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Polyphenols-Biological Systems Crosstalk

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 27115

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Guest Editor
Departamento de Química e Bioquímica, Universidade do Porto, Porto, Portugal
Interests: quality and food safety; polyphenols; organic chemistry; metabolomics; lypidomics; proteomics
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Special Issue Information

Dear Colleagues,

The high incidence of non-communicable diseases (NCDs) such as cancer, cardiovascular and autoimmune diseases as well as metabolic disorders has increased the awareness of consumers, who are looking for “healthy” food. Beyond nutrients, the diet provides a vast source of bioactive compounds able to modulate several biological actions in living organisms, cells or tissues. Among them, polyphenols arise as the most widely studied. A growing body of research, both in vitro and in vivo or ex vivo, have deciphered different mechanisms by which polyphenols could modulate cellular and molecular processes playing a pivotal role in the pathophysiology of targeted NCDs. However, results from clinical and observational studies are not conclusive. The chemistry of polyphenols is quite complex, and can be affected by extrinsic factors such as culinary processes. Moreover, once ingested, polyphenols can molecularly bind to cell receptors, digestive enzymes, and microbiota spread throughout all biological compartments. This journey starts promptly in the oral cavity and all these molecular interactions will influence the bioaccessibility, bioavailability and overall biological assumption of food, as well as the general biological status. These difficulties, joined with the inter-individual variability and the troubles in managing dietary interventions, clearly demonstrate the need to go beyond to a comprehensive view. The understanding of key players in the inter-individual variabilities is the basis to decipher the real function of bioactive compounds, since “one size does not fit to all”. Overall, this Special Issue is dedicated to answering these open questions from a molecular perspective, collecting articles in the field of personalized nutrition.

Dr. Rosa Perez-Gregorio
Guest Editor

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Keywords

  • polyphenol–oral cavity interactions
  • polyphenol–gut interactions
  • polyphenol–cell receptor interactions
  • polyphenol–protein interactions
  • polyphenol–microbiota interactions
  • epigenetics
  • foodomics
  • proteomics
  • metabolomics
  • nutrigenomics
  • transcriptomics
  • metagenomics
  • NCDs
  • personalized nutrition
  • dietary intervention
  • inter-individual variability
  • gut microbiota

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Published Papers (9 papers)

