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Antioxidants
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The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease
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The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (30 March 2022) | Viewed by 830489

Special Issue Editors

Dr. Sergio Davinelli

E-Mail Website
Guest Editor
Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
Interests: nutrition and dietetics; health promotion; aging; functional foods; food phytochemicals; dietary polyphenols
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Giovanni Scapagnini

E-Mail Website
Guest Editor
Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
Interests: phytochemicals; dietary supplementation; nutrition; natural compounds; antioxidants; aging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dietary phytochemicals comprise a large family of plant-derived metabolites with highly diverse chemical structures. These compounds are synthesized to increase the survival fitness of the plant by allowing it to interact with its environment. Population studies have shown that increased consumption of phytochemicals from fruits and vegetables is linked to a reduced risk of chronic diseases. The protective mechanisms involved in the bioactivity of dietary phytochemicals are still under active investigation. However, it is unlikely that they act as simple antioxidants that directly neutralize free radicals in vivo. A significant amount of scientific literature shows that dietary phytochemicals or their gut-derived metabolites act as signaling molecules, modulating one or more cellular pathways associated with disease prevention. Moreover, molecular docking studies have demonstrated that dietary phytochemicals can be accommodated in specific binding sites in the proximity of the active site, and the interaction with several cell components was monitored in situ. Finally, the excellent safety profile and large structural diversity make dietary phytochemicals particularly attractive for drug discovery processes.

This Special Issue will collect publications on topics including (but not limited to):

  • Biological effects associated with disease-prevention pathways;
  • Molecular pharmacology techniques to identify potential targets;
  • Phytochemical content of fruits and vegetables (e.g., variability, methods to estimate phytochemical content);
  • Bioavailability of dietary phytochemicals (e.g., gut microbiota, culinary techniques, additive/synergistic effects);
  • Dietary phytochemicals and the design of new drugs/supplements to target disease-prevention mechanisms;
  • Dietary phytochemicals and human intervention trials;
  • Dietary phytochemicals from an epidemiological perspective.
Dr. Sergio Davinelli
Prof. Dr. Giovanni Scapagnini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • phytochemicals 
  • plant-based diets 
  • prevention 
  • pharma-nutrition 
  • drug discovery

Published Papers (16 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 204 KiB  
Editorial
The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease
by Sergio Davinelli and Giovanni Scapagnini
Antioxidants 2022, 11(6), 1081; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11061081 - 29 May 2022
Cited by 3 | Viewed by 1569
Abstract
There is an increasing number of disease areas where nutritional and pharmacological applications complement each other [...] Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)

Research

Jump to: Editorial, Review, Other

17 pages, 4774 KiB  
Article
Modulating the Growth, Antioxidant Activity, and Immunoexpression of Proinflammatory Cytokines and Apoptotic Proteins in Broiler Chickens by Adding Dietary Spirulina platensis Phycocyanin
by Anaam E. Omar, Hanan S. Al-Khalaifah, Ali Osman, Ahmed Gouda, Shimaa I. Shalaby, Elshimaa M. Roushdy, Samar A. Abdo, Sozan A. Ali, Aziza M. Hassan and Shimaa A. Amer
Antioxidants 2022, 11(5), 991; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11050991 - 19 May 2022
Cited by 23 | Viewed by 2571
Abstract
This study investigated the dietary effect of Spirulina platensis phycocyanin (SPC) on growth performance (body weight (BW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR)) at starter, grower, and finisher stages, intestinal histomorphology, serum biochemical parameters, inflammatory and antioxidant indices, [...] Read more.
