Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes

Hewage, Susara Ruwan Kumara Madduma; Piao, Mei Jing; Kang, Kyoung Ah; Ryu, Yea Seong; Fernando, Pattage Madushan Dilhara Jayatissa; Oh, Min Chang; Park, Jeong Eon; Shilnikova, Kristina; Moon, Yu Jin; Shin, Dae O; Hyun, Jin Won

doi:10.4062/biomolther.2016.112

Cited by 32 publications

(18 citation statements)

References 25 publications

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“…Galangin, a flavonoid compound with antioxidant capacity, is an active pharmacological component from propolis and Alpinia officinarum . Galangin has been reported to have anticancer and antioxidative properties . Our study demonstrated that galangin had antioxidative and anti‐inflammatory activity and promoted cell survival and collagen formation ability in HS68 dermal fibroblasts (Figure ).…”

Section: Discussionmentioning

confidence: 53%

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Galangin suppresses H₂O₂‐induced aging in human dermal fibroblasts

Chen

Weng

et al. 2017

Environmental Toxicology

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Human skin aging is a progressive process that includes intrinsic aging and extrinsic photodamage, both of which can cause an accumulation of reactive oxygen species (ROS), resulting in dermal fibrosis dysfunction and wrinkle formation. Galangin is a flavonoid that exhibits anti-inflammatory and antioxidative potential. Previous studies have reported that galangin has antioxidative activity against ROS-mediated stress. The aim of the present study is to determine the antiaging effects of galangin on dermal fibroblasts exposed to H O . In this study, we established a hydrogen peroxide-induced inflammation and aging model using human HS68 dermal fibroblasts. Stimulation of fibroblasts with H O is associated with skin aging and increased expression of inflammation-related proteins, along with downregulation of collagen I/III formation and expression of antioxidative proteins. Galangin effectively reduced NF-κB activation, the expression of inflammation-related proteins and cell aging. Galangin also reversed H O -activated cell senescence in HS68 cells. Our results reveal that galangin protects human dermal fibroblasts by inhibiting NF-κB activation, decreases the expression of inflammatory factors and upregulates IGF1R/Akt-related proteins, indicating that galangin may be a potential candidate for developing natural antiaging products that protect skin from damage caused by ROS.

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Section: Discussionmentioning

confidence: 53%

“…Previous studies have reported that galangin protects human keratinocytes against ultraviolet B (UVB)‐induced oxidative damage by activating ERK/Akt‐Nrf2 signaling . Galangin was also found to elicit anti‐inflammatory effects by inhibiting NF‐κB p65 phosphorylation in LPS‐activated RAW 264.7 cells .…”

Section: Resultsmentioning

confidence: 99%

Galangin suppresses H₂O₂‐induced aging in human dermal fibroblasts

Chen

Weng

et al. 2017

Environmental Toxicology

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“…Biochemical experiments indicated that knockdown of NRF2 could increase MDA concentration and decrease concentration of SOD, GSH and CAT, enhancing the effects of laminarin in MRC-5 cells. Numerous studies have proved the protective role of NRF2 against oxidation in various cell types, keratinocytes ( Madduma Hewage et al, 2016 ; Zheng et al, 2014 ), pancreatic β-cells ( Dinić et al, 2016 ), mesenchymal stem cells ( Loseva et al, 2012 ), amongst others, elevating SOD, GSH and CAT cellular concentration. Besides, up-regulation of NRF2 was accompanied with suppressed MDA level during the amelioration of oxidative damage ( Xie et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Lü

