Special Issue "The Effects of Phytochemicals on Health Benefit"

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

Deadline for manuscript submissions: closed (1 June 2020).

Special Issue Editors

Prof. Dr. Mariko Uehara
Website
Guest Editor
Department of Nutritional Science and Food Safety, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
Interests: polyphenols; phytoestrogens; flavonoids; isoflavonoids; sulfur compounds; prebiotics; osteoporosis; diabetes; redox homeostasis; minerals
Prof. Dr. Yoshiko Ishimi
Website1 Website2
Guest Editor
Tokyo University of Agriculture, NODAI Research Institute, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan
Interests: nutrition; phytoestrogen; bone metabolism; women’s health; food science; nutrition labeling

Special Issue Information

Dear Colleagues,

Phytochemicals in vegetables and fruits are considered to be responsible for health benefits. Dietary phytochemicals are inversely associated with the risk of several chronic diseases, such as cancer, cardiovascular diseases, diabetes mellitus, and osteoporosis. Recently, it has also been reported that some phytochemicals may enhance brain function and antiaging. Phytochemical metabolism is interesting as well. It is known that recent clinical effectiveness of phytochemicals on health benefits might be due to their metabolites by the intestinal microbiota. This Special Issue focuses on the antioxidant defenses, anti-inflammatory efficacies, and estrogenic activities of phytochemicals including their metabolites, and how phytochemicals contribute to health benefits and antiaging, especially in lowering the risk of metabolic syndrome, locomotive syndrome, brain function, and so on. Furthermore, we should discuss and elucidate their mechanisms, because those are not all the same. 

Prof. Dr. Mariko Uehara
Prof. Dr. Yoshiko Ishimi
Guest Editors

Manuscript Submission Information

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Keywords

  • Polyphenols
  • Phytoestrogens
  • Carotenoids
  • Phytochemical metabolites
  • Antioxidants
  • Anti-inflammatory substances
  • Metabolic syndrome
  • Locomotive syndrome
  • Chronic diseases
  • Brain function

Published Papers (8 papers)

