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Polyphenols and Human Being: From Epidemiology to Molecular Targets

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

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 58069

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Dr. Celestino Santos-Buelga

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Department of “Nutrición y Bromatología” (Food Science and Nutrition), Facultad de Farmacia, Universidad de Salamanca (Spain), Campus Miguel de Unamuno, E37007 Salamanca, Spain
Interests: food; phenolic compounds; anthocyanins; flavonoids; metabolites; biological activity; health implication
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Special Issue Information

Dear colleagues,

Polyphenols are one of the largest groups of plant secondary metabolites. They play relevant roles in plant ecology and plant physiology and are also widely distributed in the human diet, contributing to sensory, technological, and health properties of plant-derived foods. Several thousand polyphenols have been identified in plants, foods, and human tissues and fluids, with a chemical nature, structural complexity, and concentrations that notably differ among matrices, making their study challenging. Furthermore, a large amount of epidemiological evidence has been accummulated relating polyphenol intake with prevention against chronic and age-related diseases, such as cardiovascular diseases, cognitive decline, and different types of cancers. Although polyphenols have been shown to possess a variety of in vitro and ex vivo biological activities, such as antioxidant, anti-inflammatory, estrogenic, antimicrobial or antitumor abilities, direct evidence in humans is still scarce, and further knowledge is required regarding aspects such as bioavailability, metabolism, interactions with gut microbiota or biological and molecular targets. All these issues are intended to be dealt with in the present Special Issue, where a large scope of subjects can fit in, from chemical characterization of phenolic metabolites to epidemiological issues, dietary intake, biomarkers, or metabolic targets.

We cordially invite you to participate in this Special Issue by submitting a contribution from your field of expertise in the study of polyphenols as related to human health, either an original research paper, a short communication or a specialized comprehensive review. In this latter case, the precise subject must be previously agreed with this guest editor, so as to prevent possible overlapping.

Prof. Celestino Santos-Buelga
Guest Editor

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Keywords

Dietary intake
Epidemiology
Biomarkers
Metabolites
Antioxidant
Antitumor
Anti-inflammatory
Antimicrobial
Efficacy/toxicity
Interactions with gut microbiota
Studies in model systems
Human studies
Drug design

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Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 208 KiB

Open AccessEditorial

Polyphenols and Human Beings: From Epidemiology to Molecular Targets

by Celestino Santos-Buelga

Molecules 2021, 26(14), 4218; https://doi.org/10.3390/molecules26144218 - 12 Jul 2021

Cited by 5 | Viewed by 2641

Abstract

Dietary polyphenols have been associated with health benefits in the prevention of a range of degenerative and age-related diseases that constitute the major causes of death and incapacitation in developed countries [...] Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

Research

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14 pages, 2342 KiB

Open AccessArticle

A Red-Berry Mixture as a Nutraceutical: Detailed Composition and Neuronal Protective Effect

by Noelia Carballeda-Sangiao, Susana Chamorro and Sonia de Pascual-Teresa

Molecules 2021, 26(11), 3210; https://doi.org/10.3390/molecules26113210 - 27 May 2021

Cited by 7 | Viewed by 2728

Abstract

Recommendations towards increased consumption of fresh fruit and vegetables are well supported by epidemiological and clinical trials. However, in some specific cases, it is difficult to follow these recommendations and the use of nutraceuticals or, in the present work, a freeze-dried fruits mixture can be recommended in order to afford the optimal consumption of dietary polyphenols naturally present in fruits and vegetables. In this work we have carefully characterized a red-berry mixture in terms of polyphenol composition, encountering mainly anthocyanins, which account for a total of 2.8 mg/g as cyanidin-3-glucoside equivalents. Additionally, we have assayed the red-berry blend in a cell model of neurological damage by differentiating the cells and measuring the effect of red-berry polyphenols on cell viability and redox state by flow cytometry. The berry-fruit extract showed an inhibitory effect on differentiated SH-SY5Y ROS formation at a concentration as low as 250 µg/mL (33% inhibition). The results show the potential of this berry-fruit blend for its nutraceutical use in the prevention of the neurodegeneration associated with age or environmental agents. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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16 pages, 1731 KiB

Open AccessArticle

Caffeic and Dihydrocaffeic Acids Promote Longevity and Increase Stress Resistance in Caenorhabditis elegans by Modulating Expression of Stress-Related Genes

by Sofia M. Gutierrez-Zetina, Susana González-Manzano, Begoña Ayuda-Durán, Celestino Santos-Buelga and Ana M. González-Paramás

