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Natural Antioxidants in Cell Signaling

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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 (30 June 2021) | Viewed by 23497

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Dr. Mirko Pesce

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Department of Medicine and Aging Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy
Interests: inflammation; oxidative stress; autophagy; senescence; myokines; cytokines
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Dr. Antonia Patruno

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Department of Medicine and Aging Science, University “G. D’Annunzio” Chieti-Pescara, Via dei Vestini, 31, 66100 Chieti, Italy
Interests: oxidative/nitrosative stress; cell signalling; tissue repair; neurodegenerative diseases
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Prof. Dr. Patrizia Ballerini

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1. Department of Neuroscience, Imaging and Clinical Sciences, “G. d’Annunzio” University of Chieti, 66100 Chieti, Italy
2. Center for Research on Aging and Translational Medicine (CeSI-MeT), “G. d’Annunzio” University of Chieti, 66100 Chieti, Italy
Interests: oxidative/nitrosative stress; neurodegenerative diseases
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Special Issue Information

Dear Colleagues,

During the last decade, a plethora of natural products have been identified as plant and fungal metabolites and have served as leads in drug discovery due to their efficacy, safety and selectivity. Beneficial properties have been attributed to the compounds characterized by a high antioxidant capacity and, for this reason, also referred as natural antioxidants. Nevertheless, the functional connection between natural antioxidants and the intracellular signaling machinery still remains to be well investigated.

This Special Issue of the International Journal of Molecular Sciences, “Natural Antioxidants in Cell Signaling” will include a selection of original articles and reviews aimed at expanding our awareness of the progress in the knowledge of the interplay between natural antioxidants and cell signaling, in physiological or pathological cellular models or conditions.

Dr. Mirko Pesce
Prof. Dr. Antonia Patruno
Prof. Dr. Patrizia Ballerini
Guest Editors

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Keywords

Natural antioxidants
Reactive oxygen species
Cell signaling
Kinase
Phosphatase
Transcription factor
Target identification

Published Papers (6 papers)

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Research

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13 pages, 10794 KiB

Open AccessArticle

Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration

by Vittorio Abruzzese, Ilenia Matera, Fabio Martinelli, Monica Carmosino, Prashant Koshal, Luigi Milella, Faustino Bisaccia and Angela Ostuni

Int. J. Mol. Sci. 2021, 22(8), 3871; https://doi.org/10.3390/ijms22083871 - 8 Apr 2021

Cited by 6 | Viewed by 2421

Abstract

Quercetin is a member of the flavonoid group of compounds, which is abundantly present in various dietary sources. It has excellent antioxidant properties and anti-inflammatory activity and is very effective as an anti-cancer agent against various types of tumors, both in vivo and in vitro. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family, such as P-gp, ABCC1, ABCC2, and ABCG2, and the activity of ecto-5′-nucleotidase (NT5E/CD73), a key regulator in some tumor processes such as invasion, migration, and metastasis. In this study, we investigated the effect of Quercetin on ABCC6 expression in HepG2 cells. ABCC6 is a member of the superfamily of ATP-binding cassette (ABC) transporters, poorly involved in drug resistance, whose mutations cause pseudoxanthoma elasticum, an inherited disease characterized by ectopic calcification of soft connective tissues. Recently, it has been reported that ABCC6 contributes to cytoskeleton rearrangements and HepG2 cell motility through purinergic signaling. Gene and protein expression were evaluated by quantitative Reverse-Transcription PCR (RT-qPCR) and western blot, respectively. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by an in vitro wound-healing migration assay. We propose that ABCC6 expression may be controlled by the AKT pathway as part of an adaptative response to oxidative stress, which can be mitigated by the use of Quercetin-like flavonoids. Full article

(This article belongs to the Special Issue Natural Antioxidants in Cell Signaling)

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15 pages, 1758 KiB

Open AccessArticle

The Anti-Melanogenesis Effect of 3,4-Dihydroxybenzalacetone through Downregulation of Melanosome Maturation and Transportation in B16F10 and Human Epidermal Melanocytes

by Yi-Jung Liu, Jia-Ling Lyu, Yueh-Hsiung Kuo, Chen-Yuan Chiu, Kuo-Chiang Wen and Hsiu-Mei Chiang