This study investigated the dietary effect of Spirulina platensis phycocyanin (SPC) on growth performance (body weight (BW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR)) at starter, grower, and finisher stages, intestinal histomorphology, serum biochemical parameters, inflammatory and antioxidant indices, and proinflammatory cytokines (tumor necrosis factor-α and caspase-3) immune expression in broiler chickens. In total, 250 one-day-old chicks (Ross 308 broiler) were randomly allotted to five experimental groups (5 replicates/group, 10 chicks/replicate) and fed basal diets supplemented with five levels of SPC (0, 0.25, 0.5, 0.75, and 1 g kg–1 diet) for 35 days. Compared with SPC0 treatment, different SPC levels increased the overall BW and BWG without affecting the total feed consumption. However, the FCR decreased linearly with an increase in supplementation level. The serum levels of total proteins, albumin, globulins, and growth hormone increased linearly by increasing levels of SPC supplementation. Further, SPC supplementation increased the thyroxin hormones without affecting serum glucose and leptin levels. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) values decreased in broilers fed SPC0.250 and SPC1 diets. Triglycerides (TG) decreased in SPC0.25-, SPC0.75-, and SPC1-treated groups. Though antioxidant enzyme activities (total antioxidant capacity, catalase, and superoxide dismutase) increased linearly and quadratically, malondialdehyde (MDA) decreased linearly by increasing the SPC level. There was no effect on serum proinflammatory cytokines IL1β levels. Immunolabelling index of caspase-3 and tumor necrosis factor-α (TNF-α) were downregulated by SPC supplementation. The intestinal histomorphology is represented by increased villus height, the villus height to crypt depth ratio, and numbers of goblet cells in different sections of the small intestine. In conclusion, SPC supplementation is beneficial in broiler chicken diets due to its growth-promoting, antioxidant, and anti-inflammatory properties. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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14 pages, 2281 KiB  
Article
Resveratrol Butyrate Ester Protects Adenine-Treated Rats against Hypertension and Kidney Disease by Regulating the Gut–Kidney Axis
by Chien-Ning Hsu, Chih-Yao Hou, Chi-I Chang and You-Lin Tain
Antioxidants 2022, 11(1), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010083 - 29 Dec 2021
Cited by 16 | Viewed by 2499
Abstract
Despite recent advances in pharma-nutritional management, chronic kidney disease (CKD) remains an increasingly prevalent disorder. Resveratrol, a pleiotropic phytochemical, has been found to reduce the risk for several chronic diseases. Considering the low bioavailability of resveratrol, we recently synthesized resveratrol butyrate ester (RBE) [...] Read more.
Despite recent advances in pharma-nutritional management, chronic kidney disease (CKD) remains an increasingly prevalent disorder. Resveratrol, a pleiotropic phytochemical, has been found to reduce the risk for several chronic diseases. Considering the low bioavailability of resveratrol, we recently synthesized resveratrol butyrate ester (RBE) via the esterification of resveratrol with butyrate. The aim of this study was to examine the effectiveness of RBE as regards protection from hypertension and kidney damage and explore the underlying mechanisms using a young rat adenine-induced CKD model. Three-week-old male Sprague Dawley rats received regular or 0.5% adenine chow for three weeks. Three groups of adenine-fed CKD rats (N = 8/group) received resveratrol (50 mg/L), or a low dose (25 mg/L) or high dose (50 mg/L) of RBE in drinking water from week 6 to week 12. As compared with the controls, adenine-treated rats had markedly increased creatinine levels and blood pressure, which was associated with renal hypertrophy and decreased creatinine clearance. Treatment with resveratrol or a low or high dose of RBE, similarly protected adenine-fed rats against hypertension and kidney damage. CKD-induced hypertension is associated with an altered gut microbiota profile, dysregulated renal short chain fatty acid (SCFA) receptor expression, activation of the aryl hydrocarbon receptor (AhR) signaling pathway, and reduced nitric oxide bioavailability. We found gut microbiota compositions were shaped differentially by resveratrol and RBE treatment in adenine-treated CKD rats. The beneficial effect of high-dose RBE was associated with reduced renal expression of SCFA G protein-coupled receptor 41 (GPR41) and olfactory receptor 78 (Olfr78), antagonizing the AhR signaling pathway, and increased abundance of beneficial bacteria such as genera Akkermansia, Blautia, and Enterococcus. Our study provided the first evidence documenting RBE as a novel phytochemical supplement targeting the gut–kidney axis to protect against adenine-induced kidney damage and hypertension. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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14 pages, 733 KiB  
Article
Comprehensive Biological and Chemical Evaluation of Two Seseli Species (S. gummiferum and S. transcaucasicum)
by Gokhan Zengin, Dejan Stojković, Mohamad Fawzi Mahomoodally, Bibi Sharmeen Jugreet, Mehmet Yavuz Paksoy, Marija Ivanov, Uroš Gašić, Monica Gallo and Domenico Montesano
Antioxidants 2021, 10(10), 1510; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10101510 - 24 Sep 2021
Cited by 6 | Viewed by 2292
Abstract
Seseli L. is one of the largest genera of the Apiaceae family widely known for their traditional uses as herbal remedies. In the present study, the methanolic and water extracts of two Seseli species, S. gummiferum and S. transcaucasicum were evaluated for their [...] Read more.
