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Catechins and Other Plant Polyphenols: From Nature to Medical Applications

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 26952

Special Issue Editors

Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
Interests: green tea; catechins; polyphenols; cancer; diabetes; obesity
Special Issues, Collections and Topics in MDPI journals
Institute for World Health Development, Mukogawa Women's University, Nishinomiya 663-8143, Hyogo, Japan
Interests: soybean; polyphenols; cardiovascular disease; epidemiology
School of Nutritional and Environmental Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan
Interests: green tea; catechins; polyphenols; fecal metabolites; lipid metabolism

Special Issue Information

Dear Colleagues,

Plants contain various polyphenols, which are believed to serve as self-defense agents. These include flavonoids, such as isoflavones, flavanols, and proanthocyanidins. Epidemiological studies have indicated that the consumption of diets containing polyphenols has a role in reducing the risk of various diseases, such as cancer, obesity, diabetes, and cardiovascular diseases (CVDs). Animal- and cell-based studies have provided evidence on what kinds of polyphenols are responsible for these health effects, as exemplified by tea catechins in cancer and soy flavonoids in CVD. However, conflicting results have also been reported, indicating that further investigations are required in order to gain solid information on the health benefits of the intake of polyphenols. After the success of two previous editions (Catechin in Health and Diseases (2018) and Catechins in Human Health 2020 (2020)), this Special Issue is intended to provide a forum for the latest information on the health-beneficial activities of polyphenols, including catechins. It will include review articles on epidemiological studies of polyphenols and original and review articles on dietary polyphenols related to action mechanisms, chemical modifications, comparative studies among polyphenols, and synergistic effects with a variety of drugs. In order to maintain the high quality of this Special Issue, the Editors request that the authors submit their manuscripts according to the following criteria: data which provide dose- and time-dependent effects in animal and cell-based experiments; for cell-based experiments, data from multiple cell lines should be presented. Cell-based and animal studies on plant extracts without having identified polyphenol compound(s) as being responsible for the bioactivity are not within the scope of this Issue.

Prof. Dr. Mamoru Isemura
Prof. Dr. Yukio Yamori
Dr. Noriyuki Miyoshi
Guest Editors

Manuscript Submission Information

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Keywords

  • health benefits of polyphenols
  • action mechanisms
  • chemical synthesis
  • comparative studies synergistic effects
  • epidemiology

Published Papers (10 papers)