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Research

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16 pages, 2720 KiB  
Article
Integrative Analysis of Metabolome and Transcriptome Reveals the Mechanism of Color Formation in Yellow-Fleshed Kiwifruit
by Yun Xiong, Junya He, Mingzhang Li, Kui Du, Hangyu Lang, Ping Gao and Yue Xie
Int. J. Mol. Sci. 2023, 24(2), 1573; https://doi.org/10.3390/ijms24021573 - 13 Jan 2023
Cited by 6 | Viewed by 1939
Abstract
During the development of yellow-fleshed kiwifruit (Actinidia chinensis), the flesh appeared light pink at the initial stage, the pink faded at the fastest growth stage, and gradually changed into green. At the maturity stage, it showed bright yellow. In order to [...] Read more.
During the development of yellow-fleshed kiwifruit (Actinidia chinensis), the flesh appeared light pink at the initial stage, the pink faded at the fastest growth stage, and gradually changed into green. At the maturity stage, it showed bright yellow. In order to analyze the mechanism of flesh color change at the metabolic and gene transcription level, the relationship between color and changes of metabolites and key enzyme genes was studied. In this study, five time points (20 d, 58 d, 97 d, 136 d, and 175 d) of yellow-fleshed kiwifruit were used for flavonoid metabolites detection and transcriptome, and four time points (20 d, 97 d, 136 d, and 175 d) were used for targeted detection of carotenoids. Through the analysis of the content changes of flavonoid metabolites, it was found that the accumulation of pelargonidin and cyanidin and their respective anthocyanin derivatives was related to the pink flesh of young fruit, but not to delphinidin and its derivative anthocyanins. A total of 140 flavonoid compounds were detected in the flesh, among which anthocyanin and 76% of the flavonoid compounds had the highest content at 20 d, and began to decrease significantly at 58 d until 175 d, resulting in the pale-pink fading of the flesh. At the mature stage of fruit development (175 d), the degradation of chlorophyll and the increase of carotenoids jointly led to the change of flesh color from green to yellow, in addition to chlorophyll degradation. In kiwifruit flesh, 10 carotenoids were detected, with none of them being linear carotenoids. During the whole development process of kiwifruit, the content of β-carotene was always higher than that of α-carotene. In addition, β-cryptoxanthin was the most-accumulated pigment in the kiwifruit at 175 d. Through transcriptome analysis of kiwifruit flesh, seven key transcription factors for flavonoid biosynthesis and ten key transcription factors for carotenoid synthesis were screened. This study was the first to analyze the effect of flavonoid accumulation on the pink color of yellow-fleshed kiwifruit. The high proportion of β-cryptoxanthin in yellow-fleshed kiwifruit was preliminarily found. This provides information on metabolite accumulation for further revealing the pink color of yellow-fleshed kiwifruit, and also provides a new direction for the study of carotenoid biosynthesis and regulation in yellow-fleshed kiwifruit. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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16 pages, 1757 KiB  
Article
Evaluation of the Astragalus exscapus L. subsp. transsilvanicus Roots’ Chemical Profile, Phenolic Composition and Biological Activities
by Katalin Szabo, Floricuta Ranga, Simon Elemer, Rodica Anita Varvara, Zorita Diaconeasa, Francisc Vasile Dulf and Dan Cristian Vodnar
Int. J. Mol. Sci. 2022, 23(23), 15161; https://doi.org/10.3390/ijms232315161 - 2 Dec 2022
Cited by 2 | Viewed by 2023
Abstract
Novel and natural molecules for pharmaceutical applications are a contemporary preoccupation in science which prompts research in underexplored environments. Astragalus exscapus ssp. transsilvanicus (Schur) Nyár. (ASTRA) is a plant species endemic to Transylvania, having a very similar root system with that [...] Read more.
Novel and natural molecules for pharmaceutical applications are a contemporary preoccupation in science which prompts research in underexplored environments. Astragalus exscapus ssp. transsilvanicus (Schur) Nyár. (ASTRA) is a plant species endemic to Transylvania, having a very similar root system with that of A. membranaceus (Fisch.) Bunge, known for its health promoting properties. The present study endeavored to perform basic characterization of the ASTRA roots by proximate analysis, to investigate the fatty acid profile of the lipids extracted from the ASTRA roots, to examine the phenolic composition of the root extracts by liquid chromatography, and to evaluate the biological activities through determination of the antioxidant, antimicrobial and cytotoxic capacities of the extracts. The primary compounds found in the ASTRA roots were carbohydrates and lipids, and the fatty acid composition determined by GC-MS showed linoleic acid as preponderant compound with 31.10%, followed by palmitic, oleic and α-linolenic acids with 17.30%, 15.61% and 14.21%, respectively. The methanol extract of the ASTRA roots presented highest phenolic content, Astragaloside IV being the predominant compound with 425.32 ± 0.06 µg/g DW. The antimicrobial assay showed remarkable antimicrobial potential of the extract at a concentration of 0.356 and 0.703 mg ASTRA root powder (DW)/mL, highlighting its efficacy to inhibit S. aureus and S. epidermidis bacterial strains. Furthermore, the cell proliferation assessment showed the noteworthy proficiency of the treatment in inhibiting the proliferation of B16F10 melanoma cells. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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17 pages, 2991 KiB  
Article
Involvement of NO/cGMP Signaling Pathway, Ca2+ and K+ Channels on Spasmolytic Effect of Everlasting Flower Polyphenolic Extract (Helichrysum stoechas (L.) Moench)
by Marta Sofía Valero, Víctor López, Marta Castro, Carlota Gómez-Rincón, María Pilar Arruebo, Francisco Les and Miguel Ángel Plaza
Int. J. Mol. Sci. 2022, 23(22), 14422; https://doi.org/10.3390/ijms232214422 - 20 Nov 2022
Cited by 3 | Viewed by 1732
Abstract
