Lonchocarpine Increases Nrf2/ARE-Mediated Antioxidant Enzyme Expression by Modulating AMPK and MAPK Signaling in Brain Astrocytes

Jeong, Yeon Hui; Park, Jin-Sun; Kim, Dong Hyun; Kim, Hee Sun

doi:10.4062/biomolther.2016.141

Cited by 41 publications

(28 citation statements)

References 34 publications

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“…Nrf2 plays an important role in the up-regulation of antioxidant and detoxifying enzymes. Recent studies have shown that failure of the Nrf2 function promotes carcinogen-induced DNA damage and tumor formation [ 7 , 25 ]. Therefore, Nrf2 is an important molecular target for cancer prevention [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes

et al. 2017

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A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of glutathione-related enzymes and the cell survival of human keratinocytes (HaCaT cells) was investigated. BDB treatment increased the protein and mRNA levels of glutathione synthesizing enzymes and enhanced the production of reduced glutathione in HaCaT cells. Furthermore, BDB activated NF-E2-related factor 2 (Nrf2) and promoted its localization into the nucleus by phosphorylating its up-stream signaling proteins, extracellular signal–regulated kinase and protein kinase B. Thus, BDB increased the production of reduced glutathione and established cellular protection against oxidative stress via an Nrf2-mediated pathway.

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Section: Discussionmentioning

confidence: 99%

3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes

et al. 2017

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“…Nrf2 protein reduces oxidative stress. Nrf2/ARE signaling pathway reported for its neuroprotective effect on the basis of anti-oxidant and anti-inflammatory activity [6].…”

Section: Introductionmentioning

confidence: 99%

Vorinostat: a histone deacetylases (HDAC) inhibitor ameliorates traumatic brain injury by inducing iNOS/Nrf2/ARE pathway

Xu¹,

Shi²,

Zhang³

et al. 2018

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The present investigation evaluates the protective effect of vorinostat on neuronal cells in the traumatic brain injury (TBI) and also postulates the possible mechanism of its action. Marmarou's weight-drop model was used to induce the TBI. Further, animals were treated with vorinostat 100 mg/kg intraperitoneally 30 min before the TBI induction. Neurological score and brain water content were determined in all the groups and thereafter oxidative stress parameters and adenosine triphosphate (ATP) content were determined in the neuronal tissues of TBI mice. Western blot assay and reverse transcription polymerase chain reaction (RT-PCR) was performed for the determination of the expression of several proteins in the neuronal tissues. Moreover, immunohistochemical staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was also done on the neuronal tissues of TBI mice. Data of the study reveal that treatment with vorinostat significantly reduces the altered level of grip test scores and water content in the brain of traumatic injured mice. Moreover, the altered level of oxidative stress parameters, translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and ATP content was attenuated by treating TBI mice with vorinostat. Also treatment with vorinostat ameliorates the altered expression of p-Akt, NF-κB, iNOS and caspase by the western blot assay in the neuronal tissue of TBI mice and mRNA level of HO-1 and NQO-1 significantly enhanced in vorinostat compared to the negative control group. Furthermore, the TUNEL assay also reveals that the apoptosis of neuronal cells was significantly (p < 0.01) reduced in the vorinostat-treated group compared to the negative control group. The present study concludes that vorinostat protects the neuronal injury in TBI mice by reducing the altered level of oxidative stress and inflammatory response.

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“…The AMP-activated protein kinase (AMPK) and nuclear factor-E2-related factor-2 (Nrf2) pathways are involved in the regulation of inflammation and redox signaling [ 17 - 19 ]. Moreover, several papers have reported that AMPK contributes to the suppression of proinflammatory reactions via Nrf2 activation [ 20 - 22 ].…”

Section: Resultsmentioning

confidence: 99%

Regulation of neuroinflammation by matrix metalloproteinase-8 inhibitor derivatives in activated microglia and astrocytes

et al. 2017

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Matrix metalloproteinases (MMPs) play a pivotal role in neuroinflammation that is associated with neurodegenerative diseases. Our group recently reported that MMP-8 mediates inflammatory reactions by modulating the processing of TNF-α. To improve the efficacy of the currently available MMP-8 inhibitor (M8I), we have synthesized structurally modified M8I derivatives (comp 2, 3, 4, 5) and compared their efficacy with original compound (comp 1). Among M8I derivatives, comp 2, 3, and 5 inhibited the production of NO, ROS, and IL-6 more efficiently than the original compound in lipopolysaccharide (LPS)-stimulated microglia. When we compared the anti-inflammatory mechanisms of the most effective derivative, comp 3, with comp 1, comp 3 suppressed the mRNA expression of iNOS and cytokines more efficiently than comp 1. Although comp 1 inhibits only TNF-α processing, comp 3 additionally inhibits the expression of TNF-α. Both compounds inhibited LPS-induced activity of MAP kinases, NF-κB, and AP-1, while they increased heme oxygenase-1 expression by upregulating AMPK-Nrf2 signaling. Overall, the effect of comp 3 on anti-inflammatory signaling was much stronger than comp 1. We verified the anti-inflammatory effects of comp 1 and 3 in the LPS-injected mouse brain and primary cultured astrocytes. Comp 1 and 3 suppressed microglial activation, astrogliosis, and proinflammatory gene expression in the brain. Moreover, the compounds inhibited proinflammatory gene expression in the cultured astrocytes. Collectively, our data suggest that the MMP-8 inhibitor may be a promising therapeutic agent for neuroinflammatory disorders.

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Lonchocarpine Increases Nrf2/ARE-Mediated Antioxidant Enzyme Expression by Modulating AMPK and MAPK Signaling in Brain Astrocytes

Cited by 41 publications

References 34 publications

3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes

3-Bromo-4,5-dihydroxybenzaldehyde Enhances the Level of Reduced Glutathione via the Nrf2-Mediated Pathway in Human Keratinocytes

Vorinostat: a histone deacetylases (HDAC) inhibitor ameliorates traumatic brain injury by inducing iNOS/Nrf2/ARE pathway

Regulation of neuroinflammation by matrix metalloproteinase-8 inhibitor derivatives in activated microglia and astrocytes

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