Molecules 2021, 26(6), 1517; https://doi.org/10.3390/molecules26061517 - 10 Mar 2021

Cited by 19 | Viewed by 2964

Abstract

Caffeic and dihydrocaffeic acid are relevant microbial catabolites, being described as products from the degradation of different phenolic compounds i.e., hydroxycinnamoyl derivatives, anthocyanins or flavonols. Furthermore, caffeic acid is found both in free and esterified forms in many fruits and in high concentrations in coffee. These phenolic acids may be responsible for a part of the bioactivity associated with the intake of phenolic compounds. With the aim of progressing in the knowledge of the health effects and mechanisms of action of dietary phenolics, the model nematode Caenorhabditis elegans has been used to evaluate the influence of caffeic and dihydrocaffeic acids on lifespan and the oxidative stress resistance. The involvement of different genes and transcription factors related to longevity and stress resistance in the response to these phenolic acids has also been explored. Caffeic acid (CA, 200 μM) and dihydrocaffeic acid (DHCA, 300 μM) induced an increase in the survival rate of C. elegans under thermal stress. Both compounds also increased the mean and maximum lifespan of the nematode, compared to untreated worms. In general, treatment with these acids led to a reduction in intracellular ROS concentrations, although not always significant. Results of gene expression studies conducted by RT-qPCR showed that the favorable effects of CA and DHCA on oxidative stress and longevity involve the activation of several genes related to insulin/IGF-1 pathway, such as daf-16, daf-18, hsf-1 and sod-3, as well as a sirtuin gene (sir-2.1). Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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Graphical abstract

16 pages, 14176 KiB

Open AccessArticle

A Polyphenols-Rich Extract from Moricandia sinaica Boiss. Exhibits Analgesic, Anti-Inflammatory and Antipyretic Activities In Vivo

by Sahar El-mekkawy, Abdelaaty A. Shahat, Ali S. Alqahtani, Mansour S. Alsaid, Mohamed A.O. Abdelfattah, Riaz Ullah, Mahmoud Emam, Abdelaziz Yasri and Mansour Sobeh

Molecules 2020, 25(21), 5049; https://doi.org/10.3390/molecules25215049 - 30 Oct 2020

Cited by 20 | Viewed by 2786

Abstract

In this study, the aerial parts of Moricandia sinaica were evaluated for their in vivo analgesic, anti-inflammatory and antipyretic activities. The analgesic activities were examined using acetic acid-induced writhing, the hot plate test and the tail flick method. The anti-inflammatory and the antipyretic activities were evaluated using carrageenan-induced paw edema in rats and brewer’s yeast-induced pyrexia in mice, respectively. The aqueous fraction of the methanol extract (MS-3) showed to be the most bioactive among the other investigated fractions. At the dose of 500 mg/kg, the fraction (MS-3) showed a significant percentage inhibition of the carrageenan-induced edema by 52.4% (p < 0.05). In addition, MS-3 exhibited a significant inhibition of acetic acid-induced writhes by 44.4% and 61.5% (p < 0.001) at 250-mg/kg and 500-mg/kg doses, respectively. At 120 min post-treatment, the rat groups treated with MS-3 displayed statistically significant reduction in rectal temperature (p < 0.001) by 1.7 °C and 2.2 °C at 250- and 500-mg/kg doses, respectively. The phytochemical composition of the fraction (MS-3) was characterized by high-performance liquid chromatography-mass spectrometry (HPLC-PDA-MS/MS). Molecular docking studies demonstrated that the polyphenols identified in MS-3 revealed good binding energy upon docking to some target proteins involved in pain response and inflammation, such as the cannabinoid receptors CB1 and CB2, the fatty acid amide hydrolase (FAAH) and the cyclooxygenase COX-1 and COX-2 enzymes. Based on the findings from the present work, it could be concluded that the aerial parts extract of M. sinaica exerts potential analgesic, anti-inflammatory and antipyretic effects in rats. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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17 pages, 2839 KiB

Open AccessArticle

The Influence of Hemp Extract in Combination with Ginger on the Metabolic Activity of Metastatic Cells and Microorganisms

by Taja Žitek, Maja Leitgeb, Andrej Golle, Barbara Dariš, Željko Knez and Maša Knez Hrnčič