Functional gastrointestinal diseases (FGID) are worldwide prevalent conditions. Pharmacological treatments can be ineffective, leading the population to turn to herbal or traditional remedies. Helichrysum stoechas (L.) Moench is a medicinal plant traditionally used in the Iberian Peninsula to treat digestive disorders, but its [...] Read more.
Functional gastrointestinal diseases (FGID) are worldwide prevalent conditions. Pharmacological treatments can be ineffective, leading the population to turn to herbal or traditional remedies. Helichrysum stoechas (L.) Moench is a medicinal plant traditionally used in the Iberian Peninsula to treat digestive disorders, but its effects on gastrointestinal motility have not been scientifically demonstrated. The aim of this work was to evaluate the antispasmodic effect of a polyphenolic extract of H. stoechas (HSM), its mechanism of action and its antioxidant activity. Isometric myography studies were performed in rat ileum, and malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) levels were measured in rat jejunum. HSM reduced the integrated mechanical activity of spontaneous contractions. In Ca2+-free medium, HSM reduced the concentration–response curve of CaCl2 similarly to verapamil. Pre-incubation with the extract blocked the contraction induced by Bay K8644, KCl and carbachol. L-NAME, ODQ, Rp-8-Br-PET-cGMPS, KT-5823, apamin, TRAM-34 and charybdotoxin reduced the relaxant effect of the extract on spontaneous contractions. MDA+4-HDA levels in LPS-treated tissue were reduced by the extract, showing antioxidant activity. In conclusion, HSM showed antispasmodic activity through inhibition of Ca2+ influx, activation of the NO/PKG/cGMP pathway and opening of Ca2+-activated K+ channels. The results suggest that H. stoechas could help in the prevention or treatment of FGIDs. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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17 pages, 1269 KiB  
Article
Dietary-Fibre-Rich Fractions Isolated from Broccoli Stalks as a Potential Functional Ingredient with Phenolic Compounds and Glucosinolates
by Vanesa Núñez-Gómez, Rocío González-Barrio, Nieves Baenas, Diego A. Moreno and Mª Jesús Periago
Int. J. Mol. Sci. 2022, 23(21), 13309; https://doi.org/10.3390/ijms232113309 - 1 Nov 2022
Cited by 7 | Viewed by 2840
Abstract
The Brassica oleracea industry generates large amounts of by-products to which value could be added because of the characteristics of their composition. The aim was to extract different fibre fractions from broccoli stalks to obtain potential new added-value ingredients. Using an ethanol and [...] Read more.
The Brassica oleracea industry generates large amounts of by-products to which value could be added because of the characteristics of their composition. The aim was to extract different fibre fractions from broccoli stalks to obtain potential new added-value ingredients. Using an ethanol and water extraction procedure, two fibre-rich fractions (total fibre fraction, TFB, and insoluble fibre fraction, IFB) were obtained. These fractions were analysed to determine the nutritional, (poly)phenols and glucosinolates composition and physicochemical properties, comparing the results with those of freeze-dried broccoli stalks (DBS). Although TFB showed a higher content of total dietary fibre, IFB had the same content of insoluble dietary fibre as TFB (54%), better hydration properties, higher content of glucosinolates (100 mg/100 g d.w.) and (poly)phenols (74.7 mg/100 g d.w.). The prebiotic effect was evaluated in IFB and compared with DBS by in vitro fermentation with human faecal slurries. After 48 h, the short-chain fatty acid (SCFA) production was higher with IFB than with DBS because of the greater presence of both uronic acids, the main component of pectin, and (poly)phenols. These results reveal that novel fibre-rich ingredients—with antioxidant, technological and physiological effects—could be obtained from broccoli stalks by using green extraction methods. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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17 pages, 1382 KiB  
Article
Effect of In Vitro Gastrointestinal Digestion on Amino Acids, Polyphenols and Antioxidant Capacity of Tamarillo Yoghurts
by Tung Thanh Diep, Michelle Ji Yeon Yoo and Elaine Rush
Int. J. Mol. Sci. 2022, 23(5), 2526; https://doi.org/10.3390/ijms23052526 - 25 Feb 2022
Cited by 19 | Viewed by 3342
Abstract
Laird’s Large tamarillo powder is high in protein (10%) essential amino acids (EAAs), gamma-aminobutyric acid (GABA) and polyphenols (0.6% phenolics plus anthocyanins) and fibre 25%. This study aimed to investigate, using a standardized static in vitro digestion model, the stability of amino acids [...] Read more.
Laird’s Large tamarillo powder is high in protein (10%) essential amino acids (EAAs), gamma-aminobutyric acid (GABA) and polyphenols (0.6% phenolics plus anthocyanins) and fibre 25%. This study aimed to investigate, using a standardized static in vitro digestion model, the stability of amino acids and antioxidant capacity of polyphenols in yoghurt fortified with 5, 10 and 15% tamarillo powder either before (PRE) or after (POS) fermentation. Compared to plain yoghurt, the fruit polyphenols (rutinosides and glycosides) were retained and substantial increases in FEAAs (free essential amino acids), total phenolic content (TPC) and antioxidant activity were observed particularly at the end of intestinal phase of digestion. Together with SDS-PAGE results, peptides and proteins in tamarillo yoghurts were more easily digested and therefore may be better absorbed in the small intestine compared to the control. TPC and antioxidant activity of fortified yoghurts increased significantly after in vitro digestion. Relatively high bioaccessibilty of chlorogenic acid and kaempferol-3-rutinoside in digested PRE samples was observed. The results suggest that the yoghurt matrix might protect some compounds from degradation, increasing bioaccessibility and in the small intestine allow increased absorption and utilization possible. Fortification would deliver intact polyphenols and fibre to the large intestine and improve gut health. Further research of acceptability, shelf life, and then trials for health effects should be implemented. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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Review

