicals, but they are rapidly converted during their uptake into the lipid-soluble vitamin E. Therefore, the bioavailability of these precursors as intact molecules is low; nevertheless, at least for αTS and αTP, the recent research has revealed unique regulatory effects on signal transduction and gene expression and the modulation of cellular events ranging from proliferation, survival/apoptosis, lipid uptake and metabolism, phagocytosis, long term potentiation, cell migration, telomere maintenance, and angiogenesis. Moreover, water-soluble derivatives of vitamin E including some based on αTP are increasingly used as components of nanocarriers for enhanced and targeted delivery of drugs and other molecules (vitamins, including αT and αTP itself, vitamin D3, carnosine, caffeine, docosahexaenoic acid (DHA), insulin) and cofactors such as coenzyme Q10. In this review, the chemical characteristics, transport, metabolic pathways, and molecular mechanisms of action of αTP in cells and tissues are summarized and put into perspective with its possible role in the prevention of a number of diseases.
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Affiliation(s)
- Jean-Marc Zingg
- Miller School of Medicine, University of Miami, Miami, FL, United States.
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Ultrafast determination of vitamin E using LC–ESI–MS/MS for preclinical development of new nutraceutical formulations. Bioanalysis 2018; 10:215-227. [DOI: 10.4155/bio-2017-0095] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Aim: We proposed a rapid and high quality method to determine α-tocopherol (α-T) in different biopharmaceutical samples using liquid chromatography-diode array detector on-line ESI–MS/MS. Materials & methods: A working standard solution of α-T and internal standard, phenyl-5,7-dimethyl-d6-α-tocopherol, were used for optimization and validation of the method. Levels of α-T in nanoemulsions, serum and plasma samples were evaluated. Results & conclusion: Precision (1% for retention time, 5% for peak area and 3% for relative peak area), linearity range (among 0.625–20.0 μg ml-1), LOD and LOQ, accuracy and matrix effect were studied. The validated chromatographic method is presented as valuable analytical tool for the determination of α-tocopherol in loaded drug delivery systems and in biodistribution levels in blood samples.
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Birringer M, Siems K, Maxones A, Frank J, Lorkowski S. Natural 6-hydroxy-chromanols and -chromenols: structural diversity, biosynthetic pathways and health implications. RSC Adv 2018; 8:4803-4841. [PMID: 35539527 PMCID: PMC9078042 DOI: 10.1039/c7ra11819h] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 01/18/2018] [Indexed: 01/26/2023] Open
Abstract
We present the first comprehensive and systematic review on the structurally diverse toco-chromanols and -chromenols found in photosynthetic organisms, including marine organisms, and as metabolic intermediates in animals. The focus of this work is on the structural diversity of chromanols and chromenols that result from various side chain modifications. We describe more than 230 structures that derive from a 6-hydroxy-chromanol- and 6-hydroxy-chromenol core, respectively, and comprise di-, sesqui-, mono- and hemiterpenes. We assort the compounds into a structure-activity relationship with special emphasis on anti-inflammatory and anti-carcinogenic activities of the congeners. This review covers the literature published from 1970 to 2017.
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Affiliation(s)
- Marc Birringer
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences Leipziger Straße 123 36037 Fulda Germany
| | - Karsten Siems
- AnalytiCon Discovery GmbH Hermannswerder Haus 17 14473 Potsdam Germany
| | - Alexander Maxones
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences Leipziger Straße 123 36037 Fulda Germany
| | - Jan Frank
- Institute of Biological Chemistry and Nutrition, University of Hohenheim Garbenstr. 28 70599 Stuttgart Germany
| | - Stefan Lorkowski
- Institute of Nutrition, Friedrich Schiller University Jena Dornburger Str. 25 07743 Jena Germany
- Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig Germany
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Schubert M, Kluge S, Schmölz L, Wallert M, Galli F, Birringer M, Lorkowski S. Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept for Lipid-Soluble Vitamins? Antioxidants (Basel) 2018; 7:antiox7010010. [PMID: 29329238 PMCID: PMC5789320 DOI: 10.3390/antiox7010010] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 01/05/2018] [Accepted: 01/11/2018] [Indexed: 02/06/2023] Open
Abstract
Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins A and D, a metabolic conversion of precursors to active metabolites has already been described. During the metabolism of vitamin E, the long-chain metabolites (LCMs) 13'-hydroxychromanol (13'-OH) and 13'-carboxychromanol (13'-COOH) are formed by oxidative modification of the side-chain. The occurrence of these metabolites in human serum indicates a physiological relevance. Indeed, effects of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory actions as well as tocopherol and xenobiotic metabolism have been shown. Interestingly, there are several parallels between the actions of the LCMs of vitamin E and the active metabolites of vitamin A and D. The recent findings that the LCMs exert effects different from that of their precursors support their putative role as regulatory metabolites. Hence, it could be proposed that the mode of action of the LCMs might be mediated by a mechanism similar to vitamin A and D metabolites. If the physiological relevance and this concept of action of the LCMs can be confirmed, a general concept of activation of lipid-soluble vitamins via their metabolites might be deduced.
