Cytoprotective effects of esculetin against oxidative stress are associated with the upregulation of Nrf2-mediated NQO1 expression via the activation of the ERK pathway

Han, Min; Park, Cheol; Lee, Dae‐Sung; Hong, Su‐Hyun; Choi, Il‐Whan; Kim, Gi‐Young; Choi, Sung Hyun; Shim, Jung‐Hyun; Chae, Jung‐Il; Yoo, Young Hyun; Choi, Yung Hyun

doi:10.3892/ijmm.2016.2834

Cited by 41 publications

(30 citation statements)

References 44 publications

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“…36 As a detoxifiying enzyme, NQO1 catalyzes the 2-electron reductive metabolism and detoxification of quinies, protecting cells from oxidative stress-induced injury. 37 Indeed, in the current study, the Nrf2 nuclear translocation was found to be inhibited in AGEs-exposed aorta. After treatment of matrine-type alkaloids, the nuclear translocation of Nrf2 increased dramatically.…”

Section: Discussionsupporting

confidence: 47%

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Liu

Zhang

et al. 2017

JAHA

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BackgroundThe matrine‐type alkaloids are bioactive components extracted from Sophora flavescens, which is used in treatment of diabetes mellitus in traditional Chinese medicine. Advanced glycation end products mediate diabetic vascular complications. This study was aimed to investigate the protective effects and molecular mechanisms of matrine‐type alkaloids on advanced glycation end products–induced reactive oxygen species–mediated endothelial apoptosis.Methods and ResultsRats aorta and cultured rat aortic endothelial cells were exposed to advanced glycation end products. Matrine‐type alkaloids, p38 mitogen‐activated protein kinase (MAPK) inhibitor, and small interference RNAs against p38 MAPK kinases MAPK kinase kinase (MKK)3 and MKK6 were administrated. Intracellular reactive oxygen species production, cell apoptosis, phosphorylation of MKKs/p38 MAPK, and expression levels of heme oxygenase/NADPH quinone oxidoreductase were assessed. The nuclear factor erythroid 2‐related factor 2 nuclear translocation and the binding activity of nuclear factor erythroid 2‐related factor 2 with antioxidant response element were also evaluated. Matrine‐type alkaloids suppressed intracellular reactive oxygen species production and inhibited endothelial cell apoptosis in vivo and in vitro by recovering phosphorylation of MKK3/6 and p38 MAPK, nuclear factor erythroid 2‐related factor 2 nuclear translocation, and antioxidant response element binding activity, as well as the expression levels of heme oxygenase/NADPH quinone oxidoreductase. p38 MAPK inhibitor treatment impaired the effects of matrine‐type alkaloids in vivo and in vitro. MKK3/6 silencing impaired the effects of matrine‐type alkaloids in vitro.ConclusionsMatrine‐type alkaloids exert endothelial protective effects against advanced glycation end products induced reactive oxygen species–mediated apoptosis by targeting MKK3/6 and enhancing their phosphorylation.

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Section: Discussionsupporting

confidence: 47%

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Liu

Zhang

et al. 2017

JAHA

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“…Sen et al demonstrated the role of esculetin in attenuating the progression of diabetic nephropathy via Nrf2 activation and inhibition of HGinduced ROS production [166]. Han et al reported that esculetin protected against H 2 O 2 -induced ROS accumulation in the myoblasts through the activation of the Nrf2/NQO1 pathway [167]. Treatment of the pancreatic cancer cell lines with esculetin resulted in significant inhibition of cell proliferation, intracellular ROS, and protein levels of NF-κB [168].…”

Section: Urolithin Amentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

157

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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“…3 ). Furthermore, NDRG2 alleviation of photoreceptor oxidative stress resulted in restriction of the stimulated photoreceptor antioxidant defense responses under damaging conditions, as shown by inhibited mRNA expression levels of the antioxidant master transcription factor Nuclear factor E2-related factor 2 (Nrf2) 31 and the regulated antioxidant genes Heme oxygenase-1 (Ho-1) 32 and NAD(P)H:quinone oxidoreductase-1 (Nqo-1) 33 (Fig. 5k, l ).…”

Section: Resultsmentioning

confidence: 97%

NDRG2 suppression as a molecular hallmark of photoreceptor-specific cell death in the mouse retina

Sui

Wang

et al. 2018

Cell Death Discov.

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Photoreceptor cell death is recognized as the key pathogenesis of retinal degeneration, but the molecular basis underlying photoreceptor-specific cell loss in retinal damaging conditions is virtually unknown. The N-myc downstream regulated gene (NDRG) family has recently been reported to regulate cell viability, in particular NDRG1 has been uncovered expression in photoreceptor cells. Accordingly, we herein examined the potential roles of NDRGs in mediating photoreceptor-specific cell loss in retinal damages. By using mouse models of retinal degeneration and the 661 W photoreceptor cell line, we showed that photoreceptor cells are indeed highly sensitive to light exposure and the related oxidative stress, and that photoreceptor cells are even selectively diminished by phototoxins of the alkylating agent N-Methyl-N-nitrosourea (MNU). Unexpectedly, we discovered that of all the NDRG family members, NDRG2, but not the originally hypothesized NDRG1 or other NDRG subtypes, was selectively expressed and specifically responded to retinal damaging conditions in photoreceptor cells. Furthermore, functional experiments proved that NDRG2 was essential for photoreceptor cell viability, which could be attributed to NDRG2 control of the photo-oxidative stress, and that it was the suppression of NDRG2 which led to photoreceptor cell loss in damaging conditions. More importantly, NDRG2 preservation contributed to photoreceptor-specific cell maintenance and retinal protection both in vitro and in vivo. Our findings revealed a previously unrecognized role of NDRG2 in mediating photoreceptor cell homeostasis and established for the first time the molecular hallmark of photoreceptor-specific cell death as NDRG2 suppression, shedding light on improved understanding and therapy of retinal degeneration.

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Cytoprotective effects of esculetin against oxidative stress are associated with the upregulation of Nrf2-mediated NQO1 expression via the activation of the ERK pathway

Cited by 41 publications

References 44 publications

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Matrine‐Type Alkaloids Inhibit Advanced Glycation End Products Induced Reactive Oxygen Species‐Mediated Apoptosis of Aortic Endothelial Cells In Vivo and In Vitro by Targeting MKK3 and p38MAPK Signaling

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

NDRG2 suppression as a molecular hallmark of photoreceptor-specific cell death in the mouse retina

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