Seseli L. is one of the largest genera of the Apiaceae family widely known for their traditional uses as herbal remedies. In the present study, the methanolic and water extracts of two Seseli species, S. gummiferum and S. transcaucasicum were evaluated for their bioactive contents and biological activities. The total phenolic and flavonoid contents in the extracts ranged from 19.09 to 24.33 mg GAE/g and from 0.45 to10.09 mg RE/g, respectively. Moreover, while narcissin was detected as the most abundant component in the methanolic extract of S. transcaucasicum (261.40 µg/g), chlorogenic acid was identified as the major component in all the other extracts, although a high amount was also present in the methanolic S. transcaucasicum extract (107.48–243.12 µg/g). The total antioxidant capacity was also determined by the phosphomolybdenum assay (0.66–1.18 mM TE/g). Other antioxidant assays such as the radical scavenging assays (DPPH: 5.51–11.45 mg TE/g; ABTS: 43.46–51.91 mg TE/g), reducing assays (CUPRAC: 41.67–53.20 mg TE/g; FRAP: 31.26–34.14 mg TE/g), as well as the metal chelating activity assay (14.38–38.57 mg EDTAE/g) were conducted. All the extracts showed inhibitory potential against the enzyme’s amylase (0.12–0.78 mM ACAE/g), acetyl- and butyryl-cholinesterase (0.15–9.71 mg GALAE/g), while only the methanolic extracts acted as inhibitors of tyrosinase (107.15 and 109.37 mg KAE/g) and only the water extract of S. gummiferum displayed anti-glucosidase activity (0.13 mM ACAE/g). Interestingly, the methanolic extracts of both Seseli species showed lower cytotoxicity towards HaCaT cells (IC50: >500 µg/mL), compared to the water extracts (IC50: 267.8 and 321.41 µg/mL). Besides, only the methanolic extracts showed a slight wound healing effect (28.21 and 31.23%). All extracts showed antibacterial action against Staphylococcus lugdunensis (minimum inhibitory and bactericidal concentrations: 0.025–2 mg/mL). S. gummiferum methanolic extract, which exhibited the highest antibacterial potency was found to inhibit adhesion and invasion of S. lugdunensis to HaCaT cells as well. Taken together, this study demonstrated the two Seseli species to harbour interesting bioactive components, in particular polyphenolics and to exhibit several biological properties that could be further investigated for their potential exploitation as healing agents as supported by various traditional medicinal uses. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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17 pages, 1809 KiB  
Article
Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells
by Sadaf Harandi-Zadeh, Cayla Boycott, Megan Beetch, Tony Yang, Benjamin J. E. Martin, Kevin Ren, Anna Kwasniak, John H. Dupuis, Katarzyna Lubecka, Rickey Y. Yada, LeAnn J. Howe and Barbara Stefanska
Antioxidants 2021, 10(8), 1232; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10081232 - 30 Jul 2021
Cited by 7 | Viewed by 2443
Abstract
Epigenetic aberrations are linked to sporadic breast cancer. Interestingly, certain dietary polyphenols with anti-cancer effects, such as pterostilbene (PTS), have been shown to regulate gene expression by altering epigenetic patterns. Our group has proposed the involvement of DNA methylation and DNA methyltransferase 3B [...] Read more.