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Affiliation(s)
- Martin Schubert
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
| | - Stefan Kluge
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
| | - Lisa Schmölz
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
| | - Maria Wallert
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Baker IDI Heart and Diabetes Institute, Melbourne VIC 3004, Australia.
| | - Francesco Galli
- Department of Pharmaceutical Sciences, Laboratory of Nutrition and Clinical Biochemistry, University of Perugia, 06123 Perugia, Italy.
| | - Marc Birringer
- Department of Nutrition, Food and Consumer Sciences, University of Applied Sciences Fulda, 36037 Fulda, Germany.
| | - Stefan Lorkowski
- Department of Biochemistry and Physiology of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
- Competence Center for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, 07743 Jena, Germany.
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Lee MJ, Feng W, Yang L, Chen YK, Chi E, Liu A, Yang CS. Methods for efficient analysis of tocopherols, tocotrienols and their metabolites in animal samples with HPLC-EC. J Food Drug Anal 2018; 26:318-329. [PMID: 29389570 PMCID: PMC9332665 DOI: 10.1016/j.jfda.2017.07.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 07/19/2017] [Accepted: 07/21/2017] [Indexed: 12/14/2022] Open
Abstract
Tocopherols and tocotrienols, collectively known as vitamin E, have received a great deal of attention because of their interesting biological activities. In the present study, we reexamined and improved previous methods of sample preparation and the conditions of high-performance liquid chromatography for more accurate quantification of tocopherols, tocotrienols and their major chain-degradation metabolites. For the analysis of serum tocopherols/tocotrienols, we reconfirmed our method of mixing serum with ethanol followed by hexane extraction. For the analysis of tissue samples, we improved our methods by extracting tocopherols/tocotrienols directly from tissue homogenate with hexane. For the analysis of total amounts (conjugated and unconjugated forms) of side-chain degradation metabolites, the samples need to be deconjugated by incubating with β-glucuronidase and sulfatase; serum samples can be directly used for the incubation, whereas for tissue homogenates a pre-deproteination step is needed. The present methods are sensitive, convenient and are suitable for the determination of different forms of vitamin E and their metabolites in animal and human studies. Results from the analysis of serum, liver, kidney, lung and urine samples from mice that had been treated with mixtures of tocotrienols and tocopherols are presented as examples.