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18 pages, 957 KiB  
Review
Dietary Polyphenols and In Vitro Intestinal Fructose Uptake and Transport: A Systematic Literature Review
by Stefania Iametti, Francesco Bonomi and Mattia Di Nunzio
Int. J. Mol. Sci. 2022, 23(22), 14355; https://doi.org/10.3390/ijms232214355 - 18 Nov 2022
Cited by 7 | Viewed by 2213
Abstract
Recent evidence links chronic consumption of large amounts of fructose (FRU) with several non-communicable disease. After ingestion, dietary FRU is absorbed into the intestinal tract by glucose transporter (GLUT) 5 and transported to the portal vein via GLUT2. GLUT2 is primarily localized on [...] Read more.
Recent evidence links chronic consumption of large amounts of fructose (FRU) with several non-communicable disease. After ingestion, dietary FRU is absorbed into the intestinal tract by glucose transporter (GLUT) 5 and transported to the portal vein via GLUT2. GLUT2 is primarily localized on the basolateral membrane, but GLUT2 may be dislocated post-prandially from the basolateral membrane of intestinal cells to the apical one. Polyphenols (PP) are plant secondary metabolites that exert hypoglycemic properties by modulating intracellular insulin signaling pathways and by inhibiting intestinal enzymes and transporters. Post-prandially, PP may reach high concentrations in the gut lumen, making the inhibition of FRU absorption a prime target for exploring the effects of PP on FRU metabolism. Herein, we have systematically reviewed studies on the effect of PP and PP-rich products on FRU uptake and transport in intestinal cells. In spite of expectations, the very different experimental conditions in the various individual studies do not allow definitive conclusions to be drawn. Future investigations should rely on standardized conditions in order to obtain comparable results that allow a credible rating of polyphenols and polyphenol-rich products as inhibitors of fructose uptake. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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26 pages, 567 KiB  
Review
Nigella sativa L. and Its Active Compound Thymoquinone in the Clinical Management of Diabetes: A Systematic Review
by Mohamad Fawzi Mahomoodally, Muhammad Zakariyyah Aumeeruddy, Lesetja J. Legoabe, Domenico Montesano and Gokhan Zengin
Int. J. Mol. Sci. 2022, 23(20), 12111; https://doi.org/10.3390/ijms232012111 - 11 Oct 2022
Cited by 12 | Viewed by 3648
Abstract
Despite existing conventional hypoglycemic drugs to manage diabetes, their non-availability and cost in low-income countries coupled with the associated side effects remain a major concern. Consequently, exploring for alternative treatments to manage diabetes has been a continuous priority. Nigella sativa L. (NS) (Family: [...] Read more.
Despite existing conventional hypoglycemic drugs to manage diabetes, their non-availability and cost in low-income countries coupled with the associated side effects remain a major concern. Consequently, exploring for alternative treatments to manage diabetes has been a continuous priority. Nigella sativa L. (NS) (Family: Ranunculaceae) is regarded as a valuable traditional remedy in diabetes management and extensively studied for its biological properties. This systematic review provides a comprehensive and critical analysis of clinical studies on the efficacy, safety, and mechanism of action of NS and its compound thymoquinone (TQ) in diabetes management. The main scientific databases which were scrutinised were Scopus, PubMed, Google Scholar, and Web of Science. Data search was conducted from inception to January 2022. A total of 17 clinical studies were obtained; 16 studies on Nigella sativa L. and 1 study on its compound TQ. N. sativa was found to be highly potent in terms of its hypoglycemic activity when compared to placebo based on improvement in parameters including fasting blood glucose (FBG), postprandial blood glucose (PPBG), Hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), and homeostatic model assessment for assessment of beta-cell functionality (HOMA-β). The compound TQ in combination with a daily dose of metformin demonstrated a greater reduction in the levels of HbA1c and blood glucose compared to metformin alone. The bioavailability of TQ can be enhanced by using nanoparticulate drug delivery systems. Considering the findings of the clinical studies along with negligible adverse effects, NS has strong potential application in bioproduct development for the management of diabetes. Further investigations should explore the detailed mechanism of actions by which TQ exerts its therapeutic antidiabetic effects to provide more insights into its clinical use in the management of diabetes. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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18 pages, 1183 KiB  