Epigenetic aberrations are linked to sporadic breast cancer. Interestingly, certain dietary polyphenols with anti-cancer effects, such as pterostilbene (PTS), have been shown to regulate gene expression by altering epigenetic patterns. Our group has proposed the involvement of DNA methylation and DNA methyltransferase 3B (DNMT3B) as vital players in PTS-mediated suppression of candidate oncogenes and suggested a role of enhancers as target regions. In the present study, we assess a genome-wide impact of PTS on epigenetic marks at enhancers in highly invasive MCF10CA1a breast cancer cells. Following chromatin immunoprecipitation (ChIP)-sequencing in MCF10CA1a cells treated with 7 μM PTS for 9 days, we discovered that PTS leads to increased binding of DNMT3B at enhancers of 77 genes, and 17 of those genes display an overlapping decrease in the occupancy of trimethylation at lysine 36 of histone 3 (H3K36me3), a mark of active enhancers. We selected two genes, PITPNC1 and LINC00910, and found that their enhancers are hypermethylated in response to PTS. These changes coincided with the downregulation of gene expression. Of importance, we showed that 6 out of 17 target enhancers, including PITPNC1 and LINC00910, are bound by an oncogenic transcription factor OCT1 in MCF10CA1a cells. Indeed, the six enhancers corresponded to genes with established or putative cancer-driving functions. PTS led to a decrease in OCT1 binding at those enhancers, and OCT1 depletion resulted in PITPNC1 and LINC00910 downregulation, further demonstrating a role for OCT1 in transcriptional regulation. Our findings provide novel evidence for the epigenetic regulation of enhancer regions by dietary polyphenols in breast cancer cells. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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14 pages, 2727 KiB  
Article
Anti-Inflammatory and Anti-Hyperuricemic Effects of Chrysin on a High Fructose Corn Syrup-Induced Hyperuricemia Rat Model via the Amelioration of Urate Transporters and Inhibition of NLRP3 Inflammasome Signaling Pathway
by Yi-Hsien Chang, Yi-Fen Chiang, Hsin-Yuan Chen, Yun-Ju Huang, Kai-Lee Wang, Yong-Han Hong, Mohamed Ali, Tzong-Ming Shieh and Shih-Min Hsia
Antioxidants 2021, 10(4), 564; https://doi.org/10.3390/antiox10040564 - 06 Apr 2021
Cited by 35 | Viewed by 4954
Abstract
Hyperuricemia is the main cause of gout and involved in the occurrence of many other diseases such as hyperlipidemia and hypertension correlated with metabolic disorders. Chrysin is a flavonoid compound found naturally in honey, propolis, and mushrooms and has anti-inflammatory and antioxidant effects. [...] Read more.
Hyperuricemia is the main cause of gout and involved in the occurrence of many other diseases such as hyperlipidemia and hypertension correlated with metabolic disorders. Chrysin is a flavonoid compound found naturally in honey, propolis, and mushrooms and has anti-inflammatory and antioxidant effects. However, its mechanism of action is not clear yet. This study investigated the mechanism of chrysin’s anti-hyperuricemic effect in hyperuricemia-induced rats fed with high-fructose corn syrup. Orally administrated chrysin for 28 consecutive days effectively decreased uric acid by inhibiting the activity of xanthine oxidase (XO) in the liver. Moreover, chrysin markedly downregulated the protein expression of uric acid transporter 1 (URAT1) and glucose transporter type 9 (GLUT9) and upregulated the protein expression of organic anion transporter 1 (OAT1) and human ATP-binding cassette subfamily G-2 (ABCG2). In addition, chrysin showed prominent anti-oxidative and inflammatory effects as the malondialdehyde (MDA) and interleukin 1 beta (IL-1β) concentration was reduced in both rat kidney and serum, which aligned with the inhibition of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway activation. Collectively, our results strongly suggest that chrysin exhibits potent anti-hyperuricemic and anti-inflammatory effects that may yield new adjuvant treatments for gout. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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Graphical abstract

14 pages, 6912 KiB  
Article
Raspberry Ketones Attenuate Cyclophosphamide-Induced Pulmonary Toxicity in Mice through Inhibition of Oxidative Stress and NF-ΚB Pathway
by Marwa T. Mohamed, Sawsan A. Zaitone, Amal Ahmed, Eman T. Mehanna and Norhan M. El-Sayed
Antioxidants 2020, 9(11), 1168; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9111168 - 23 Nov 2020
Cited by 10 | Viewed by 2958
Abstract
Cyclophosphamide (CP) was found to have a potential toxic effect on lung tissues. Raspberry ketones (RKs) are natural antioxidant chemicals isolated from red raspberries (Rubus ideaus). They are commonly used for weight loss and obesity. The current study aimed to evaluate the possible [...] Read more.