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Allen L, Ramalingam L, Menikdiwela K, Scoggin S, Shen CL, Tomison MD, Kaur G, Dufour JM, Chung E, Kalupahana NS, Moustaid-Moussa N. Effects of delta-tocotrienol on obesity-related adipocyte hypertrophy, inflammation and hepatic steatosis in high-fat-fed mice. J Nutr Biochem 2017; 48:128-137. [DOI: 10.1016/j.jnutbio.2017.07.003] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2017] [Revised: 05/30/2017] [Accepted: 07/07/2017] [Indexed: 12/23/2022]
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Giusepponi D, Torquato P, Bartolini D, Piroddi M, Birringer M, Lorkowski S, Libetta C, Cruciani G, Moretti S, Saluti G, Galli F, Galarini R. Determination of tocopherols and their metabolites by liquid-chromatography coupled with tandem mass spectrometry in human plasma and serum. Talanta 2017; 170:552-561. [PMID: 28501210 DOI: 10.1016/j.talanta.2017.04.030] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 04/06/2017] [Accepted: 04/11/2017] [Indexed: 12/25/2022]
Abstract
Several studies are increasingly underlying the biological role of vitamin E metabolites as bioactive compounds with anti-inflammatory, anti-proliferative and anti-atherogenic activity. A quantitative method for the simultaneous determination in human plasma and serum of vitamin E (α-tocopherol, α-T and γ-tocopherol, γ-T) and its cytochrome P-450 metabolites: 13'-hydroxychromanol (α-13'-OH), 13'-carboxychromanol (α-13'-COOH) and carboxyethyl hydroxychromanols (α-CEHC and γ-CEHC), was developed and validated. After enzymatic hydrolysis and deproteinization, the metabolites were extracted with a mixture of hexane/ methyl tertiary butyl ether (2/1, v/v). The separation was achieved by reversed phase chromatography and the analytes detected by a triple quadrupole mass analyser using electrospray ionization in positive mode (LC-MS/MS). α-T and γ-T were extracted separately without enzymatic hydrolysis. The analytes were quantified with the isotopic dilution method. After an extensive validation study (three levels in three different occasions for a total of 54 experiments), the procedure was successfully applied to the analysis of sera of healthy volunteers (before and after supplementation with α-T) and plasma of patients affected by chronic kidney disease. Finally, the structures of three unknown compounds found in blood and related to the long chain metabolites (α-13'-OH and α-13'-COOH) were further investigated using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS).
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Affiliation(s)
- Danilo Giusepponi
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, 06126 Perugia, Italy
| | - Pierangelo Torquato
- Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
| | - Desirée Bartolini
- Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
| | - Marta Piroddi
- Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
| | - Marc Birringer
- Department of Nutritional, Food and Consumer Studies, University of Applied Sciences Fulda, 36037 Fulda, Germany
| | - Stefen Lorkowski
- Department of Nutritional Biochemistry, Institute of Nutrition, Friedrich Schiller University Jena, 07743 Jena, Germany
| | - Carmelo Libetta
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy
| | - Gabriele Cruciani
- Department of Chemistry, Biology and Biotechnology, University of Perugia, 06126 Perugia, Italy
| | - Simone Moretti
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, 06126 Perugia, Italy
| | - Giorgio Saluti
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, 06126 Perugia, Italy
| | - Francesco Galli
- Department of Pharmaceutical Sciences, University of Perugia, 06126 Perugia, Italy
| | - Roberta Galarini
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche, 06126 Perugia, Italy.
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Bak MJ, Das Gupta S, Wahler J, Lee HJ, Li X, Lee MJ, Yang CS, Suh N. Inhibitory Effects of γ- and δ-Tocopherols on Estrogen-Stimulated Breast Cancer In Vitro and In Vivo. Cancer Prev Res (Phila) 2017; 10:188-197. [PMID: 28096236 DOI: 10.1158/1940-6207.capr-16-0223] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 12/24/2016] [Accepted: 01/03/2017] [Indexed: 12/21/2022]
Abstract
Estrogens have been implicated as complete carcinogens for breast and other tissues through mechanisms involving increased cell proliferation, oxidative stress, and DNA damage. Because of their potent antioxidant activity and other effects, tocopherols have been shown to exert antitumor activities in various cancers. However, limited information is available on the effect of different forms of tocopherols in estrogen-mediated breast cancer. To address this, we examined the effects of α-, γ-, and δ-tocopherols as well as a natural γ-tocopherol-rich mixture of tocopherols, γ-TmT, on estrogen-stimulated MCF-7 cells in vitro and in vivo For the in vivo studies, MCF-7 cells were injected into the mammary fat pad of immunodeficient mice previously implanted with estrogen pellets. Mice were then administered diets containing 0.2% α-, γ-, δ-tocopherol, or γ-TmT for 5 weeks. Treatment with α-, γ-, δ-tocopherols, and γ-TmT reduced tumor volumes by 29% (P < 0.05), 45% (P < 0.05), 41% (P < 0.05), and 58% (P < 0.01), as well as tumor weights by 20%, 37% (P < 0.05), 39% (P < 0.05), and 52% (P < 0.05), respectively. γ- and δ-tocopherols and γ-TmT inhibited the expression of cell proliferation-related genes such as cyclin D1 and c-Myc, and estrogen-related genes such as TFF/pS2, cathepsin D, and progesterone receptor in estrogen-stimulated MCF-7 cells in vitro Further, γ- and δ-tocopherols decreased the levels of estrogen-induced oxidative stress and nitrosative stress markers, 8-hydroxy-2'-deoxyguanosine and nitrotyrosine, as well as the DNA damage marker, γ-H2AX. Our results suggest that γ- and δ-tocopherols and the γ-tocopherol-rich mixture are effective natural agents for the prevention and treatment of estrogen-mediated breast cancer. Cancer Prev Res; 10(3); 188-97. ©2017 AACR.