Review
Novel Insights on Dietary Polyphenols for Prevention in Early-Life Origins of Hypertension: A Review Focusing on Preclinical Animal Models
by You-Lin Tain and Chien-Ning Hsu
Int. J. Mol. Sci. 2022, 23(12), 6620; https://doi.org/10.3390/ijms23126620 - 14 Jun 2022
Cited by 11 | Viewed by 2843
Abstract
Polyphenols are the largest group of phytochemicals with health benefits. Early life appears to offer a critical window of opportunity for launching interventions focused on preventing hypertension, as increasing evidence supports the supposition that hypertension can originate in early life. Although polyphenols have [...] Read more.
Polyphenols are the largest group of phytochemicals with health benefits. Early life appears to offer a critical window of opportunity for launching interventions focused on preventing hypertension, as increasing evidence supports the supposition that hypertension can originate in early life. Although polyphenols have antihypertensive actions, knowledge of the potential beneficial action of the early use of polyphenols to avert the development of hypertension is limited. Thus, in this review, we first provide a brief summary of the chemistry and biological function of polyphenols. Then, we present the current epidemiological and experimental evidence supporting the early-life origins of hypertension. We also document animal data on the use of specific polyphenols as an early-life intervention to protect offspring against hypertension in adulthood and discuss underlying mechanisms. Continued research into the use of polyphenols to prevent hypertension from starting early in life will have far-reaching implications for future health. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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50 pages, 2183 KiB  
Review
Zimbro (Juniperus communis L.) as a Promising Source of Bioactive Compounds and Biomedical Activities: A Review on Recent Trends
by Ana C. Gonçalves, José David Flores-Félix, Paula Coutinho, Gilberto Alves and Luís R. Silva
Int. J. Mol. Sci. 2022, 23(6), 3197; https://doi.org/10.3390/ijms23063197 - 16 Mar 2022
Cited by 26 | Viewed by 5093
Abstract
Plant-derived products and their extracted compounds have been used in folk medicine since early times. Zimbro or common juniper (Juniperus communis) is traditionally used to treat renal suppression, acute and chronic cystitis, bladder catarrh, albuminuria, leucorrhea, and amenorrhea. These uses are [...] Read more.
Plant-derived products and their extracted compounds have been used in folk medicine since early times. Zimbro or common juniper (Juniperus communis) is traditionally used to treat renal suppression, acute and chronic cystitis, bladder catarrh, albuminuria, leucorrhea, and amenorrhea. These uses are mainly attributed to its bioactive composition, which is very rich in phenolics, terpenoids, organic acids, alkaloids, and volatile compounds. In the last few years, several studies have analyzed the huge potential of this evergreen shrub, describing a wide range of activities with relevance in different biomedical discipline areas, namely antimicrobial potential against human pathogens and foodborne microorganisms, notorious antioxidant and anti-inflammatory activities, antidiabetic, antihypercholesterolemic and antihyperlipidemic effects, and neuroprotective action, as well as antiproliferative ability against cancer cells and the ability to activate inductive hepato-, renal- and gastroprotective mechanisms. Owing to these promising activities, extracts and bioactive compounds of juniper could be useful for the development of new pharmacological applications in the treatment of several acute and chronic human diseases. Full article
(This article belongs to the Special Issue Polyphenols-Biological Systems Crosstalk)
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