Cyclophosphamide (CP) was found to have a potential toxic effect on lung tissues. Raspberry ketones (RKs) are natural antioxidant chemicals isolated from red raspberries (Rubus ideaus). They are commonly used for weight loss and obesity. The current study aimed to evaluate the possible protective effects of RKs against lung toxicity induced by CP. Mice were allocated into six groups: (1) control group; (2) CP group: received a single intraperitoneal dose of CP (150 mg/kg, i.p.); and (3–6) mice were pre-treated orally with different doses of RKs (25, 50, 100, and 200 mg/kg) for 14 consecutive days, respectively, before the administration of an intraperitoneal dose of CP (150 mg/kg, i.p.). Mice were then sacrificed under anesthesia, then lungs were removed for histopathological and biochemical investigations. A single dose of CP markedly altered the levels of some oxidative stress biomarkers and resulted in the fragmentation of DNA in lung homogenates. Histological examination of CP-treated mice demonstrated diffuse alveolar damage that involved apparent hyalinization of membranes, thickening of inter alveolar septa, and proliferation of type II pneumocytes. The immunohistochemical results of CP-treated mice revealed strongly positive Bax and weakly positive proliferating cell nuclear antigen (PCNA) staining reactivity of the nuclei of the lining epithelium of the bronchioles and alveoli. CP activated the cyclooxygenase-2/nuclear factor-kappa B pathway. However, pre-treatment with RKs significantly attenuated CP-evoked alterations in the previously mentioned parameters, highlighting their antioxidant, anti-inflammatory, and anti-apoptotic potential. RKs may be suggested to be a potential candidate to ameliorate CP-induced pulmonary toxicity. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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20 pages, 10864 KiB  
Article
Natural Antioxidant Control of Neuropathic Pain—Exploring the Role of Mitochondrial SIRT3 Pathway
by Sara Ilari, Luigino Antonio Giancotti, Filomena Lauro, Micaela Gliozzi, Valentina Malafoglia, Ernesto Palma, Marco Tafani, Matteo Antonio Russo, Carlo Tomino, Massimo Fini, Daniela Salvemini, Vincenzo Mollace and Carolina Muscoli
Antioxidants 2020, 9(11), 1103; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9111103 - 09 Nov 2020
Cited by 31 | Viewed by 3091
Abstract
Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and [...] Read more.
Neuropathic pain is a chronic painful disease. Data have shown that reactive oxygen species (ROS) are implicated in chronic pain. Particularly, the enhanced ROS production alters the mitochondrial genome and proteome through the accumulation of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA). Sirtuin 3 (SIRT3) is a mitochondrial protein and its activity can reduce ROS levels by modulating key antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Here, we evaluated the role of SIRT3 in the maintenance of basal levels of ROS in a model of chronic constriction injury (CCI) of the sciatic nerve and the protective effects of a natural antioxidant, the bergamot polyphenolic fraction (BPF). Rats were exposed to CCI of the sciatic nerve in the presence or absence of BPF (25–75 mg/kg). Level of acetylation, post-translational modulation on cysteine residues of proteins by HNE and SIRT3 activation, were detected in the spinal cord through western blotting, WES methodology and enzymatic assays. Our results reported that SIRT3 carbonylation and therefore its inactivation contributes to mitochondrial MnSOD hyperacetylation during CCI induced neuropathic pain in rats. In particular, we have demonstrated a close relation between oxidative stress, hyperalgesia, allodynia and sirtuins inactivation reverted by BPF administration. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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13 pages, 258 KiB  
Article
Total Dietary Antioxidant Capacity and Longitudinal Trajectories of Body Composition
by Niels van der Schaft, Katerina Trajanoska, Fernando Rivadeneira, M. Arfan Ikram, Josje D. Schoufour and Trudy Voortman
Antioxidants 2020, 9(8), 728; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9080728 - 10 Aug 2020
Cited by 4 | Viewed by 2563
Abstract
Although there is some evidence that total dietary antioxidant capacity (TDAC) is inversely associated with the presence of obesity, no longitudinal studies have been performed investigating the effect of TDAC on comprehensive measures of body composition over time. In this study, we included [...] Read more.
