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Antioxidants
Special Issues
Role of Flavonoids on Cell Signalling Pathways
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Role of Flavonoids on Cell Signalling Pathways

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (31 August 2019) | Viewed by 41385

Special Issue Editor

Dr. Christine Bosch

E-Mail Website
Guest Editor
School of Food Science and Nutrition, Faculty of Mathematics and Physical Sciences, University of Leeds, Leeds, UK
Interests: flavonoid cellular effects; oxidative stress; inflammation; NFkB and Nrf2 signalling; gene regulation; mitochondria; functional foods

Special Issue Information

Dear Colleagues,

The group of flavonoids has attracted our interest over many years; however, we are still lacking a detailed understanding of basic mechanisms to fully explain their beneficial properties. Flavonoids and some of their metabolites have been shown to affect key cell signalling pathways, demonstrating their involvement in a number of cell functions, e.g., related to redox signalling, inflammation, and metabolic regulation. Mechanisms are likely to involve direct interactions of flavonoids with proteins, including transcription factors and nuclear receptors, and their impact on gene regulatory networks as well as affinities for membrane association relating to subcellular localization and targeted effects in mitochondria or nucleus. Recent findings on the importance of gut derived flavonoid metabolites has added an additional layer to this complex topic.

This Special Issue welcomes recent original findings and reviews on the following aspects of this topic:

- Mechanistic studies on flavonoids on different cellular signalling pathways (in vitro and in vivo)

- Flavonoid-protein and receptor interactions, identification of cellular binding proteins

- Subcellular location, e.g., mitochondria interactions, and consequences for cell signalling

- Differential effects of flavonoid subgroups and their (gut) metabolites on signalling and function

- Flavonoid effects on epigenetic mechanisms

Dr. Christine Bosch
Guest Editor

Manuscript Submission Information

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

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

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

Keywords

  • Flavonoid modulation of gene expression
  • Cell signalling pathways
  • Flavonoid targets: protein/receptor interaction
  • Cellular flavonoid metabolism
  • Flavonoids and epigenetics

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Published Papers (3 papers)

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Research

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11 pages, 2070 KiB  
Article
Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression
by Seok Won Lee, Jae Heon Kim, Hyerim Song, Jin Kyung Seok, Seong Su Hong and Yong Chool Boo
Antioxidants 2019, 8(4), 87; https://doi.org/10.3390/antiox8040087 - 4 Apr 2019
Cited by 25 | Viewed by 5531
Abstract
Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to [...] Read more.
Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to examine its action mechanism, focusing on the regulation of tyrosinase (TYR) expression in cells. Cell-based assay was undertaken using murine melanoma B16-F10 cells and primary human epidermal melanocytes (HEMs). Luteolin 7-sulfate showed lower toxicity compared to luteolin in B16-F10 cells. At the non-toxic concentration ranges, luteolin 7-sulfate attenuated melanin synthesis, stimulated by α-melanocyte-stimulating hormone or forskolin. Luteolin 7-sulfate attenuated forskolin-induced microphthalmia-associated transcription factor (MITF) and TYR expressions at the mRNA and protein levels in B16-F10 cells. It also attenuated the phosphorylation of cAMP-responsive element binding protein (CREB) stimulated by forskolin. Luteolin 7-sulfate also attenuated melanin synthesis in primary HEMs. This study demonstrates that luteolin 7-sulfate attenuates TYR gene expression through the intervention of a CREB- and MITF-mediated signaling pathway, leading to the decreased melanin synthesis. Full article
(This article belongs to the Special Issue Role of Flavonoids on Cell Signalling Pathways)
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Review

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28 pages, 20285 KiB  
Review
Potential Role of Flavonoids in Treating Chronic Inflammatory Diseases with a Special Focus on the Anti-Inflammatory Activity of Apigenin
by Rashida Ginwala, Raina Bhavsar, De Gaulle I. Chigbu, Pooja Jain and Zafar K. Khan
Antioxidants 2019, 8(2), 35; https://doi.org/10.3390/antiox8020035 - 5 Feb 2019
Cited by 386 | Viewed by 25096
Abstract
Inflammation has been reported to be intimately linked to the development or worsening of several non-infectious diseases. A number of chronic conditions such as cancer, diabetes, cardiovascular disorders, autoimmune diseases, and neurodegenerative disorders emerge as a result of tissue injury and genomic changes [...] Read more.
Inflammation has been reported to be intimately linked to the development or worsening of several non-infectious diseases. A number of chronic conditions such as cancer, diabetes, cardiovascular disorders, autoimmune diseases, and neurodegenerative disorders emerge as a result of tissue injury and genomic changes induced by constant low-grade inflammation in and around the affected tissue or organ. The existing therapies for most of these chronic conditions sometimes leave more debilitating effects than the disease itself, warranting the advent of safer, less toxic, and more cost-effective therapeutic alternatives for the patients. For centuries, flavonoids and their preparations have been used to treat various human illnesses, and their continual use has persevered throughout the ages. This review focuses on the anti-inflammatory actions of flavonoids against chronic illnesses such as cancer, diabetes, cardiovascular diseases, and neuroinflammation with a special focus on apigenin, a relatively less toxic and non-mutagenic flavonoid with remarkable pharmacodynamics. Additionally, inflammation in the central nervous system (CNS) due to diseases such as multiple sclerosis (MS) gives ready access to circulating lymphocytes, monocytes/macrophages, and dendritic cells (DCs), causing edema, further inflammation, and demyelination. As the dearth of safe anti-inflammatory therapies is dire in the case of CNS-related disorders, we reviewed the neuroprotective actions of apigenin and other flavonoids. Existing epidemiological and pre-clinical studies present considerable evidence in favor of developing apigenin as a natural alternative therapy against chronic inflammatory conditions. Full article
(This article belongs to the Special Issue Role of Flavonoids on Cell Signalling Pathways)
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Other

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10 pages, 1296 KiB  
Brief Report
The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells
by Cesidio Giuliani
Antioxidants 2019, 8(5), 112; https://doi.org/10.3390/antiox8050112 - 29 Apr 2019
Cited by 96 | Viewed by 9770
Abstract
Previous studies have shown that quercetin inhibits thyroid function both in vitro and in vivo. An attempt to evaluate the effect of quercetin at the promoter level of the thyroid-specific genes led to the observation that this compound induces the basal activity of [...] Read more.
Previous studies have shown that quercetin inhibits thyroid function both in vitro and in vivo. An attempt to evaluate the effect of quercetin at the promoter level of the thyroid-specific genes led to the observation that this compound induces the basal activity of the reporter vector. Therefore, the action of quercetin has been evaluated on the basal activity of several reporter vectors: The PGL3 basic, promoter and control vectors from Promega, and a pSV-based chloramphenicol acetyltransferase (CAT) reporter vector. In the Fisher Rat Thyroid cell Line FRTL-5 thyroid cells transiently transfected, quercetin 10 μM increased the basal activity of all the reporter vectors evaluated, although the degree of the effect was significantly different among them. The analysis of the difference among the regulatory regions of these vectors identified the activator protein 1 (AP-1) binding site as one of the potential sites involved in the quercetin effect. Electromobility shift assay experiments showed that the treatment with quercetin induced the binding of a protein complex to an oligonucleotide containing the AP-1 consensus binding site. This is the first study showing an effect of quercetin on AP-1 activity in thyroid cells. Further studies are in progress to understand the role of AP-1 activation in the effects of quercetin on thyroid function. Full article
(This article belongs to the Special Issue Role of Flavonoids on Cell Signalling Pathways)
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