Fucoxanthin Elicits Epigenetic Modifications, Nrf2 Activation and Blocking Transformation in Mouse Skin JB6 P+ Cells

Yang, Yuqing; Cao, Mingnan; Su, Zheng‐Yuan; Wu, Renyi; Guo, Yue; Fang, Mingzhu; Kong, Ah Ng Tony

doi:10.1208/s12248-018-0197-6

Cited by 51 publications

(38 citation statements)

References 67 publications

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“…An in vitro study has elicited the antioxidant activity of FX by enhancing the Akt/Nrf2/GSH pathways in human keratinocytes [ 11 ]. Moreover, FX has been recently shown to be able to activate Nrf2 signalling pathway by inducing demethylation of CpG sites in Nrf2 [ 49 ]. In accordance with these results, our data reported that FX and BC offer a similar protection against oxidative stress caused by UVB exposure via increase of Nrf2 expression and its downstream target HO-1.…”

Section: Discussionmentioning

confidence: 99%

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

et al. 2018

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Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation.

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Section: Discussionmentioning

confidence: 99%

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

et al. 2018

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“…Studies have demonstrated that DNA demethylation and histone (de)acetylation can trigger or increase Nrf2 expression. Natural compounds derived from plants (such as sulforaphane, corosolic acid, taxifolin, reserpine, quercetin, Z-ligustilide and curcumin) and marine constituents (fucoxanthin) have been shown to activate Nrf2 signaling through epigenetic regulation ( Khor et al, 2011 ; Su et al, 2013 ; Liu et al, 2015 ; Hong et al, 2016 ; Muta et al, 2016 ; Kuang et al, 2017 ; Jie et al, 2018 ; Yang et al, 2018c ; Zhao F. et al, 2018 ). Quercetin, a natural flavonoid, significantly inhibited nickel-induced inflammation in mouse liver by decreasing Nrf2 DNA methylation and inhibiting the p38 MAPK signaling pathway ( Liu et al, 2015 ).…”

Section: Molecular Mechanisms Of Cardioprotective Natural Products Tamentioning

confidence: 99%

The Role of Natural Products in Targeting Cardiovascular Diseases via Nrf2 Pathway: Novel Molecular Mechanisms and Therapeutic Approaches

et al. 2018

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Cardiovascular diseases (CVDs) are closely linked to cellular oxidative stress and inflammation. This may be resulted from the imbalance generation of reactive oxygen species and its role in promoting inflammation, thereby contributing to endothelial dysfunction and cardiovascular complications. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a significant role in regulating expression of antioxidant and cytoprotective enzymes in response to oxidative stress. Natural products have emerged as a potential source of bioactive compounds which have shown to protect against atherogenesis development by activating Nrf2 signaling. This review aims to provide a comprehensive summary of the published data on the function, regulation and activation of Nrf2 as well as the molecular mechanisms of natural products in regulating Nrf2 signaling. The beneficial effects of using natural bioactive compounds as a promising therapeutic approach for the prevention and treatment of CVDs are reviewed.

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“…This carotenoid was found to activate Nrf2 signaling by causing demethylation of CpG islands in the Nfe2l2 promoter, resulting in inhibition of TPA-induced transformation of JB6 P+ cells. Mechanistically, fucoxanthin decreased Dnmt1 mRNA and proteins levels, but was not found to alter Hdac expression levels [85].…”

Section: Fucoxanthinmentioning

confidence: 85%

Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals

Bhattacharjee

Dashwood

2020

Antioxidants

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Epigenetics has provided a new dimension to our understanding of nuclear factor erythroid 2–related factor 2/Kelch-like ECH-associated protein 1 (human NRF2/KEAP1 and murine Nrf2/Keap1) signaling. Unlike the genetic changes affecting DNA sequence, the reversible nature of epigenetic alterations provides an attractive avenue for cancer interception. Thus, targeting epigenetic mechanisms in the corresponding signaling networks represents an enticing strategy for therapeutic intervention with dietary phytochemicals acting at transcriptional, post-transcriptional, and post-translational levels. This regulation involves the interplay of histone modifications and DNA methylation states in the human NFE2L2/KEAP1 and murine Nfe2l2/Keap1 genes, acetylation of lysine residues in NRF2 and Nrf2, interaction with bromodomain and extraterminal domain (BET) acetyl “reader” proteins, and non-coding RNAs such as microRNA (miRNA) and long non-coding RNA (lncRNA). Phytochemicals documented to modulate NRF2 signaling act by reversing hypermethylated states in the CpG islands of NFE2L2 or Nfe2l2, via the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), through the induction of ten-eleven translocation (TET) enzymes, or by inducing miRNA to target the 3′-UTR of the corresponding mRNA transcripts. To date, fewer than twenty phytochemicals have been reported as NRF2 epigenetic modifiers, including curcumin, sulforaphane, resveratrol, reserpine, and ursolic acid. This opens avenues for exploring additional dietary phytochemicals that regulate the human epigenome, and the potential for novel strategies to target NRF2 signaling with a view to beneficial interception of cancer and other chronic diseases.

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Fucoxanthin Elicits Epigenetic Modifications, Nrf2 Activation and Blocking Transformation in Mouse Skin JB6 P+ Cells

Cited by 51 publications

References 67 publications

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

Fucoxanthin-Containing Cream Prevents Epidermal Hyperplasia and UVB-Induced Skin Erythema in Mice

The Role of Natural Products in Targeting Cardiovascular Diseases via Nrf2 Pathway: Novel Molecular Mechanisms and Therapeutic Approaches

Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals

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