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Research

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14 pages, 4136 KiB  
Article
Hyaluronic Acid–Zein Core-Shell Nanoparticles Improve the Anticancer Effect of Curcumin Alone or in Combination with Oxaliplatin against Colorectal Cancer via CD44-Mediated Cellular Uptake
by Lu Liu, Shufang Yang, Feng Chen and Ka-Wing Cheng
Molecules 2022, 27(5), 1498; https://doi.org/10.3390/molecules27051498 - 23 Feb 2022
Cited by 9 | Viewed by 2076
Abstract
Curcumin (CUR) has been reported to enhance the chemotherapeutic efficacy of oxaliplatin (OXA) in colorectal cancer (CRC) and inhibit OXA-induced side effects. However, shortcomings, including poor solubility and sensitivity to metabolic transformation, have greatly undermined its value in clinical applications. In this study, [...] Read more.
Curcumin (CUR) has been reported to enhance the chemotherapeutic efficacy of oxaliplatin (OXA) in colorectal cancer (CRC) and inhibit OXA-induced side effects. However, shortcomings, including poor solubility and sensitivity to metabolic transformation, have greatly undermined its value in clinical applications. In this study, the potential of CUR-encapsulated hyaluronic acid (HA)–zein composite nanoparticles (HZ-CUR) as an oral adjuvant for OXA-based chemotherapy was assessed in representative CRC models in mice. Cell viability and colony formation assays in three human CRC cell lines showed that HZ-CUR had a stronger anti-CRC effect than free CUR when given alone and a stronger synergistic effect when combined with OXA, especially in HCT116 and HT29 cell lines. Western blotting, cellular uptake, and RNA interference assays revealed that OXA-induced upregulation of CD44 likely contributed to enhanced cellular uptake of HZ-CUR and thus the enhanced anticancer effect. The significantly improved anti-CRC effects and potential underlying mechanism of HZ-CUR alone and in combination with OXA were further validated in a subcutaneous xenograft and an in situ CRC model in mice. These findings support that HZ-CUR may be an effective oral adjuvant for OXA-based CRC chemotherapy that would not only improve its efficacy but also help reduce the associated side effects. Full article
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11 pages, 662 KiB  
Article
Heartwood of Dalbergia cochinchinensis: 4,7,2′-Trihydroxy-4′-methoxyisoflavanol and 6,4′-Dihydroxy-7-methoxyflavane Reduce Cytokine and Chemokine Expression In Vitro
by Feng Shao, Layla Panahipour, Mariane Beatriz Sordi, Fangrui Tang, Ronghua Liu and Reinhard Gruber
Molecules 2022, 27(4), 1321; https://doi.org/10.3390/molecules27041321 - 15 Feb 2022
Cited by 1 | Viewed by 1586
Abstract
Dalbergia cochinchinensis has been widely used in traditional medicine because of its flavonoids; however, the impact of the flavonoids to modulate the inflammatory response to oral cells remains to be described. For this aim, we isolated 4,7,2′-trihydroxy-4′-methoxyisoflavanol (472T4MIF) and 6,4′-dihydroxy-7-methoxyflavane (64D7MF) from the [...] Read more.
Dalbergia cochinchinensis has been widely used in traditional medicine because of its flavonoids; however, the impact of the flavonoids to modulate the inflammatory response to oral cells remains to be described. For this aim, we isolated 4,7,2′-trihydroxy-4′-methoxyisoflavanol (472T4MIF) and 6,4′-dihydroxy-7-methoxyflavane (64D7MF) from the heartwood of D. cochinchinensis and confirmed the chemical structure by nuclear magnetic resonance. We show here that both flavonoids are inhibitors of an inflammatory response of murine RAW 264.7 inflammatory macrophages stimulated by LPS. This is indicated by interleukin (IL)1, IL6, and chemokine CCL2 production besides the phosphorylation of p65. Consistently, in primary murine macrophages, both flavonoids decreased the inflammatory response by lowering LPS-induced IL1 and IL6 expression. To introduce oral cells, we have used human gingival fibroblasts and provoked the inflammatory response by exposing them to IL1β and TNFα. Under these conditions, 472T4MIF, but not 64D7MF, reduced the expression of chemokines CXCL1 and CXCL2. Taken together, we identified two flavonoids that can reduce the expression of cytokines and chemokines in macrophages and fibroblastic cells. Full article
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14 pages, 3495 KiB  
Article
The Effects of Polyphenol, Tannic Acid, or Tannic Acid in Combination with Pamidronate on Human Osteoblast Cell Line Metabolism
by Hermizi Hapidin, Nor Munira Hashim, Mohamad Zahid Kasiram and Hasmah Abdullah
Molecules 2022, 27(2), 451; https://doi.org/10.3390/molecules27020451 - 11 Jan 2022
Cited by 3 | Viewed by 1824
Abstract
Background: This study investigates the effect of tannic acid (TA) combined with pamidronate (PAM) on a human osteoblast cell line. Methods: EC50 for TA, PAM, and different combination ratios of TA and PAM (25:75, 50:50, 75:25) were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) [...] Read more.
Background: This study investigates the effect of tannic acid (TA) combined with pamidronate (PAM) on a human osteoblast cell line. Methods: EC50 for TA, PAM, and different combination ratios of TA and PAM (25:75, 50:50, 75:25) were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The combination index value was utilized to analyze the degree of drug interaction, while trypan blue assay was applied to analyze the cells proliferation effect. The mineralization and detection of bone BSP and Osx genes were determined via histochemical staining and PCR test, respectively. Results: The EC50 of osteoblasts treated with TA and a 75:25 ratio of TA and PAM were more potent with lower EC50 at 0.56 µg/mL and 0.48 µg/mL, respectively. The combination of TA and PAM (75:25) was shown to have synergistic interaction. On Day 7, both TA and PAM groups showed significantly increased proliferation compared with control and combination groups. On Day 7, both the TA and combination-treated groups demonstrated a higher production of calcium deposits than the control and PAM-treated groups. Moreover, on Day 7, the combination-treated group showed a significantly higher expression of BSP and Osx genes than both the TA and PAM groups. Conclusion: Combination treatment of TA and PAM at 75:25 ameliorated the highest enhancement of osteoblast proliferation and mineralization as well as caused a high expression of BSP and Osx genes. Full article
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Review

