Dietary Antioxidants: Their Complex Interplay with Nutrients and Pharmaceuticals

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Natural and Synthetic Antioxidants".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 35440

Special Issue Editors


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Guest Editor
Institute of Nutritional Science, Friedrich Schiller University Jena, 07743 Jena, Germany
Interests: vitamins; inflammation; cardiometabolic diseases; skin diseases; macrophages
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Co-Guest Editor
Department of Nutritional, Food and Consumer Sciences, Fulda University of Applied Sciences, 36037 Fulda, Germany
Interests: oxidative stress; adaptive stress response; vitamins; nutrition; inflammation; natural products; antioxidants

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Institute of Nutritional Sciences and Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Friedrich Schiller University Jena, 07743 Jena, Germany
Interests: vitamin E in health and disease; cardiometabolic diseases; inflammation; vitamin E metabolism; long-chain metabolites of vitamin E
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antioxidants are ubiquitous in human nutrition and have the potential to act as nutraceuticals in the prevention or therapy of many chronic diseases driven by oxidative stress. Several micronutrients, namely vitamins and phytochemicals, express antioxidative capacities by regulating redox homeostasis and redox signalling. It is known that for specific populations the dietary intake of antioxidative vitamins, such as vitamins E, D and C, is insufficient. To compensate the dietary deficiencies supplementation with multivitamin complexes or phytochemicals is widely used, regardless of the lack of knowledge on the potential synergistic or antagonistic effects of dietary antioxidants with nutrients and pharmaceuticals. There are central questions of interest which have not been answered so far: In which cell compartment do the dietary antioxidants actually release their potential and affect oxidative processes? How are exogenous antioxidants transported to their place of action? Do they interfere with endogenous antioxidative systems? Which factors, i.e., nutrients and drugs, do interfere with the uptake, bioavailability, accumulation, circulation and excretion of dietary antioxidants in the human body?

To address these questions, the Special Issue "Dietary Antioxidants: their complex interplay with nutrients and pharmaceuticals" aims to collect reports and reviews investigating the underlying molecular mechanisms of the bioavailability of dietary antioxidants, as well as antioxidant-nutrient interactions, antioxidant-drug interactions, and interferences of antioxidants with human metabolism. Furthermore, studies focusing on the development of new experimental approaches, analytical methods and targeted delivery systems of dietary antioxidants will be welcome.

Dr. Maria Wallert
Guest Editor

Prof. Dr. Marc Birringer 
Prof. Dr. Stefan Lorkowski
Co-Guest Editors

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Keywords

  • bioavailability
  • antioxidant-nutrient interactions
  • antioxidant-drug interactions
  • interferences of antioxidants with metabolism

Published Papers (7 papers)

