Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications

Kuang, Hai‐Xue; Tang, Zhenqiu; Zhang, Chengyue; Wang, Zhibin; Li, Wenji; Yang, Chunjuan; Wang, Qiuhong; Yang, Bing‐You; Kong, Ah Ng Tony

doi:10.3390/ijms18071546

Cited by 48 publications

(35 citation statements)

References 47 publications

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“…Previous studies ( Guo et al, 2015 ; Kuang et al, 2017 ; Xie et al, 2017 ) have shown taxifolin exhibits significant antioxidant properties, it can inhibit ROS production in many kinds of cells. ROS are involved in osteoclast activation and bone loss stimulated by increased expression of RANKL, ROS could act as the intracellular secondary messengers in RANKL-induced osteoclastogenesis signaling pathways, and osteoclast differentiation can be inhibited by scavenging ROS ( Lee et al, 2005 ).…”

Section: Discussionmentioning

confidence: 95%

Effects of Taxifolin on Osteoclastogenesis in vitro and in vivo

et al. 2018

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Osteoporosis is a highly prevalent disease which has been a major public health problem and considered to be associated with chronic low-grade systemic inflammation and oxidative damage. Taxifolin is a natural flavonoid and possesses many pharmacological activities including antioxidant and anti-inflammatory. Because flavonoids have been confirmed to fight osteoporosis and promote bone health, the aim of this study was to investigate the effects of taxifolin on the formation and function of osteoclast. In this study, we examined the effects of taxifolin on osteoclast using both in vitro and in vivo studies. Taxifolin suppressed the activation of nuclear factor-κB, C-Fos and mitogen-activated protein kinase, and also decreased osteoclast-specific genes expression, including Trap, Mmp-9, Cathepsin K, C-Fos, Nfatc1, and Rank. Taxifolin also prevented reactive oxygen species (ROS) production following RANKL stimulation. In addition, taxifolin alleviated ovariectomized-induced bone loss by repressing osteoclast activity and decreasing serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and receptor activator of nuclear factor-κB ligand (RANKL) in vivo. Our results indicated that taxifolin inhibits osteoclastogenesis via regulation of modulation of several RANKL signaling pathways. Therefore, taxifolin may be considered as a potential alternative therapeutic agent for treating osteoclast-related diseases.

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Section: Discussionmentioning

confidence: 95%

Effects of Taxifolin on Osteoclastogenesis in vitro and in vivo

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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“…Bisulfite sequencing showed that the flavonoid reduced the proportion of methylated CpG sites in the Nfe2l2 promoter. At the molecular level, the protein expression levels of Dnmt1, Dnmt3a Dnmt3b, Hdac1, Hdac3, and Hdac8 were significantly decreased by taxifolin [97].…”

Section: Taxifolinmentioning

confidence: 96%

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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Taxifolin Activates the Nrf2 Anti-Oxidative Stress Pathway in Mouse Skin Epidermal JB6 P+ Cells through Epigenetic Modifications

Cited by 48 publications

References 47 publications

Effects of Taxifolin on Osteoclastogenesis in vitro and in vivo

Effects of Taxifolin on Osteoclastogenesis in vitro and in vivo

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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