Molecules 2020, 25(21), 4992; https://doi.org/10.3390/molecules25214992 - 28 Oct 2020

Cited by 20 | Viewed by 4213

Abstract

This study presents an investigation of the anticancer and antimicrobial ability of a combination of ginger and cannabis extracts in different ratios (1:1, 7:3 and 3:7). Extracts were obtained using various methods (Soxhlet extractions, cold macerations, ultrasonic extractions and supercritical fluid extractions). The antioxidant activity and the presence of total phenols were measured in the extracts, and the effect of the application extracts in various concentrations (c = 50, 20, 10, 5, 1, 0.1, 0.01 mg/mL) on cells was investigated. Higher values of antioxidants were measured at the ratio where ginger was predominant, which is reflected in a higher concentration of total phenols. Depending on the polyphenol content, the extracts were most effective when prepared supercritically and ultrasonically. However, with respect to cell response, the ratio was shown to have no effect on inhibiting cancer cell division. The minimum concentration required to inhibit cancer cell growth was found to be 1 mg/mL. High-performance liquid chromatography (HPLC) analysis also confirmed the effectiveness of ultrasonic and supercritical fluid extraction, as their extracts reached higher cannabinoid contents. In both extractions, the cannabidiol (CBD) content was above 30% and the cannabidiolic acid (CBDA) content was above 45%. In the case of ultrasonic extraction, a higher quantity of cannabigerol (CBG) (5.75 ± 0.18) was detected, and in the case of supercritical fluid extraction, higher cannabichromene (CBC) (5.48 ± 0.13) content was detected, when compared to other extraction methods. The antimicrobial potential of extracts prepared with ultrasonic and supercritical extractions on three microorganisms (Staphylococcus aureus, Escherichia coli and Candida albicans) was checked. Ginger and cannabis extract show better growth inhibition of microorganisms in cannabis-dominated ratios for gram-positive bacterium S. aureus, MIC = 9.38 mg/mL, for gram-negative bacterium E. coli, MIC > 37.5 mg/mL and for the C. albicans fungus MIC = 4.69 mg/mL. This suggests guidelines for further work: a 1: 1 ratio of ginger and hemp will be chosen in a combination with supercritical and ultrasonic extraction. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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10 pages, 3392 KiB

Open AccessCommunication

Protective Effect of Flavonoids from Ohwia caudata against Influenza a Virus Infection

by Eun Bin Kwon, Hye Jin Yang, Jang-Gi Choi and Wei Li

Molecules 2020, 25(19), 4387; https://doi.org/10.3390/molecules25194387 - 24 Sep 2020

Cited by 14 | Viewed by 2882

Abstract

To identify new potential anti-influenza compounds, we isolated six flavonoids, 2′-hydroxyl yokovanol (1), 2′-hydroxyl neophellamuretin (2), yokovanol (3), swertisin (4), spinosin (5), and 7-methyl-apigenin-6-C-β-glucopyranosyl 2″-O-β-d-xylopyranoside (6) from MeOH extractions of Ohwia caudata. We screened these compounds for antiviral activity using green fluorescent protein (GFP)-expressing H1N1 (A/PR/8/34) influenza A-infected RAW 264.7 cells. Compounds 1 and 3 exhibited significant inhibitory effects against influenza A viral infection in co-treatment conditions. In addition, compounds 1 and 3 reduced viral protein levels, including M1, M2, HA, and neuraminidase (NA), and suppressed neuraminidase (NA) activity in RAW 264.7 cells. These findings demonstrated that 2′-hydroxyl yokovanol and yokovanol, isolated from O. caudate, inhibit influenza A virus by suppressing NA activity. The moderate inhibitory activities of these flavonoids against influenza A virus suggest that they may be developed as novel anti-influenza drugs in the future. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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Review

Jump to: Editorial, Research

20 pages, 1778 KiB

Open AccessReview

Polyphenols and Visual Health: Potential Effects on Degenerative Retinal Diseases

by Pol Fernandez-Gonzalez, Aina Mas-Sanchez and Pere Garriga

Molecules 2021, 26(11), 3407; https://doi.org/10.3390/molecules26113407 - 4 Jun 2021