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Research

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16 pages, 2245 KiB  
Article
Improved Bioavailability and Bioaccessibility of Lutein and Isoflavones in Cultured Cells In Vitro through Interaction with Ginger, Curcuma and Black Pepper Extracts
by Bernhard Blank-Landeshammer, Gerald Klanert, Lisa Mitter, Sophia Turisser, Nicolas Nusser, Alice König, Marcus Iken and Julian Weghuber
Antioxidants 2022, 11(10), 1917; https://doi.org/10.3390/antiox11101917 - 27 Sep 2022
Cited by 5 | Viewed by 2223
Abstract
Intestinal absorption is intrinsically low for lipophilic micronutrients and phytochemicals. Plant extracts acting as bioavailability enhancers can complement for this deficiency by modulation of both, physicochemical and biochemical parameters, in the absorption process. However, these interactions often are limited to specific conditions and [...] Read more.
Intestinal absorption is intrinsically low for lipophilic micronutrients and phytochemicals. Plant extracts acting as bioavailability enhancers can complement for this deficiency by modulation of both, physicochemical and biochemical parameters, in the absorption process. However, these interactions often are limited to specific conditions and the mechanisms and potential synergisms are poorly understood. In this work, we used a human intestinal cell line to characterize the impact of extracts from C. longa (curcuma), Z. officinale (ginger) and P.nigrum (black pepper) on uptake and transport rates of the xanthophylls lutein and zeaxanthin as well as soy isoflavones measured by HPLC-DAD. We found a significant increase in the uptake of lutein in the presence of curcuma extract and enhanced isoflavone transport rates mediated by curcuma and ginger extracts. Combinations of the plant extracts did not lead to any additional increase in uptake or transport rates. By investigation of mixed micelle incorporation efficiency, we could dismiss changes in bioaccessibility as a potential enhancing mechanism in our experimental setup. We further conducted a rhodamine 123 efflux assay and discovered inhibition of P-glycoproteins by the ginger and black pepper extracts, highlighting a plausible route of action leading to increased isoflavone bioavailability. Full article
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14 pages, 2445 KiB  
Article
The Interplay of Ascorbic Acid with Quinones-Chelators—Influence on Lipid Peroxidation: Insight into Anticancer Activity
by Olga Yu. Selyutina, Polina A. Kononova, Vladimir E. Koshman, Lidiya G. Fedenok and Nikolay E. Polyakov
Antioxidants 2022, 11(2), 376; https://doi.org/10.3390/antiox11020376 - 13 Feb 2022
Cited by 10 | Viewed by 2521
Abstract
Ascorbic acid is a multifaceted compound that can perform both antioxidant and pro-oxidant activities in the redox reactions induced by transition metal ions, so its role in nature and especially in the human body is still the subject of debate. In the present [...] Read more.
Ascorbic acid is a multifaceted compound that can perform both antioxidant and pro-oxidant activities in the redox reactions induced by transition metal ions, so its role in nature and especially in the human body is still the subject of debate. In the present study, we have examined the influence of ascorbic acid on lipid peroxidation in a model system that mimics the cell membrane, namely micelles of linoleic acid (LA), induced by chelate complexes of iron and copper ions with quinone-chelator 2-phenyl-4-(butylamino)-naphtholquinoline-7,12-dione (Q1). This quinone effectively generates reactive oxygen species and semiquinone radicals inside cancer cells via a cycling redox reaction. Here it was demonstrated that in the absence of quinone-chelator ascorbic acid significantly accelerates the lipid peroxidation induced by both Fe(II) and Cu(II) ions. It has been shown also that Q1 chelate complexes with Fe(II) and Cu(II) ions are redox active in the LA micelles oxidation. No effect of ascorbate was detected on the reactivity of chelate complex with Fe(II) ions. On the other hand, ascorbate performs pro-oxidant activity in Q1-Cu(II) complex induced reaction. We can conclude that ascorbate-driven redox cycling of Q1 may promote its anti-tumor activity. Full article
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15 pages, 4315 KiB  
Article
Anti-Allergic Effects of Myrciaria dubia (Camu-Camu) Fruit Extract by Inhibiting Histamine H1 and H4 Receptors and Histidine Decarboxylase in RBL-2H3 Cells
by Nhung Quynh Do, Shengdao Zheng, Sarang Oh, Quynh T. N. Nguyen, Minzhe Fang, Minseon Kim, Junhui Choi, Myeong-Ju Kim, Jeehaeng Jeong and Tae-Hoo Yi
Antioxidants 2022, 11(1), 104; https://doi.org/10.3390/antiox11010104 - 31 Dec 2021
Cited by 8 | Viewed by 2961
Abstract
Although Myrciaria dubia (camu-camu) has been shown to exert anti-oxidant and anti-inflammatory effects in both in vitro and in vivo studies, its use in allergic responses has not been elucidated. In the present study, the anti-allergic effect of 70% ethanol camu-camu fruit extract [...] Read more.
Although Myrciaria dubia (camu-camu) has been shown to exert anti-oxidant and anti-inflammatory effects in both in vitro and in vivo studies, its use in allergic responses has not been elucidated. In the present study, the anti-allergic effect of 70% ethanol camu-camu fruit extract was tested on calcium ionophore (A23187)-induced allergies in RBL-2H3 cells. The RBL-2H3 cells were induced with 100 nM A23187 for 6 h, followed by a 1 h camu-camu fruit extract treatment. A23187 sanitization exacerbated mast cell degranulation; however, camu-camu fruit extract decreased the release of histamine and β-hexosaminidase, which are considered as key biomarkers in cell degranulation. Camu-camu fruit extract inhibited cell exocytosis by regulating the calcium/nuclear factor of activated T cell (NFAT) signaling. By downregulating the activation of mitogen-activated protein kinase (MAPK) signaling, camu-camu fruit extract hindered the activation of both histamine H1 and H4 receptors and inhibited histidine decarboxylase (HDC) expression by mediating its transcription factors KLF4/SP1 and GATA2/MITF. In A23187-induced ROS overproduction, camu-camu fruit extract activated nuclear factor erythroid-2-related factor 2 (Nrf2) to protect mast cells against A23187-induced oxidative stress. These findings indicate that camu-camu fruit extract can be developed to act as a mast cell stabilizer and an anti-histamine. This work also “opens the door” to new investigations using natural products to achieve breakthroughs in allergic disorder treatment. Full article
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13 pages, 2037 KiB  
Article
The Inhibitory Activity of Curcumin on P-Glycoprotein and Its Uptake by and Efflux from LS180 Cells Is Not Affected by Its Galenic Formulation
by Sandra Flory, Romina Männle and Jan Frank
Antioxidants 2021, 10(11), 1826; https://doi.org/10.3390/antiox10111826 - 17 Nov 2021
Cited by 7 | Viewed by 2659
Abstract
The biological activities of curcumin in humans, including its antioxidative and anti-inflammatory functions, are limited by its naturally low bioavailability. Different formulation strategies have been developed, but the uptake of curcumin from these galenic formulations into and efflux from intestinal cells, which may [...] Read more.
The biological activities of curcumin in humans, including its antioxidative and anti-inflammatory functions, are limited by its naturally low bioavailability. Different formulation strategies have been developed, but the uptake of curcumin from these galenic formulations into and efflux from intestinal cells, which may be critical processes limiting bioavailability, have not been directly compared. Furthermore, little is known about their effect on P-glycoprotein activity, an important determinant of the pharmacokinetics of potentially co-administered drugs. P-glycoprotein activity was determined in LS180 cells, incubated with 30 or 60 µmol/L of curcumin in the form of seven different formulations or native curcuma extract for 1 h. All formulations inhibited P-glycoprotein activity at both concentrations. Curcumin uptake, after 1 h incubation of LS180 cells with the formulations (60 µmol/L), showed significant variability but no consistent effects. After 1 h pre-treatment with the formulations and further 8 h with curcumin-free medium, curcumin in cell culture supernatants, reflecting the efflux, differed between individual formulations, again without a clear effect. In conclusion, curcumin inhibits P-glycoprotein activity independently of its formulation. Its uptake by and efflux from intestinal cells was not significantly different between formulations, indicating that these processes are not important regulatory points for its bioavailability. Full article
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Review