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Affiliation(s)
- Min Ji Bak
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
| | - Soumyasri Das Gupta
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
| | - Joseph Wahler
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
| | - Hong Jin Lee
- Department of Food Science and Technology, Chung-Ang University, Anseong, South Korea
| | - Xiaowei Li
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
| | - Mao-Jung Lee
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
| | - Chung S Yang
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Nanjoo Suh
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
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Galli F, Azzi A, Birringer M, Cook-Mills JM, Eggersdorfer M, Frank J, Cruciani G, Lorkowski S, Özer NK. Vitamin E: Emerging aspects and new directions. Free Radic Biol Med 2017; 102:16-36. [PMID: 27816611 DOI: 10.1016/j.freeradbiomed.2016.09.017] [Citation(s) in RCA: 267] [Impact Index Per Article: 33.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 09/11/2016] [Accepted: 09/22/2016] [Indexed: 12/30/2022]
Abstract
The discovery of vitamin E will have its 100th anniversary in 2022, but we still have more questions than answers regarding the biological functions and the essentiality of vitamin E for human health. Discovered as a factor essential for rat fertility and soon after characterized for its properties of fat-soluble antioxidant, vitamin E was identified to have signaling and gene regulation effects in the 1980s. In the same years the cytochrome P-450 dependent metabolism of vitamin E was characterized and a first series of studies on short-chain carboxyethyl metabolites in the 1990s paved the way to the hypothesis of a biological role for this metabolism alternative to vitamin E catabolism. In the last decade other physiological metabolites of vitamin E have been identified, such as α-tocopheryl phosphate and the long-chain metabolites formed by the ω-hydroxylase activity of cytochrome P-450. Recent findings are consistent with gene regulation and homeostatic roles of these metabolites in different experimental models, such as inflammatory, neuronal and hepatic cells, and in vivo in animal models of acute inflammation. Molecular mechanisms underlying these responses are under investigation in several laboratories and side-glances to research on other fat soluble vitamins may help to move faster in this direction. Other emerging aspects presented in this review paper include novel insights on the mechanisms of reduction of the cardiovascular risk, immunomodulation and antiallergic effects, neuroprotection properties in models of glutamate excitotoxicity and spino-cerebellar damage, hepatoprotection and prevention of liver toxicity by different causes and even therapeutic applications in non-alcoholic steatohepatitis. We here discuss these topics with the aim of stimulating the interest of the scientific community and further research activities that may help to celebrate this anniversary of vitamin E with an in-depth knowledge of its action as vitamin.
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Affiliation(s)
- Francesco Galli
- Department of Pharmaceutical Sciences, University of Perugia, Laboratory of Clinical Biochemistry and Nutrition, Via del Giochetto, 06126 Perugia, Italy.
| | - Angelo Azzi
- USDA-HNRCA at Tufts University, 711 Washington St., Boston, MA 02111, United States.
| | - Marc Birringer
- Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, Leipziger Straße 123, 36037 Fulda, Germany.
| | - Joan M Cook-Mills
- Allergy/Immunology Division, Northwestern University, 240 E Huron, Chicago, IL 60611, United States.
| | | | - Jan Frank
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70599 Stuttgart, Germany.
| | - Gabriele Cruciani
- Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy.
| | - Stefan Lorkowski
- Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 25, 07743 Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany.
| | - Nesrin Kartal Özer
- Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research Center (GEMHAM), Marmara University, 34854 Maltepe, Istanbul, Turkey.