Cited by 12 | Viewed by 4638

Abstract

Dietary polyphenols are a group of natural compounds that have been proposed to have beneficial effects on human health. They were first known for their antioxidant properties, but several studies over the years have shown that these compounds can exert protective effects against chronic diseases. Nonetheless, the mechanisms underlying these potential benefits are still uncertain and contradictory effects have been reported. In this review, we analyze the potential effects of polyphenol compounds on some visual diseases, with a special focus on retinal degenerative diseases. Current effective therapies for the treatment of such retinal diseases are lacking and new strategies need to be developed. For this reason, there is currently a renewed interest in finding novel ligands (or known ligands with previously unexpected features) that could bind to retinal photoreceptors and modulate their molecular properties. Some polyphenols, especially flavonoids (e.g., quercetin and tannic acid), could attenuate light-induced receptor damage and promote visual health benefits. Recent evidence suggests that certain flavonoids could help stabilize the correctly folded conformation of the visual photoreceptor protein rhodopsin and offset the deleterious effect of retinitis pigmentosa mutations. In this regard, certain polyphenols, like the flavonoids mentioned before, have been shown to improve the stability, expression, regeneration and folding of rhodopsin mutants in experimental in vitro studies. Moreover, these compounds appear to improve the integration of the receptor into the cell membrane while acting against oxidative stress at the same time. We anticipate that polyphenol compounds can be used to target visual photoreceptor proteins, such as rhodopsin, in a way that has only been recently proposed and that these can be used in novel approaches for the treatment of retinal degenerative diseases like retinitis pigmentosa; however, studies in this field are limited and further research is needed in order to properly characterize the effects of these compounds on retinal degenerative diseases through the proposed mechanisms. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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24 pages, 378 KiB

Open AccessReview

Polyphenols and Fish Oils for Improving Metabolic Health: A Revision of the Recent Evidence for Their Combined Nutraceutical Effects

by Lucía Méndez and Isabel Medina

Molecules 2021, 26(9), 2438; https://doi.org/10.3390/molecules26092438 - 22 Apr 2021

Cited by 19 | Viewed by 5325

Abstract

Polyphenols and omega-3 polyunsaturated fatty acids from fish oils, i.e., eicosapentaenoic and docosahexaenoic acids, are well-recognized nutraceuticals, and their single antioxidant and anti-inflammatory properties have been demonstrated in several studies found in the literature. It has been reported that the combination of these nutraceuticals can lead to three-fold increases in glutathione peroxidase activity, two-fold increases in plasma antioxidant capacity, decreases of 50–100% in lipid peroxidation, protein carbonylation, and urinary 8-isoprotanes, as well as 50–200% attenuation of common inflammation biomarkers, among other effects, as compared to their individual capacities. Therefore, the adequate combination of those bioactive food compounds and their single properties should offer a powerful tool for the design of successfully nutritional interventions for the prevention and palliation of a plethora of human metabolic diseases, frequently diet-induced, whose etiology and progression are characterized by redox homeostasis disturbances and a low-grade of chronic inflammation. However, the certain mechanisms behind their biological activities, in vivo interaction (both between them and other food compounds), and their optimal doses and consumption are not well-known yet. Therefore, we review here the recent evidence accumulated during the last decade about the cooperative action between polyphenols and fish oils against diet-related metabolic alterations, focusing on the mechanisms and pathways described and the effects reported. The final objective is to provide useful information for strategies for personalized nutrition based on these nutraceuticals. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

21 pages, 641 KiB

Open AccessReview

(Poly)phenols in Inflammatory Bowel Disease and Irritable Bowel Syndrome: A Review

by Marilyn Hagan, Bu' Hussain Hayee and Ana Rodriguez-Mateos

Molecules 2021, 26(7), 1843; https://doi.org/10.3390/molecules26071843 - 25 Mar 2021

Cited by 24 | Viewed by 5741

Abstract

(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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20 pages, 2247 KiB

Open AccessReview

Pharmacological and Therapeutic Properties of Punica granatum Phytochemicals: Possible Roles in Breast Cancer

by Marius Alexandru Moga, Oana Gabriela Dimienescu, Andreea Bălan, Lorena Dima, Sebastian Ionut Toma, Nicușor Florin Bîgiu and Alexandru Blidaru

Molecules 2021, 26(4), 1054; https://doi.org/10.3390/molecules26041054 - 17 Feb 2021