Although there is some evidence that total dietary antioxidant capacity (TDAC) is inversely associated with the presence of obesity, no longitudinal studies have been performed investigating the effect of TDAC on comprehensive measures of body composition over time. In this study, we included 4595 middle-aged and elderly participants from the Rotterdam Study, a population-based cohort. We estimated TDAC among these individuals by calculating a ferric reducing ability of plasma (FRAP) score based on data from food-frequency questionnaires. Body composition was assessed by means of dual X-ray absorptiometry at baseline and every subsequent 3–5 years. From these data, we calculated fat mass index (FMI), fat-free mass index (FFMI), android-to-gynoid fat ratio (AGR), body fat percentage (BF%) and body mass index (BMI). We also assessed hand grip strength at two time points and prevalence of sarcopenia at one time point in a subset of participants. Data were analyzed using linear mixed models or multinomial logistic regression models with multivariable adjustment. We found that higher FRAP score was associated with higher FFMI (0.091 kg/m2 per standard deviation (SD) higher FRAP score, 95% CI 0.031; 0.150), lower AGR (−0.028, 95% CI −0.053; −0.003), higher BMI (0.115, 95% CI 0.020; 0.209) and lower BF% (−0.223, 95% CI −0.383; −0.064) across follow-up after multivariable adjustment. FRAP score was not associated with hand grip strength or sarcopenia. Additional adjustment for adherence to dietary guidelines and exclusion of individuals with comorbid disease at baseline did not change our results. In conclusion, dietary intake of antioxidants may positively affect the amount of lean mass and overall body composition among the middle-aged and elderly. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)

Review

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48 pages, 1442 KiB  
Review
Dietary Phytoestrogens and Their Metabolites as Epigenetic Modulators with Impact on Human Health
by Victor Stefan Ionescu, Alexandra Popa, Andrei Alexandru, Emilia Manole, Mihaela Neagu and Sevinci Pop
Antioxidants 2021, 10(12), 1893; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10121893 - 26 Nov 2021
Cited by 21 | Viewed by 4099
Abstract
The impact of dietary phytoestrogens on human health has been a topic of continuous debate since their discovery. Nowadays, based on their presumptive beneficial effects, the amount of phytoestrogens consumed in the daily diet has increased considerably worldwide. Thus, there is a growing [...] Read more.
The impact of dietary phytoestrogens on human health has been a topic of continuous debate since their discovery. Nowadays, based on their presumptive beneficial effects, the amount of phytoestrogens consumed in the daily diet has increased considerably worldwide. Thus, there is a growing need for scientific data regarding their mode of action in the human body. Recently, new insights of phytoestrogens’ bioavailability and metabolism have demonstrated an inter-and intra-population heterogeneity of final metabolites’ production. In addition, the phytoestrogens may have the ability to modulate epigenetic mechanisms that control gene expression. This review highlights the complexity and particularity of the metabolism of each class of phytoestrogens, pointing out the diversity of their bioactive gut metabolites. Futhermore, it presents emerging scientific data which suggest that, among well-known genistein and resveratrol, other phytoestrogens and their gut metabolites can act as epigenetic modulators with a possible impact on human health. The interconnection of dietary phytoestrogens’ consumption with gut microbiota composition, epigenome and related preventive mechanisms is discussed. The current challenges and future perspectives in designing relevant research directions to explore the potential health benefits of dietary phytoestrogens are also explored. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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13 pages, 2320 KiB  
Review
Carotenoids and Cognitive Outcomes: A Meta-Analysis of Randomized Intervention Trials
by Sergio Davinelli, Sawan Ali, Vincenzo Solfrizzi, Giovanni Scapagnini and Graziamaria Corbi
Antioxidants 2021, 10(2), 223; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10020223 - 02 Feb 2021
Cited by 35 | Viewed by 3949
Abstract
Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation of cognitive function. A meta-analysis of randomized controlled [...] Read more.
Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation of cognitive function. A meta-analysis of randomized controlled trials was conducted to examine the relationship between carotenoid supplementation and cognitive performance. A literature search was conducted in the MEDLINE (via PubMed), Scopus, Web of Science, and Cochrane databases from their inception to July 2020. A total of 435 studies were retrieved. Abstract screening using predefined inclusion and exclusion criteria was followed by full-text screening and data extraction of study characteristics and measured outcomes. A meta-analysis of eligible trials was performed using a random-effects model to estimate pooled effect size. We identified 9 studies with a total of 4402 nondemented subjects, whose age ranged from 45 to 78 years. Results of the pooled meta-analysis found a significant effect of carotenoid intervention on cognitive outcomes (Hedge’s g = 0.14; 95% confidence interval: 0.08, 0.20, p < 0.0001). There was no evidence of heterogeneity among the studies (τ2 = 0.00, I2 = 0.00%, H2 = 1.00) or publication bias. Although further studies are needed, our results suggest that carotenoid interventions are associated with better cognitive performance. Thus, these dietary compounds may help to reduce the risk of cognitive impairment and dementia. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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21 pages, 7590 KiB  
Review
Hypoglycemic Effect of Resveratrol: A Systematic Review and Meta-Analysis
by Beatriz Isabel García-Martínez, Mirna Ruiz-Ramos, José Pedraza-Chaverri, Edelmiro Santiago-Osorio and Víctor Manuel Mendoza-Núñez
Antioxidants 2021, 10(1), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10010069 - 07 Jan 2021
Cited by 16 | Viewed by 3950
Abstract
Resveratrol (RV) is a polyphenolic compound with antioxidant, anti-inflammatory, and hypoglycemic properties. Several in vitro and animal model studies have demonstrated the beneficial effects of RV; however, the results in humans are not conclusive. After a search of different databases, 32 studies were [...] Read more.
Resveratrol (RV) is a polyphenolic compound with antioxidant, anti-inflammatory, and hypoglycemic properties. Several in vitro and animal model studies have demonstrated the beneficial effects of RV; however, the results in humans are not conclusive. After a search of different databases, 32 studies were selected for this systematic review and 30 were included in the meta-analysis. Studies that evaluated the effect of RV on glucose, insulin, HbA1c, and insulin resistance (HOMA-IR) levels were included. A significant decrease of glucose (−5.24 mg/dL, p = 0.002) and insulin levels (−1.23 mIU/L, p = 0.0003) was observed. HbA1c and HOMA-IR did not show significant changes. Due to heterogeneity, sub-analyzes were performed. Sub-analysis by dose revealed that glucose levels improve significantly after the administration of 500–1000 mg/day of RV (−7.54 mg/dL, p = 0.002), while insulin improves with doses lower than 500 mg/day (−1.43 mIU/L, p = 0.01) and greater than 1000 mg/day (−2.12 mIU/L, p = 0.03). HbA1c and HOMA-IR remained unchanged after sub-analysis by dose. Our findings suggest that RV improves glucose and insulin levels in subjects with type 2 diabetes mellitus (T2DM) and aged 45–59 years, regardless of the duration of the intervention. HbA1c improves with interventions ≥3 months. HOMA-IR does not exhibit significant changes after RV administration. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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17 pages, 1404 KiB  
Review
Tackling Chronic Inflammation with Withanolide Phytochemicals—A Withaferin A Perspective
by Emilie Logie and Wim Vanden Berghe
Antioxidants 2020, 9(11), 1107; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9111107 - 10 Nov 2020
Cited by 32 | Viewed by 3879
Abstract
Chronic inflammatory diseases are considered to be one of the biggest threats to human health. Most prescribed pharmaceutical drugs aiming to treat these diseases are characterized by side-effects and negatively affect therapy adherence. Finding alternative treatment strategies to tackle chronic inflammation has therefore [...] Read more.
Chronic inflammatory diseases are considered to be one of the biggest threats to human health. Most prescribed pharmaceutical drugs aiming to treat these diseases are characterized by side-effects and negatively affect therapy adherence. Finding alternative treatment strategies to tackle chronic inflammation has therefore been gaining interest over the last few decades. In this context, Withaferin A (WA), a natural bioactive compound isolated from Withania somnifera, has been identified as a promising anti-cancer and anti-inflammatory compound. Although the majority of studies focus on the molecular mechanisms of WA in cancer models, recent evidence demonstrates that WA also holds promise as a new phytotherapeutic agent against chronic inflammatory diseases. By targeting crucial inflammatory pathways, including nuclear factor kappa B (NF-κB) and nuclear factor erythroid 2 related factor 2 (Nrf2) signaling, WA suppresses the inflammatory disease state in several in vitro and preclinical in vivo models of diabetes, obesity, neurodegenerative disorders, cystic fibrosis and osteoarthritis. This review provides a concise overview of the molecular mechanisms by which WA orchestrates its anti-inflammatory effects to restore immune homeostasis. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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19 pages, 1127 KiB  
Review
Flavonoids as a Natural Enhancer of Neuroplasticity—An Overview of the Mechanism of Neurorestorative Action
by Natalia Cichon, Joanna Saluk-Bijak, Leslaw Gorniak, Lukasz Przyslo and Michal Bijak
Antioxidants 2020, 9(11), 1035; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9111035 - 23 Oct 2020
Cited by 41 | Viewed by 4688
Abstract
Neuroplasticity is a complex physiological process occurring in the brain for its entire life. However, it is of particular importance in the case of central nervous system (CNS) disorders. Neurological recovery largely depends on the ability to reestablish the structural and functional organization [...] Read more.