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Research

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Open AccessArticle
Acute and Chronic Effects of Green Oat (Avena sativa) Extract on Cognitive Function and Mood during a Laboratory Stressor in Healthy Adults: A Randomised, Double-Blind, Placebo-Controlled Study in Healthy Humans
Nutrients 2020, 12(6), 1598; https://doi.org/10.3390/nu12061598 (registering DOI) - 29 May 2020
Abstract
Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may [...] Read more.
Green oat (Avena sativa) extracts contain several groups of potentially psychoactive phytochemicals. Previous research has demonstrated improvements in cognitive function following a single dose of these extracts, but not following chronic supplementation. Additionally, whilst green oat extracts contain phytochemicals that may improve mood or protect against stress, for instance species-specific triterpene saponins, to date this possibility has not been examined. The current study investigated the effects of a single dose and four weeks of administration of a novel, Avena sativa herbal extract (cognitaven®) on cognitive function and mood, and changes in psychological state during a laboratory stressor. The study adopted a dose-ranging, double-blind, randomised, parallel groups design in which 132 healthy males and females (35 to 65 years) received either 430 mg, 860 mg, 1290 mg green oat extract or placebo for 29 days. Assessments of cognitive function, mood and changes in psychological state during a laboratory stressor (Observed Multitasking Stressor) were undertaken pre-dose and at 2 h and 4 h post-dose on the first (Day 1) and last days (Day 29) of supplementation. The results showed that both a single dose of 1290 mg and, to a greater extent, supplementation for four weeks with both 430 mg and 1290 mg green oat extract resulted in significantly improved performance on a computerised version of the Corsi Blocks working memory task and a multitasking task (verbal serial subtractions and computerised tracking) in comparison to placebo. After four weeks, the highest dose also decreased the physiological response to the stressor in terms of electrodermal activity. There were no treatment-related effects on mood. These results confirm the acute cognitive effects of Avena sativa extracts and are the first to demonstrate that chronic supplementation can benefit cognitive function and modulate the physiological response to a stressor. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
Open AccessArticle
Punicalagin Protects Diabetic Nephropathy by Inhibiting Pyroptosis Based on TXNIP/NLRP3 Pathway
Nutrients 2020, 12(5), 1516; https://doi.org/10.3390/nu12051516 - 22 May 2020
Abstract
Diabetic nephropathy is a diabetic complication caused by chronic inflammation. As the primary polyphenol in pomegranate, punicalagin is believed to have significant anti-inflammatory properties. In this study, we established a mice model for diabetes induced by high-fat diet (HFD)/ streptozotocin (STZ) to verify [...] Read more.
Diabetic nephropathy is a diabetic complication caused by chronic inflammation. As the primary polyphenol in pomegranate, punicalagin is believed to have significant anti-inflammatory properties. In this study, we established a mice model for diabetes induced by high-fat diet (HFD)/ streptozotocin (STZ) to verify the protective effect of punicalagin in vivo. The results show that the blood urea nitrogen (BUN), serum creatinine (CREA), and the urine albumin to creatinine ratio (UACR) were significantly decreased in diabetic mice after punicalagin intervention, and the symptoms of glomerular interstitial hyperplasia and glomerular hypertrophy were alleviated. Pyroptosis is an essential manner of programmed cell death in the inflammatory response; the expression of pyroptosis-related proteins such as interleukin-1 (IL-1β), cysteinyl aspartate-specific protease-1 (caspase-1), gasdermin D (GSDMD), and nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) was decreased in our study, which proved that the administration of punicalagin for eight weeks can significantly inhibit pyroptosis in mice. In addition, punicalagin reduced high glucose-mediated protein expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and alleviated mitochondria damage. Low expression of NOX4 inhibits the dissociation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP) and the suppression of NLRP3 inflammasome activation. To summarize, our study provided evidence that punicalagin can alleviate diabetic nephropathy, and the effect is associated with downregulating the expression of NOX4, inhibiting TXNIP/NLRP3 pathway-mediated pyroptosis, suggesting its therapeutic implications for complications of diabetes. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
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Open AccessArticle
Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes
Nutrients 2020, 12(5), 1479; https://doi.org/10.3390/nu12051479 - 20 May 2020
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, sometimes ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Various hits including excessive hepatic steatosis, oxidative stress, apoptosis, and inflammation, contribute to NASH development. Gallic acid (GA), [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, sometimes ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Various hits including excessive hepatic steatosis, oxidative stress, apoptosis, and inflammation, contribute to NASH development. Gallic acid (GA), a natural polyphenol, was reported to exert a protective effect on hepatic steatosis in animal models, but the precise molecular mechanisms remain unclear. Here, we examined the effect of GA on hepatic lipid accumulation, apoptosis, and inflammatory response caused by hepatocyte–macrophage crosstalk. We demonstrated that GA attenuated palmitic acid (PA)-induced fat accumulation via the activation of AMP-activated protein kinase (AMPK) in HepG2 cells. GA also ameliorated cell viability and suppressed apoptosis-related gene expression and caspase 3/7 activity induced by PA and H2O2. In a co-culture of lipid-laden Hepa 1-6 hepatocytes and RAW 264 macrophages, GA reduced inflammatory mediator expression and induced antioxidant enzyme expression. These results indicate that GA suppresses hepatic lipid accumulation, apoptosis, and inflammation caused by the interaction between hepatocytes and macrophages. The potential effects of GA observed in our study could be effective in preventing NASH and its complications. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
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Open AccessArticle
Biological and Computational Studies for Dual Cholinesterases Inhibitory Effect of Zerumbone
Nutrients 2020, 12(5), 1215; https://doi.org/10.3390/nu12051215 - 25 Apr 2020
Abstract
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer’s disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase [...] Read more.
Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) mediate the degradation of acetylcholine (ACh), a primary neurotransmitter in the brain. Cholinergic deficiency occurs during the progression of Alzheimer’s disease (AD), resulting in widespread cognitive dysfunction and decline. We evaluated the potential effect of a natural cholinesterase inhibitor, zerumbone, using in vitro target enzyme assays, as well as in silico docking and ADMET (absorption, distribution, metabolism, excretion, and toxicity) simulation. Zerumbone showed a predominant cholinesterase inhibitory property with IC50 values of 2.74 ± 0.48 µM and 4.12 ± 0.42 µM for AChE and BChE, respectively; however, the modes of inhibition were different. Computational docking simulation indicated that Van der Waals interactions between zerumbone and both the cholinesterases were the main forces responsible for its inhibitory effects. Furthermore, zerumbone showed the best physicochemical properties for both bioavailability and blood–brain barrier (BBB) permeability. Together, in the present study, zerumbone was clearly identified as a unique dual AChE and BChE inhibitor with high permeability across the BBB, suggesting a strong potential for its physiological benefits and/or pharmacological efficacy in the prevention of AD. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
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Open AccessArticle
Indole-3-Carbinol Inhibits Citrobacter rodentium Infection through Multiple Pathways Including Reduction of Bacterial Adhesion and Enhancement of Cytotoxic T Cell Activity
Nutrients 2020, 12(4), 917; https://doi.org/10.3390/nu12040917 - 27 Mar 2020
Abstract
Intestinal inflammation is associated with an increased risk of developing colorectal cancer and may result from dysregulated responses to commensal bacteria or exposure to bacterial pathogens. Dietary modulation of intestinal inflammation may protect against development of colon cancer. However, the precise diet-derived components [...] Read more.
Intestinal inflammation is associated with an increased risk of developing colorectal cancer and may result from dysregulated responses to commensal bacteria or exposure to bacterial pathogens. Dietary modulation of intestinal inflammation may protect against development of colon cancer. However, the precise diet-derived components and underlying mechanisms remain elusive. Citrobacter rodentium (Cr) induces acute intestinal inflammation and has been used to study the role of inflammation in the susceptibility to colon cancer. Here we examine the effects of indole-3-carbinol (I3C), a dietary compound with anticarcinogenic properties, on intestinal immune and inflammatory responses to Cr infection and adhesion to colonic cells in vitro. C57BL/6J mice were fed a diet with/without 1 μmol/g I3C and infected with Cr. Compared to infected mice fed with a control diet, consumption of a 1 μmol I3C/g diet significantly reduced fecal excretion of Cr, Cr colonization of the colon, and reduced colon crypt hyperplasia. Furthermore, expression of Cr-induced inflammatory markers such as IL-17A, IL-6, and IL1β were attenuated in infected mice fed with the I3C diet, compared to mice fed a control diet. The expression of cytotoxic T cell markers CD8 and FasL mRNA were increased in I3C-fed infected mice. In-vitro, I3C inhibited Cr growth and adhesion to Caco-2 cells. I3C alleviates Cr-induced murine colitis through multiple mechanisms including inhibition of Cr growth and adhesion to colonic cells in vitro and enhancement of cytotoxic T cell activity. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
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Open AccessArticle
Modulation of Adhesion Process, E-Selectin and VEGF Production by Anthocyanins and Their Metabolites in an In Vitro Model of Atherosclerosis
Nutrients 2020, 12(3), 655; https://doi.org/10.3390/nu12030655 - 28 Feb 2020
Abstract
The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo-3-glc and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of vascular cell adhesion [...] Read more.
The present study aims to evaluate the ability of peonidin and petunidin-3-glucoside (Peo-3-glc and Pet-3-glc) and their metabolites (vanillic acid; VA and methyl-gallic acid; MetGA), to prevent monocyte (THP-1) adhesion to endothelial cells (HUVECs), and to reduce the production of vascular cell adhesion molecule (VCAM)-1, E-selectin and vascular endothelial growth factor (VEGF) in a stimulated pro-inflammatory environment, a pivotal step of atherogenesis. Tumor necrosis factor-α (TNF-α; 100 ng mL−1) was used to stimulate the adhesion of labelled monocytes (THP-1) to endothelial cells (HUVECs). Successively, different concentrations of Peo-3-glc and Pet-3-glc (0.02 µM, 0.2 µM, 2 µM and 20 µM), VA and MetGA (0.05 µM, 0.5 µM, 5 µM and 50 µM) were tested. After 24 h, VCAM-1, E-selectin and VEGF were quantified by ELISA, while the adhesion process was measured spectrophotometrically. Peo-3-glc and Pet-3-glc (from 0.02 µM to 20 µM) significantly (p < 0.0001) decreased THP-1 adhesion to HUVECs at all concentrations (−37%, −24%, −30% and −47% for Peo-3-glc; −37%, −33%, −33% and −45% for Pet-3-glc). VA, but not MetGA, reduced the adhesion process at 50 µM (−21%; p < 0.001). At the same concentrations, a significant (p < 0.0001) reduction of E-selectin, but not VCAM-1, was documented. In addition, anthocyanins and their metabolites significantly decreased (p < 0.001) VEGF production. The present findings suggest that while Peo-3-glc and Pet-3-glc (but not their metabolites) reduced monocyte adhesion to endothelial cells through suppression of E-selectin production, VEGF production was reduced by both anthocyanins and their metabolites, suggesting a role in the regulation of angiogenesis. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
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Open AccessArticle
Withania somnifera Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle
Nutrients 2020, 12(2), 431; https://doi.org/10.3390/nu12020431 - 07 Feb 2020
Abstract
Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. [...] Read more.
Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
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Review

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Open AccessReview
The Influence of Polyphenol Compounds on Human Gastrointestinal Tract Microbiota
Nutrients 2020, 12(2), 350; https://doi.org/10.3390/nu12020350 - 29 Jan 2020
Abstract
Polyphenols form a diverse group of compounds containing at least two hydroxyl groups in their chemical structure. Because of the common presence in plant kingdom, polyphenols are considered a significant component of food and an important group of compounds with antioxidant properties. The [...] Read more.
Polyphenols form a diverse group of compounds containing at least two hydroxyl groups in their chemical structure. Because of the common presence in plant kingdom, polyphenols are considered a significant component of food and an important group of compounds with antioxidant properties. The absorption of polyphenols present in food depends mostly on the activity of intestinal microflora. However, little is known about the processes and interactions responsible for such phenomenon in guts ecosystem. There are only few available publications that examine the effect on polyphenols on intestinal microbiota. Therefore, this work will focus on describing the relationship between polyphenol compounds present in food and bacteria colonizing the intestines, their mechanism, and impact on human’s health. Full article
(This article belongs to the Special Issue The Effects of Phytochemicals on Health Benefit)
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