Cited by 65 | Viewed by 9137

Abstract

Background: Pomgranate (Punica granatum) represents a high source of polyphenols with great bioavailability. The role of this fruit in the prevention and treatment of various malignant pathologies has been long time cited in both scientific and non-scientific literature, making thus important to identify its involvement in the pathophysiological processes. The treatment for breast cancer had focused on the inhibition of the mechanisms that governs the estrogen activity. These mechanisms are covered either by the antagonism of the estrogen receptor (ER) or by the inhibition of the estrogen synthesis. Our interest in identifying a bioactive compound rich in polyphenols, which induces both the antagonism of the estrogen receptor, and the inhibition of the estrogen synthesis, revealed us the pomegranate fruit and its derivatives: peel and seeds. Pomegranates’ chemical composition include many biological active substances such as flavonols, flavanols, anthocyanins, proanthocyanidins, ellagitannins and gallotannins. Materials and Methods: We performed a review of the scientific literature by using the following keywords: “pomegranate”, “breast cancer”, “Punica granatum”, “pomegranate polyphenols”. Our search was performed in the PubMed and Google Scholar databases, and it included only original research written in English from the last 20 years. None of the articles were excluded due to affiliation. A total number of 28 original papers, which mentioned the beneficial activity of pomegranate against breast cancer, were selected. Both clinical and preclinical studies were considered for this review. Results: Recent discoveries pointed out that polyphenols from Punica granatum possess strong anti-cancer activity, exhibited by a variety of mechanisms, such as anti-estrogenic, anti-proliferative, anti-angiogenetic, anti-inflammatory, and anti-metastatic. Pomegranate extracts induced cell cycle arrest in the G0/G1 phase, and induced cytotoxicity in a dose- and time-dependent manner. Moreover, several polyphenols extracted from pomegranate inhibited the invasion potential, migration and viability of breast cancer cells. The effects of pomegranate juice on serum estrogens and other sexual hormones levels were also investigated on two human cohorts. Conclusions: Punica granatum represents a promising area in oncology. The large availability and low cost, associated with the lack of side effects, made from this natural product a great strategy for the management of breast cancer. There are several mechanistic studies in mouse models and in breast cancer cell lines, suggesting the possible pathways through which polyphenols from pomegranate extracts act, but larger and better-controlled studies are necessary in the future. Only two small clinical trials were conducted on humans until now, but their results are contradictory and should be considered preliminary. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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20 pages, 2945 KiB

Open AccessReview

Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia

by Kensuke Mitsunari, Yasuyoshi Miyata, Tomohiro Matsuo, Yuta Mukae, Asato Otsubo, Junki Harada, Tsubasa Kondo, Tsuyoshi Matsuda, Kojiro Ohba and Hideki Sakai

Molecules 2021, 26(2), 450; https://doi.org/10.3390/molecules26020450 - 16 Jan 2021

Cited by 25 | Viewed by 5109

Abstract

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action. Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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21 pages, 1250 KiB

Open AccessFeature PaperReview

Flavonoids as Phytoestrogenic Components of Hops and Beer

by Tomasz Tronina, Jarosław Popłoński and Agnieszka Bartmańska

Molecules 2020, 25(18), 4201; https://doi.org/10.3390/molecules25184201 - 14 Sep 2020

Cited by 39 | Viewed by 8788

Abstract

The value of hops (Humulus lupulus L.) in beer production has been undisputed for centuries. Hops is rich in humulones and lupulones which gives the characteristic aroma and bitter taste, and preserves this golden drink against growing bacteria and molds. Besides α- and β-acids, the lupulin glands of hop cones excrete prenylated flavonoids, which exhibit a broad spectrum of biological activities and therefore has therapeutic potential in humans. Recently, interest in hops was raised due to hop prenylated flavanones which show extraordinary estrogen activities. The strongest known phytoestrogen so far is 8-prenylnaringenin (8-PN), which along with 6-prenylanaringenin (6-PN), 6,8-diprenylnaringenin (6,8-DPN) and 8-geranylnaringenin (8-GN) are fundamental for the potent estrogen activity of hops. This review provides insight into the unusual hop phytoestrogens and shows numerous health benefits associated with their wide spectrum of biological activities including estrogenic, anticancer, neuropreventive, antinflamatory, and antimicrobial properties, which were intensively studied, and potential applications of these compounds such as, as an alternative to hormone replacement therapy (HRT). Full article

(This article belongs to the Special Issue Polyphenols and Human Being: From Epidemiology to Molecular Targets)

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