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31 pages, 1711 KiB  
Review
Vitamin E and Metabolic Health: Relevance of Interactions with Other Micronutrients
by Sijia Liao, Sylvia Oghogho Omage, Lisa Börmel, Stefan Kluge, Martin Schubert, Maria Wallert and Stefan Lorkowski
Antioxidants 2022, 11(9), 1785; https://doi.org/10.3390/antiox11091785 - 9 Sep 2022
Cited by 20 | Viewed by 10377
Abstract
A hundred years have passed since vitamin E was identified as an essential micronutrient for mammals. Since then, many biological functions of vitamin E have been unraveled in both cell and animal models, including antioxidant and anti-inflammatory properties, as well as regulatory activities [...] Read more.
A hundred years have passed since vitamin E was identified as an essential micronutrient for mammals. Since then, many biological functions of vitamin E have been unraveled in both cell and animal models, including antioxidant and anti-inflammatory properties, as well as regulatory activities on cell signaling and gene expression. However, the bioavailability and physiological functions of vitamin E have been considerably shown to depend on lifestyle, genetic factors, and individual health conditions. Another important facet that has been considered less so far is the endogenous interaction with other nutrients. Accumulating evidence indicates that the interaction between vitamin E and other nutrients, especially those that are enriched by supplementation in humans, may explain at least some of the discrepancies observed in clinical trials. Meanwhile, increasing evidence suggests that the different forms of vitamin E metabolites and derivates also exhibit physiological activities, which are more potent and mediated via different pathways compared to the respective vitamin E precursors. In this review, possible molecular mechanisms between vitamin E and other nutritional factors are discussed and their potential impact on physiological and pathophysiological processes is evaluated using published co-supplementation studies. Full article
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21 pages, 1600 KiB  
Review
Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk
by Mackenzie Newman, Heather Connery and Jonathan Boyd
Antioxidants 2022, 11(7), 1267; https://doi.org/10.3390/antiox11071267 - 27 Jun 2022
Cited by 5 | Viewed by 5655
Abstract
Opioids are among the most widely used classes of pharmacologically active compounds both clinically and recreationally. Beyond their analgesic efficacy via μ opioid receptor (MOR) agonism, a prominent side effect is central respiratory depression, leading to systemic hypoxia and free radical generation. Vitamin [...] Read more.
Opioids are among the most widely used classes of pharmacologically active compounds both clinically and recreationally. Beyond their analgesic efficacy via μ opioid receptor (MOR) agonism, a prominent side effect is central respiratory depression, leading to systemic hypoxia and free radical generation. Vitamin C (ascorbic acid; AA) is an essential antioxidant vitamin and is involved in the recycling of redox cofactors associated with inflammation. While AA has been shown to reduce some of the negative side effects of opioids, the underlying mechanisms have not been explored. The present review seeks to provide a signaling framework under which MOR activation and AA may interact. AA can directly quench reactive oxygen and nitrogen species induced by opioids, yet this activity alone does not sufficiently describe observations. Downstream of MOR activation, confounding effects from AA with STAT3, HIF1α, and NF-κB have the potential to block production of antioxidant proteins such as nitric oxide synthase and superoxide dismutase. Further mechanistic research is necessary to understand the underlying signaling crosstalk of MOR activation and AA in the amelioration of the negative, potentially fatal side effects of opioids. Full article
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Other