Neuroplasticity is a complex physiological process occurring in the brain for its entire life. However, it is of particular importance in the case of central nervous system (CNS) disorders. Neurological recovery largely depends on the ability to reestablish the structural and functional organization of neurovascular networks, which must be pharmacologically supported. For this reason, new forms of therapy are constantly being sought. Including adjuvant therapies in standard treatment may support the enhancement of repair processes and restore impaired brain functions. The common hallmark of nerve tissue damage is increased by oxidative stress and inflammation. Thus, the studies on flavonoids with strong antioxidant and anti-inflammatory properties as a potential application in neuro intervention have been carried out for a long time. However, recent results have revealed another important property of these compounds in CNS therapy. Flavonoids possess neuroprotective activity, and promote synaptogenesis and neurogenesis, by, among other means, inhibiting oxidative stress and neuroinflammation. This paper presents an overview of the latest knowledge on the impact of flavonoids on the plasticity processes of the brain, taking into account the molecular basis of their activity. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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30 pages, 7904 KiB  
Review
An Update on the Role of Dietary Phytochemicals in Human Skin Cancer: New Insights into Molecular Mechanisms
by Salman Ul Islam, Muhammad Bilal Ahmed, Haseeb Ahsan, Mazharul Islam, Adeeb Shehzad, Jong Kyung Sonn and Young Sup Lee
Antioxidants 2020, 9(10), 916; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox9100916 - 25 Sep 2020
Cited by 14 | Viewed by 4260
Abstract
Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma [...] Read more.
Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma skin cancers. Phytochemicals present in the diet possess the desirable effects of protecting the skin from damaging free radicals as well as other benefits. Dietary phytochemicals appear to be effective in preventing skin cancer and are inexpensive, widely available, and well tolerated. Multiple in vitro and in vivo studies have demonstrated the significant anti-inflammatory, antioxidant, and anti-angiogenic characteristics of dietary phytochemicals against skin malignancy. Moreover, dietary phytochemicals affect multiple important cellular processes including cell cycle, angiogenesis, and metastasis to control skin cancer progression. Herein, we discuss the advantages of key dietary phytochemicals in whole fruits and vegetables, their bioavailability, and underlying molecular mechanisms for preventing skin cancer. Current challenges and future prospects for research are also reviewed. To date, most of the chemoprevention investigations have been conducted preclinically, and additional clinical trials are required to conform and validate the preclinical results in humans. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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Other

23 pages, 3061 KiB  
Systematic Review
Exploring the Impact of Flavonoids on Symptoms of Depression: A Systematic Review and Meta-Analysis
by Sawan Ali, Graziamaria Corbi, Michael Maes, Giovanni Scapagnini and Sergio Davinelli
Antioxidants 2021, 10(11), 1644; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111644 - 20 Oct 2021
Cited by 21 | Viewed by 779066
Abstract
Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary supplements. Our aim was to [...] Read more.
Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary supplements. Our aim was to conduct a systematic review to evaluate the effects of dietary flavonoids on the symptoms of depression. A total of 46 studies met the eligibility criteria. Of these, 36 were intervention trials and 10 were observational studies. A meta-analysis of 36 clinical trials involving a total of 2788 participants was performed. The results showed a statistically significant effect of flavonoids on depressive symptoms (mean difference = −1.65; 95% C.I., −2.54, −0.77; p < 0.01). Five of the 10 observational studies included in the systematic review reported significant results, suggesting that a higher flavonoid intake may improve symptoms of depression. Further studies are urgently required to elucidate whether causal and mechanistic links exist, along with substantiation of functional brain changes associated with flavonoid consumption. Full article
(This article belongs to the Special Issue The Pharma-Nutritional Role of Antioxidant Phytochemicals in Health and Disease)
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