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32 pages, 10601 KiB  
Review
Anti-Inflammatory Effects of Dietary Polyphenols through Inhibitory Activity against Metalloproteinases
by Takuji Suzuki, Tomokazu Ohishi, Hiroki Tanabe, Noriyuki Miyoshi and Yoriyuki Nakamura
Molecules 2023, 28(14), 5426; https://doi.org/10.3390/molecules28145426 - 15 Jul 2023
Cited by 2 | Viewed by 1802
Abstract
Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases that play important roles in a variety of diseases, including cancer, cardiovascular disease, diabetes, obesity, and brain diseases. Dietary polyphenols are thought to have a variety of beneficial effects on these diseases characterized by inflammation. Clinical studies [...] Read more.
Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases that play important roles in a variety of diseases, including cancer, cardiovascular disease, diabetes, obesity, and brain diseases. Dietary polyphenols are thought to have a variety of beneficial effects on these diseases characterized by inflammation. Clinical studies have demonstrated that MMPs are in most cases upregulated in various inflammatory diseases, including osteoarthritis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer’s disease. Studies using patient-derived human samples, animal studies, and cellular experiments have suggested that polyphenols may be beneficial against inflammatory diseases by suppressing MMP gene expression and enzyme activity. One important mechanism by which polyphenols exert their activity is the downregulation of reactive oxygen species that promote MMP expression. Another important mechanism is the direct binding of polyphenols to MMPs and their inhibition of enzyme activity. Molecular docking analyses have provided a structural basis for the interaction between polyphenols and MMPs and will help to explore new polyphenol-based drugs with anti-inflammatory properties. Full article
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22 pages, 3612 KiB  
Review
Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity
by Hiroki Tanabe, Takuji Suzuki, Tomokazu Ohishi, Mamoru Isemura, Yoriyuki Nakamura and Keiko Unno
Molecules 2023, 28(2), 525; https://doi.org/10.3390/molecules28020525 - 05 Jan 2023
Cited by 8 | Viewed by 1898
Abstract
Epidemiological studies have shown that the consumption of green tea has beneficial effects against cancer. Basic studies have provided evidence that epigallocatechin gallate (EGCG) is a major contributor to these effects. Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases with the ability to degrade the [...] Read more.
Epidemiological studies have shown that the consumption of green tea has beneficial effects against cancer. Basic studies have provided evidence that epigallocatechin gallate (EGCG) is a major contributor to these effects. Matrix metalloproteinases (MMPs) are zinc-dependent metalloproteinases with the ability to degrade the extracellular matrix proteins and are involved in various diseases including cancer in which MMPs have a critical role in invasion and metastasis. In this review, we discuss the effects of EGCG on several types of MMPs in the context of its anticancer activity. In the promoter region, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species. EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and β-catenin levels, leading to suppression of MMPs’ expression. Other mechanisms by which EGCG inhibits MMPs include direct binding to MMPs to prevent their activation and downregulation of NF-κB to suppress the production of inflammatory cytokines such as TNFα and IL-1β. Findings from studies on EGCG presented here may be useful in the development of more effective anti-MMP agents, which would give beneficial effects on cancer and other diseases. Full article
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20 pages, 8135 KiB  
Review
Health Effects of Soy Isoflavones and Green Tea Catechins on Cancer and Cardiovascular Diseases Based on Urinary Biomarker Levels
by Tomokazu Ohishi, Noriyuki Miyoshi, Mari Mori, Miki Sagara and Yukio Yamori
Molecules 2022, 27(24), 8899; https://doi.org/10.3390/molecules27248899 - 14 Dec 2022
Cited by 1 | Viewed by 2058
Abstract
Plant polyphenols have various health effects. Genistein, which is abundant in soybeans, and epigallocatechin-3-gallate, which is abundant in green tea, are major flavonoids, a subclass group of polyphenols. Several epidemiological studies have shown that these flavonoids have beneficial effects against cancer and cardiovascular [...] Read more.