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35 pages, 957 KiB  
Systematic Review
The Self-Administered Use of Complementary and Alternative Medicine (CAM) Supplements and Antioxidants in Cancer Therapy and the Critical Role of Nrf-2—A Systematic Review
by Paula Krejbich and Marc Birringer
Antioxidants 2022, 11(11), 2149; https://doi.org/10.3390/antiox11112149 - 30 Oct 2022
Cited by 6 | Viewed by 7404
Abstract
Complementary and alternative medicine (CAM) supplements are widely used by cancer patients. Dietary supplements, vitamins and minerals, herbal remedies, and antioxidants are especially popular. In a systematic literature review, 37 studies, each including more than 1000 participants, on CAM, dietary supplement, and vitamin [...] Read more.
Complementary and alternative medicine (CAM) supplements are widely used by cancer patients. Dietary supplements, vitamins and minerals, herbal remedies, and antioxidants are especially popular. In a systematic literature review, 37 studies, each including more than 1000 participants, on CAM, dietary supplement, and vitamin use among cancer patients were identified. Accordingly, cancer patients use antioxidants such as vitamin C (from 2.6% (United Kingdom) to 41.6% (United States)) and vitamin E (from 2.9% (China) to 48% (United States)). Dietary supplements and vitamins are taken for different reasons, but often during conventional cancer treatment involving chemotherapy or radiotherapy and in a self-decided manner without seeking medical advice from healthcare professionals. Drug–drug interactions with dietary supplements or vitamins involving multiple signaling pathways are well described. Since most of the anticancer drugs generate reactive oxygen species (ROS), an adaptive stress response of healthy and malignant cells, mainly driven by the Nrf-2-Keap I network, can be observed. On the one hand, healthy cells should be protected from ROS-overproducing chemotherapy and radiotherapy; on the other hand, ROS production in cancer cells is a “desirable side effect” during anticancer drug treatment. We here describe the paradoxical use of antioxidants and supplements during cancer therapy, possible interactions with anticancer drugs, and the involvement of the Nrf-2 transcription factor. Full article
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