Int. J. Mol. Sci. 2021, 22(6), 2823; https://doi.org/10.3390/ijms22062823 - 10 Mar 2021

Cited by 11 | Viewed by 4794

Abstract

The biosynthesis pathway of melanin is a series of oxidative reactions that are catalyzed by melanin-related proteins, including tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). Reagents or materials with antioxidative or free radical-scavenging activities may be candidates for anti-melanogenesis. 3,4-Dihydroxybenzalacetone (DBL) is a polyphenol isolated from fungi, such as Phellinus obliguus (Persoon) Pilat and P. linteus. In this study, we investigated the effects and mechanisms of DBL on antioxidation and melanogenesis in murine melanoma cells (B16F10) and human epidermal melanocytes (HEMs). The results indicated that DBL scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radicals, and exhibited potent reducing power, indicating that it displays strong antioxidative activity. DBL also inhibited the expression of TYR, TRP-1, TRP-2, and microphthalmia-related transcription factor (MITF) in both the cells. In addition, DBL inhibited hyperpigmentation in B16F10 and HEMs by regulating the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA), v-akt murine thymoma viral oncogene homolog (AKT)/glycogen synthase kinase 3 beta (GSK3β), and mitogen-activated protein kinase kinase (MEK)/extracellular regulated protein kinase (ERK) signaling pathways. DBL not only shortened dendritic melanocytes but also inhibited premelanosome protein 17 (PMEL17) expression, slowing down the maturation of melanosome transportation. These results indicated that DBL promotes anti-melanogenesis by inhibiting the transportation of melanosomes. Therefore, DBL is a potent antioxidant and depigmenting agent that may be used in whitening cosmetics. Full article

(This article belongs to the Special Issue Natural Antioxidants in Cell Signaling)

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14 pages, 2422 KiB

Open AccessArticle

Resveratrol Affects Insulin Signaling in Type 2 Diabetic Goto-Kakizaki Rats

by Katarzyna Szkudelska, Marzanna Deniziak, Maciej Sassek, Ignacy Szkudelski, Wojciech Noskowiak and Tomasz Szkudelski

Int. J. Mol. Sci. 2021, 22(5), 2469; https://doi.org/10.3390/ijms22052469 - 28 Feb 2021

Cited by 10 | Viewed by 3543

Abstract

Resveratrol is a biologically active diphenolic compound exerting multiple beneficial effects in the organism, including anti-diabetic properties. This action is, however, not fully elucidated. In the present study, we examined effects of resveratrol on some parameters related to insulin signaling, and also on diabetes-associated dysregulation in Goto-Kakizaki (GK) rats with congenital type 2 diabetes. Resveratrol was given at the dose of 20 mg/kg b.w. for 10 weeks. It was shown that the expression and phosphorylation levels of insulin receptor in the skeletal muscle of GK rats were significantly decreased, compared with control animals. However, these changes were totally prevented by resveratrol. Liver expression of the insulin receptor was also reduced, but in this case, resveratrol was ineffective. Resveratrol was also demonstrated to significantly influence parameters of insulin binding (dissociation constant and binding capacity) in the skeletal muscle and liver. Moreover, it was shown that the expression levels of proteins related to intracellular glucose transport (GLUT4 and TUG) in adipose tissue of GK rats were significantly decreased. However, treatment with resveratrol completely abolished these changes. Resveratrol was found to induce normalization of TUG expression in the skeletal muscle. Blood levels of insulin and GIP were elevated, whereas proinsulin and GLP-1 diminished in GK rats. However, concentrations of these hormones were not affected by resveratrol. These results indicate that resveratrol partially ameliorates diabetes-associated dysregulation in GK rats. The most relevant finding covers the normalization of the insulin receptor expression in the skeletal muscle and also GLUT4 and TUG in adipose tissue. Full article

(This article belongs to the Special Issue Natural Antioxidants in Cell Signaling)