Plant polyphenols have various health effects. Genistein, which is abundant in soybeans, and epigallocatechin-3-gallate, which is abundant in green tea, are major flavonoids, a subclass group of polyphenols. Several epidemiological studies have shown that these flavonoids have beneficial effects against cancer and cardiovascular diseases. However, other studies did not show such effects. Several confounding factors, including recall bias, are related to these inconsistent findings, and the determination of metabolites in the urine may be useful in reducing the number of confounding factors. Equipment, which can be used by research participants to collect samples from a portion of voided urine within 24 h without the help of medical workers, has been developed for epidemiological investigations. Previous studies, in which flavonoid metabolites in these urine samples were measured, revealed that soy intake was correlated with a reduced risk of certain types of cancer and cardiovascular diseases worldwide. Although soybeans and green tea consumption may have protective effects against cancer and cardiovascular diseases, further clinical studies that consider different confounding factors are required to provide evidence for the actual impact of dietary flavonoids on human diseases, including cancer and cardiovascular diseases. One possible mechanism involved is discussed in relation to the downregulation of reactive oxygen species and the upregulation of 5′-adenosine monophosphate-activated protein kinase elicited by these flavonoids. Full article
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25 pages, 4684 KiB  
Review
Influence of Age and Dose on the Effect of Resveratrol for Glycemic Control in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis
by Beatriz Isabel García-Martínez, Mirna Ruiz-Ramos, José Pedraza-Chaverri, Edelmiro Santiago-Osorio and Víctor Manuel Mendoza-Núñez
Molecules 2022, 27(16), 5232; https://doi.org/10.3390/molecules27165232 - 16 Aug 2022
Cited by 13 | Viewed by 3535
Abstract
Background: Several clinical trials have suggested that resveratrol has hypoglycemic properties; however, there are other studies in which such an effect has not been observed. Methods: We carried out a systematic search in several databases; seventeen studies were selected for the systematic review [...] Read more.
Background: Several clinical trials have suggested that resveratrol has hypoglycemic properties; however, there are other studies in which such an effect has not been observed. Methods: We carried out a systematic search in several databases; seventeen studies were selected for the systematic review and fifteen were included in the meta-analysis. Results: Resveratrol decreases glucose levels in subjects aged 45–59 years at doses <250 mg/day (−8.64 mg/dL, p < 0.00001), 250–500 mg/day (−22.24 mg/dL, p = 0.0003), and 500–1000 mg/day (−28.40 mg/dL, p = 0.0008), while in subjects older than 60 years, it only decreases with doses of 250–500 mg/day. Likewise, HbA1c improved in subjects aged 45–59 years with doses of 250–500 mg (−0.60%, p < 0.00001), but not in subjects older than 60 years. Insulin levels improved in subjects aged 45–59 years with doses < 250 mg/day (−0.80 mIU/L, p = 0.0003) and doses of 250–500 mg/day (−5.0 mIU/L, p = 0.0003), although in subjects older than 60 years, they only improved with doses of 250–500 mg/day (−1.79 mIU/L, p = 0.01). On the other hand, HOMA-IR only improved in subjects older than 60 years with doses of 250–500 mg/day (−0.40, p = 0.01). Conclusions: Resveratrol has a statistically significant dose–response effect on glucose concentrations, HbA1c, and insulin levels; however, there is not enough scientific evidence to propose a therapeutic dose. Full article
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25 pages, 3873 KiB  
Review
67-kDa Laminin Receptor-Mediated Cellular Sensing System of Green Tea Polyphenol EGCG and Functional Food Pairing
by Yoshinori Fujimura, Motofumi Kumazoe and Hirofumi Tachibana
Molecules 2022, 27(16), 5130; https://doi.org/10.3390/molecules27165130 - 11 Aug 2022
Cited by 14 | Viewed by 2595
Abstract
The body is equipped with a “food factor-sensing system” that senses food factors, such as polyphenols, sulfur-containing compounds, and vitamins, taken into the body, and plays an essential role in manifesting their physiological effects. For example, (−)-epigallocatechin-3-O-gallate (EGCG), the representative catechin [...] Read more.
The body is equipped with a “food factor-sensing system” that senses food factors, such as polyphenols, sulfur-containing compounds, and vitamins, taken into the body, and plays an essential role in manifesting their physiological effects. For example, (−)-epigallocatechin-3-O-gallate (EGCG), the representative catechin in green tea (Camellia sinensi L.), exerts various effects, including anti-cancer, anti-inflammatory, and anti-allergic effects, when sensed by the cell surficial protein 67-kDa laminin receptor (67LR). Here, we focus on three representative effects of EGCG and provide their specific signaling mechanisms, the 67LR-mediated EGCG-sensing systems. Various components present in foods, such as eriodictyol, hesperetin, sulfide, vitamin A, and fatty acids, have been found to act on the food factor-sensing system and affect the functionality of other foods/food factors, such as green tea extract, EGCG, or its O-methylated derivative at different experimental levels, i.e., in vitro, animal models, and/or clinical trials. These phenomena are observed by increasing or decreasing the activity or expression of EGCG-sensing-related molecules. Such functional interaction between food factors is called “functional food pairing”. In this review, we introduce examples of functional food pairings using EGCG. Full article
