Hydrolyzed Methylhesperidin Induces Antioxidant Enzyme Expression via the Nrf2–ARE Pathway in Normal Human Epidermal Keratinocytes

Kuwano, Tetsuya; Watanabe, Manabu; Kagawa, D; Murase, Takatoshi

doi:10.1021/acs.jafc.5b01992

Cited by 13 publications

(11 citation statements)

References 29 publications

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“…Kuwano et al . supported these studies by investigating the antioxidant properties of methylhesperidin (MHES), which is derived from the Citrus flavanone hesperidin and which could be hydrolyzed by gut microflora. Hydrolyzed MHES promotes Nrf2 nuclear translocation and the expression of cytoprotective genes in normal human epidermal kerationcytes, increases intracellular glutathione levels and phosphorylation of p38 MAPK, and reduces UVB‐induced ROS.…”

Section: Biological Properties Of Citrus Flavanonesmentioning

confidence: 99%

“…There is good evidence to suggest that naringenin exhibits antineuroinflammatory action inhibiting iNOS expression, NO production, p38 phosphorylation, and downstreaming STAT‐1 in neuronal glial cultures . Esmaeili and Alilou demonstrated that naringenin attenuates CCl 4 ‐induced hepatic inflammation, downregulating the activation of TNF‐α and activating the nuclear translocation of Nrf2, as previously reported . Recently, Bodduluru et al .…”

Section: Biological Properties Of Citrus Flavanonesmentioning

confidence: 99%

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Flavanones: Citrus phytochemical with health‐promoting properties

et al. 2017

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Citrus fruit and juices represent one of the main sources of compounds with a high potential for health promoting properties. Among these compounds, flavanones (such as hesperetin, naringenin, eriodictyol, isosakuranetin, and their respective glycosides), which occur in quantities ranging from ∼180 to 740 mg/L (depending on the Citrus species and cultivar) are responsible for many biological activities. These compounds support and enhance the body's defenses against oxidative stress and help the organism in the prevention of cardiovascular diseases, atherosclerosis, and cancer. Moreover, among other properties, they also show anti-inflammatory, antiviral, and antimicrobial activities. This review analyzes the biochemistry, pharmacology, and biology of Citrus flavanones, emphasizing the occurrence in Citrus fruits and juices and their bioavailability, structure-function correlations and ability to modulate signal cascades both in vitro and in vivo. © 2017 BioFactors, 43(4):495-506, 2017.

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Section: Biological Properties Of Citrus Flavanonesmentioning

confidence: 99%

Section: Biological Properties Of Citrus Flavanonesmentioning

confidence: 99%

Flavanones: Citrus phytochemical with health‐promoting properties

et al. 2017

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“…Any change in redox potential is sensed by Keap1 and results in the release of Nrf2 from the complex and its translocation to the nucleus (Jaramillo and Zhang, ). In the nucleus, Nrf2 binds to the ARE DNA sequence and activates the transcription of antioxidant genes such as haeme oxygenase‐1 and glutamate cysteine ligase catalytic subunit (Kuwano et al ., ). Nrf2 is a part of a redox signalling pathway that maintains cellular homeostasis and contributes to adaptation to OS.…”