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Hammann S, Kröpfl A, Vetter W. More than 170 polyunsaturated tocopherol-related compounds in a vitamin E capsule: Countercurrent chromatographic enrichment, gas chromatography/mass spectrometry analysis and preliminary identification of the potential artefacts. J Chromatogr A 2016; 1476:77-87. [DOI: 10.1016/j.chroma.2016.11.018] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 11/09/2016] [Accepted: 11/12/2016] [Indexed: 11/25/2022]
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Podszun MC, Jakobi M, Birringer M, Weiss J, Frank J. The long chain α-tocopherol metabolite α-13'-COOH and γ-tocotrienol induce P-glycoprotein expression and activity by activation of the pregnane X receptor in the intestinal cell line LS 180. Mol Nutr Food Res 2016; 61. [PMID: 27714977 DOI: 10.1002/mnfr.201600605] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Revised: 09/06/2016] [Accepted: 09/30/2016] [Indexed: 12/24/2022]
Abstract
SCOPE Members of the vitamin E family or their metabolites may induce the xenobiotic transporter P-glycoprotein (P-gp), which can limit the bioavailability of drugs and phytochemicals. This study aimed to investigate if α- and γ-tocopherol, α- and γ-tocotrienol, the long chain metabolite α-tocopherol-13'-COOH, the short chain metabolites α- and γ-carboxyethylhydroxychromanol and plastochromanol-8 activate the pregnane X receptor (PXR) and thereby modulate P-gp expression and/or activity. METHODS AND RESULTS P-gp protein expression and activity were studied in LS 180 cells incubated with the respective test compound for 48 h. Furthermore, we determined if the compounds activate PXR in LS 180 cells, as PXR regulates P-gp expression. Neither P-gp protein expression and activity, nor PXR activity were influenced by α-tocopherol, γ-tocopherol and plastochromanol-8. α-Tocotrienol activated PXR in the reporter gene assay but did not induce protein expression or activity of P-gp. γ-Tocotrienol and α-13'-COOH activated PXR and induced protein expression and transporter activity of P-gp. CONCLUSION Because the induction of P-gp in the intestine may limit the systemic bioavailability of its substrates, the concurrent intake of drugs and γ-tocotrienol and, if ever applicable, α-13'-COOH should be avoided.
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Affiliation(s)
- Maren C Podszun
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany
| | - Metta Jakobi
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany
| | - Marc Birringer
- Department of Nutritional, Food and Consumer, University of Applied Sciences, Fulda, Germany
| | - Johanna Weiss
- Department of Clinical Pharmacology and Pharmacoepidemiology, University Hospital Heidelberg, Germany
| | - Jan Frank
- Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany
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GC-MS and LC-MS approaches for determination of tocopherols and tocotrienols in biological and food matrices. J Pharm Biomed Anal 2016; 127:156-69. [PMID: 26964480 DOI: 10.1016/j.jpba.2016.02.051] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Revised: 02/17/2016] [Accepted: 02/28/2016] [Indexed: 11/20/2022]
Abstract
Tocopherols and tocotrienols, widely described as vitamin E derivatives, have been proven to take part in a number of important biological functions. Among them, antioxidant properties had been investigated and documented in the literature. Since tocochromanols have revealed their plausible beneficial impact on several pathological processes, such as cancerogenesis or cognitive impairment diseases, there is a growing interest in quantitative determination of these compounds in biological fluids, tissues and plant organs. However, due to vitamin E chemical features, such as lipophilic and non-polar characteristics, quantitative determination of the compounds seems to be problematic. In this paper we present current analytical approaches in tocopherols and tocotrienols determination in biological and food matrices with the use of chromatographic techniques, especially gas chromatography (GC) and high performance liquid chromatography (HPLC) coupled with mass spectrometry. Derivatization techniques applied for GC-MS analysis in the case of tocol derivatives, especially silylation and acylation, are described. Significant attention is paid to ionization process of tocopherols and tocotrienols.
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50
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Schmölz L, Birringer M, Lorkowski S, Wallert M. Complexity of vitamin E metabolism. World J Biol Chem 2016; 7:14-43. [PMID: 26981194 PMCID: PMC4768118 DOI: 10.4331/wjbc.v7.i1.14] [Citation(s) in RCA: 135] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 11/25/2015] [Accepted: 01/19/2016] [Indexed: 02/05/2023] Open
Abstract
Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their side-chain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a supplement or nutrient. To evaluate individual vitamin E status, the analytical procedures used for detecting and quantifying vitamin E and its metabolites are crucial. The latest methods in analytics are presented.
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