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22 pages, 1161 KiB  
Review
Anti-Cancer Effects of Dietary Polyphenols via ROS-Mediated Pathway with Their Modulation of MicroRNAs
by Yasukiyo Yoshioka, Tomokazu Ohishi, Yoriyuki Nakamura, Ryuuta Fukutomi and Noriyuki Miyoshi
Molecules 2022, 27(12), 3816; https://doi.org/10.3390/molecules27123816 - 14 Jun 2022
Cited by 23 | Viewed by 2574
Abstract
Consumption of coffee, tea, wine, curry, and soybeans has been linked to a lower risk of cancer in epidemiological studies. Several cell-based and animal studies have shown that dietary polyphenols like chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin and resveratrol play a [...] Read more.
Consumption of coffee, tea, wine, curry, and soybeans has been linked to a lower risk of cancer in epidemiological studies. Several cell-based and animal studies have shown that dietary polyphenols like chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin and resveratrol play a major role in these anticancer effects. Several mechanisms have been proposed to explain the anticancer effects of polyphenols. Depending on the cellular microenvironment, these polyphenols can exert double-faced actions as either an antioxidant or a prooxidant, and one of the representative anticancer mechanisms is a reactive oxygen species (ROS)-mediated mechanism. These polyphenols can also influence microRNA (miR) expression. In general, they can modulate the expression/activity of the constituent molecules in ROS-mediated anticancer pathways by increasing the expression of tumor-suppressive miRs and decreasing the expression of oncogenic miRs. Thus, miR modulation may enhance the anticancer effects of polyphenols through the ROS-mediated pathways in an additive or synergistic manner. More precise human clinical studies on the effects of dietary polyphenols on miR expression will provide convincing evidence of the preventive roles of dietary polyphenols in cancer and other diseases. Full article
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20 pages, 2202 KiB  
Review
Potential Effects of Soy Isoflavones on the Prevention of Metabolic Syndrome
by Kazuo Yamagata and Yukio Yamori
Molecules 2021, 26(19), 5863; https://doi.org/10.3390/molecules26195863 - 27 Sep 2021
Cited by 29 | Viewed by 5168
Abstract
Isoflavones are polyphenols primarily contained in soybean. As phytoestrogens, isoflavones exert beneficial effects on various chronic diseases. Metabolic syndrome increases the risk of death due to arteriosclerosis in individuals with various pathological conditions, including obesity, hypertension, hyperglycemia, and dyslipidemia. Although the health benefits [...] Read more.
Isoflavones are polyphenols primarily contained in soybean. As phytoestrogens, isoflavones exert beneficial effects on various chronic diseases. Metabolic syndrome increases the risk of death due to arteriosclerosis in individuals with various pathological conditions, including obesity, hypertension, hyperglycemia, and dyslipidemia. Although the health benefits of soybean-derived isoflavones are widely known, their beneficial effects on the pathogenesis of metabolic syndrome are incompletely understood. This review aims to describe the association between soybean-derived isoflavone intake and the risk of metabolic syndrome development. We reviewed studies on soy isoflavones, particularly daidzein and genistein, and metabolic syndrome, using PubMed, ScienceDirect, and Web of Science. We describe the pathological characteristics of metabolic syndrome, including those contributing to multiple pathological conditions. Furthermore, we summarize the effects of soybean-derived daidzein and genistein on metabolic syndrome reported in human epidemiological studies and experiments using in vitro and in vivo models. In particular, we emphasize the role of soy isoflavones in metabolic syndrome-induced cardiovascular diseases. In conclusion, this review focuses on the potential of soy isoflavones to prevent metabolic syndrome by influencing the onset of hypertension, hyperglycemia, dyslipidemia, and arteriosclerosis and discusses the anti-inflammatory effects of isoflavones. Full article
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