Section: Lpo End‐products and Redox Signallingmentioning

confidence: 99%

Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

Gašparović

Žarković

et al. 2017

British J Pharmacology

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The concept of oxidative stress (OS) that connects altered redox biology with various diseases was introduced 30 years ago and has generated intensive research over the past two decades. Whereas it is now commonly accepted that macromolecule oxidation in response to ROS is associated with a variety of pathologies, the emergence of NO as a key regulator of redox signalling has led to the discovery of the pathophysiological significance of reactive nitrogen species (RNS). RNS can elicit various modifications of macromolecules and lead to nitrative or nitro-OS. In order to investigate oxidative and nitro-OS in human and in live animal models, circulating biomarker assays have been developed. This article provides an overview of key biomarkers used to assess lipid peroxidation and NO/NO 2 signalling, thereby stressing the necessity to analyse several OS biomarkers in relation to the overall (aerobic) metabolism and health condition of patients. In addition, the potential interest of heart rate variability as the non-invasive integrative biomarker of OS is discussed. LINKED ARTICLESThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc Abbreviations 4-HNE, trans-4-hydroxy-2-nonenal; ACR, acrolein; ALE, advanced lipoxidation end-products; DNP, 2,4-dinitrophenylhydrazine; FRR, free radical reaction; HRV, heart rate variability; LO, lipid alkoxyl radical; LOO, lipid peroxyl radical; LOOH, lipid hydroperoxide; LPO, lipid peroxidation; MDA, malondialdehyde; NO + , nitrosonium ion; Nrf2, Nuclear factor (erythroid-derived 2)-like 2; OMP, oxidatively modified protein; OS, oxidative stress; PUFA, polyunsaturated fatty acids; RNS, reactive nitrogen species; TBARS, thiobarbituric acid reactive substances; UPR, unfolded protein response IntroductionOxidative stress (OS), which was first introduced as a concept in redox biology and medicine in 1985 by Helmut Sies and Enrique Cadenas (Cadenas and Sies, 1985;Sies and Cadenas, 1985), has gained increasing interest over the years to become a major field of investigation in chemistry, life sciences and medicine.This concept connects oxidative chemistry with biological stress responses. However, it has the disadvantage of concealing redox chemistry, which plays a key role in cell homeostasis and signalling and in physiology, which is, for a large part, dependent on both oxidation and reduction reactions (Frein et al., 2005). This complex field of biochemistry, which plays a key role in the regulation of a variety of enzymes involved in essential signalling pathways, is now referred to as 'redox signalling' (Ullrich and Kissner, 2006) (Figure 1 et al., 2015). This reaction gives rise to peroxynitrite (ONOO À ), which is a highly reactive nitrogen species (RNS), producing nitration and nitrosation of substrates, often proteins that play important pathophysiological roles (Ullrich and Kissner, 2006;Schulz et al., 2008;Bottari, 20...

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“…Thus, the Nrf2 pathway, which controls functionality, is extremely significant. Indeed, various Nrf2 activators displayed their ability to stimulate the Nrf2 pathway in keratinocytes, leading to an impressive antioxidant protective effect [40-42]. Thus, SK-119 can be used in dermatological applications.…”

Section: Resultsmentioning

confidence: 99%

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

Kahremany

Babaev

Gvirtz

et al. 2019

Skin Pharmacol Physiol

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Background/Aims: The Nrf2 signaling pathway plays a pivotal role in neutralizing excess reactive oxygen species formation and therefore enhancing the endogenous cellular protection mechanism. Thus, activating this pathway may provide therapeutic options against oxidative stress-related disorders. We have recently applied a computer-aided drug design approach to the design and synthesis of novel Nrf2 enhancers. The current study was aimed at investigating the potential beneficial impact of (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) in skin oxidative damage models. Methods: SK-119, tested initially in PC-12 cells, attenuated oxidative stress-induced cytotoxicity concomitantly with Nrf2 activation. The potential impact of this compound was evaluated in skin-based disease models both in vitro (HaCaT cells) and ex vivo (human skin organ culture). Results: The data clearly showed the marked anti-inflammatory and photoprotection properties of the compound; SK-119-treated cells or tissues displayed a reduction in cytokine secretion induced by lipopolysaccharides (LPS) in a manner comparable with dexamethasone. In addition, topical application of SK-119 was able to block UVB-induced oxidative stress and attenuated caspase-mediated apoptosis, DNA adduct formation, and the concomitant cellular damage. Conclusion: These results indicate that SK-119 is an Nrf2 activator that can be used as a prototype molecule for the development of novel treatments of dermatological disorders related to oxidative stress.

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Hydrolyzed Methylhesperidin Induces Antioxidant Enzyme Expression via the Nrf2–ARE Pathway in Normal Human Epidermal Keratinocytes

Cited by 13 publications

References 29 publications

Flavanones: Citrus phytochemical with health‐promoting properties

Flavanones: Citrus phytochemical with health‐promoting properties

Biomarkers of oxidative and nitro‐oxidative stress: conventional and novel approaches

Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage

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