Liu

Zhai

et al. 2017

PeerJ

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Oxidative damage is a major cause of lung diseases, including pulmonary fibrosis. Laminarin is a kind of polysaccharide extracted from brown algae and plays vital roles in various biological processes. However, the functions and mechanisms of laminarin in pulmonary oxidative damage are poorly understood. This study aimed at investigating the protective effect of laminarin against pulmonary oxidative damage and underlying mechanisms. Human lung fibroblasts MRC-5 cells were treated with hydrogen peroxide to induce oxidative damage. Laminarin treatment was performed before or after hydrogen peroxide treatment, and then major indexes of oxidative damage, including superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH) and catalase (CAT), were quantified by biochemical assays. The expression of oxidation-related factor, nuclear factor erythroid 2 like 2 (NRF2) was analyzed by qPCR, Western blot and immunofluorescence assay. NRF2 knockdown and overexpression were performed by cell transfection to reveal possible mechanisms. Results showed that laminarin treatment of 0.020 mg/mL for 24 h, especially the pre-treatment, could significantly relieve changes in SOD, MDA, GSH and CAT that were altered by hydrogen peroxide, and promote NRF2 mRNA (P < 0.001). NRF2 protein was also elevated by laminarin, and nuclear translocation was observed. Factors in NRF2 signaling pathways, including KEAP1, NQO1, GCLC and HO1, were all regulated by laminarin. Roles of NRF2 were tested, suggesting that NRF2 regulated the concentration of SOD, MDA, GSH and CAT, suppressed KEAP1, and promoted NQO1, GCLC and HO1. These findings suggested the protective role of laminarin against pulmonary oxidative damage, which might involve the regulation of NRF2 signaling pathways. This study provided information for the clinical application of laminarin to pulmonary diseases like pulmonary fibrosis.

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“…HO-1 silencing RNAs reversed the cytoprotective, antioxidant, and anti-inflammatory effects of fisetin. Galangin was shown to protect human keratinocytes by activating ERK/Akt/Nrf2, leading to elevated expression of glutathione-synthesizing enzymes, such as γ-GCLC and glutathione synthetase [ 103 ]. Baicalein from Scutellaria baicalensis inhibited H 2 O 2 -induced cytotoxicity and apoptosis in human vitiligo melanocytes (PIG3V) by promoting Nrf2 nuclear translocation, and the expression of Nrf2 and HO-1 [ 104 ].…”

Section: Plant-derived Natural Nrf2 Modulators For Skin Protectionmentioning

confidence: 99%

Natural Nrf2 Modulators for Skin Protection

Boo

2020

Antioxidants

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Since the discovery of antioxidant responsive elements (ARE), which are commonly found in the promoter of the Phase II metabolism/antioxidant enzymes, and nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor that binds to ARE, the study conducted in this field has expanded remarkably over the decades, and the Nrf2-mediated pathway is now recognized to occupy a central position in cell defense mechanisms. Induction of the Phase II metabolism/antioxidant enzymes through direct activation of Nrf2 can be a promising strategy for preventing degenerative diseases in general, but a dark side of this strategy should be considered, as Nrf2 activation can enhance the survival of cancer cells. In this review, we discuss the historical discovery of Nrf2 and the regulatory mechanism of the Nrf2-mediated pathway, focusing on the interacting proteins and post-translational modifications. In addition, we discuss the latest studies that examined various natural Nrf2 modulators for the protective roles in the skin, in consideration of their dermatological and cosmetic applications. Studies are reviewed in the order of time of research as much as possible, to help understand how and why such studies were conducted under the circumstances of that time. We hope that this review can serve as a steppingstone in conducting more advanced research by providing a scientific basis for researchers newly entering this field.

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Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes

Cited by 32 publications

References 25 publications

Galangin suppresses H₂O₂‐induced aging in human dermal fibroblasts

Galangin suppresses H₂O₂‐induced aging in human dermal fibroblasts

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Natural Nrf2 Modulators for Skin Protection

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Galangin Activates the ERK/AKT-Driven Nrf2 Signaling Pathway to Increase the Level of Reduced Glutathione in Human Keratinocytes

Cited by 32 publications

References 25 publications

Galangin suppresses H2O2‐induced aging in human dermal fibroblasts

Galangin suppresses H2O2‐induced aging in human dermal fibroblasts

Laminarin protects against hydrogen peroxide-induced oxidative damage in MRC-5 cells possibly via regulating NRF2

Natural Nrf2 Modulators for Skin Protection

Contact Info

Product

Resources

About

Galangin suppresses H₂O₂‐induced aging in human dermal fibroblasts

Galangin suppresses H₂O₂‐induced aging in human dermal fibroblasts