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17 pages, 7069 KiB

Open AccessArticle

Potential Protection Effect of ER Homeostasis of N⁶-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells

by Charng-Cherng Chyau, Huei-Lin Wu, Chiung-Chi Peng, Shiau-Huei Huang, Chin-Chu Chen, Cheng-Hsu Chen and Robert Y. Peng

Int. J. Mol. Sci. 2021, 22(4), 1577; https://doi.org/10.3390/ijms22041577 - 4 Feb 2021

Cited by 14 | Viewed by 2058

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N⁶-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK–2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex^® LH–20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK–2 cells. The HK–2 cells were pretreated with HEA (10–20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF–6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway. Full article

(This article belongs to the Special Issue Natural Antioxidants in Cell Signaling)

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16 pages, 3315 KiB

Open AccessArticle

The Effect of Cannabidiol on UV-Induced Changes in Intracellular Signaling of 3D-Cultured Skin Keratinocytes

by Agnieszka Gęgotek, Sinemyiz Atalay, Adelina Rogowska-Wrzesińska and Elżbieta Skrzydlewska

Int. J. Mol. Sci. 2021, 22(3), 1501; https://doi.org/10.3390/ijms22031501 - 2 Feb 2021

Cited by 13 | Viewed by 5012

Abstract

Human epidermal keratinocytes are constantly exposed to UV radiation. As a result, there is a significant need for safe and effective compounds to protect skin cells against this environmental damage. This study aimed to analyze the effect of phytocannabinoid-cannabinoid (CBD)-on the proteome of UVA/B irradiated keratinocytes. The keratinocytes were cultured in a three-dimensional (3D) system, designed to mimic epidermal conditions closely. The obtained results indicate that CBD protected against the harmful effects of UVA/B radiation. CBD decreased the expression of proinflammatory proteins, including TNFα/NFκB and IκBKB complex and decreased the expression of proteins involved in de novo protein biosynthesis, which are increased in UVA/B-irradiated cells. Additionally, CBD enhanced the UV-induced expression of 20S proteasome subunits. CBD also protected protein structures from 4-hydroxynonenal (HNE)-binding induced by UV radiation, which primarily affects antioxidant enzymes. CBD-through its antioxidant/anti-inflammatory activity and regulation of protein biosynthesis and degradation-protects skin cells against UVA/B-induced changes. In the future, its long-term use in epidermal cells should be investigated. Full article

(This article belongs to the Special Issue Natural Antioxidants in Cell Signaling)

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Review

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37 pages, 1987 KiB

Open AccessReview

A Review of Plant Extracts and Plant-Derived Natural Compounds in the Prevention/Treatment of Neonatal Hypoxic-Ischemic Brain Injury

by Hadi Mohsenpour, Mirko Pesce, Antonia Patruno, Azam Bahrami, Pardis Mohammadi Pour and Mohammad Hosein Farzaei

Int. J. Mol. Sci. 2021, 22(2), 833; https://doi.org/10.3390/ijms22020833 - 15 Jan 2021

Cited by 22 | Viewed by 4694

Abstract

Neonatal hypoxic-ischemic (HI) brain injury is one of the major drawbacks of mortality and causes significant short/long-term neurological dysfunction in newborn infants worldwide. To date, due to multifunctional complex mechanisms of brain injury, there is no well-established effective strategy to completely provide neuroprotection. Although therapeutic hypothermia is the proven treatment for hypoxic-ischemic encephalopathy (HIE), it does not completely chang outcomes in severe forms of HIE. Therefore, there is a critical need for reviewing the effective therapeutic strategies to explore the protective agents and methods. In recent years, it is widely believed that there are neuroprotective possibilities of natural compounds extracted from plants against HIE. These natural agents with the anti-inflammatory, anti-oxidative, anti-apoptotic, and neurofunctional regulatory properties exhibit preventive or therapeutic effects against experimental neonatal HI brain damage. In this study, it was aimed to review the literature in scientific databases that investigate the neuroprotective effects of plant extracts/plant-derived compounds in experimental animal models of neonatal HI brain damage and their possible underlying molecular mechanisms of action. Full article

(This article belongs to the Special Issue Natural Antioxidants in Cell Signaling)

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