Isoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway
Alzheimer’s disease (AD) is a severe neurodegenerative disorder. AD is pathologically characterized by the formation of intracellular neurofibrillary tangles, and extracellular amyloid plaques which were comprised of amyloid-beta (Aβ) peptides. Aβ induces neurodegeneration by activating microglia, w...
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oai:doaj.org-article:4baf7a9168aa4bf180c7eed07365810e2021-11-25T18:29:30ZIsoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway10.3390/molecules262270561420-3049https://doaj.org/article/4baf7a9168aa4bf180c7eed07365810e2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/7056https://doaj.org/toc/1420-3049Alzheimer’s disease (AD) is a severe neurodegenerative disorder. AD is pathologically characterized by the formation of intracellular neurofibrillary tangles, and extracellular amyloid plaques which were comprised of amyloid-beta (Aβ) peptides. Aβ induces neurodegeneration by activating microglia, which triggers neurotoxicity by releasing various inflammatory mediators and reactive oxygen species (ROS). Nuclear factor-kappa B (NF-κB) is expressed in human tissues including the brain and plays an important role in Aβ-mediated neuronal inflammation. Thus, the identification of molecules that inhibit the NF-κB pathway is considered an attractive strategy for the treatment and prevention of AD. Isoorientin (3′,4′,5,7-Tetrahydroxy-6-C-glucopyranosyl flavone; ISO), which can be extracted from several plant species, such as <i>Philostachys</i> and <i>Patrinia</i> is known to have various pharmacological activities such as anticancer, antioxidant, and antibacterial activity. However, the effect of ISO on Aβ-mediated inflammation and apoptosis in the brain has yet to be elucidated. In the present study, we investigated whether ISO regulated Aβ-induced neuroinflammation in microglial cells and further explored the underlying mechanisms. Our results showed that ISO inhibited the expression of iNOS and COX-2 induced by Aβ<sub>25–35.</sub> And, it inhibited the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, ISO reduced the ROS production in Aβ<sub>25–35</sub>-induced BV2 cells and inhibited NF-κB activation. Furthermore, ISO blocked Aβ<sub>25–35</sub>-induced apoptosis of BV2 cells. Based on these findings, we suggest that ISO represents a promising therapeutic drug candidate for the treatment and prevention of AD.Buyun KimKi Yong LeeByoungduck ParkMDPI AGarticleAlzheimer’s diseaseamyloid-betaROSNF-κBinflammationOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 7056, p 7056 (2021) |
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Alzheimer’s disease amyloid-beta ROS NF-κB inflammation Organic chemistry QD241-441 |
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Alzheimer’s disease amyloid-beta ROS NF-κB inflammation Organic chemistry QD241-441 Buyun Kim Ki Yong Lee Byoungduck Park Isoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway |
description |
Alzheimer’s disease (AD) is a severe neurodegenerative disorder. AD is pathologically characterized by the formation of intracellular neurofibrillary tangles, and extracellular amyloid plaques which were comprised of amyloid-beta (Aβ) peptides. Aβ induces neurodegeneration by activating microglia, which triggers neurotoxicity by releasing various inflammatory mediators and reactive oxygen species (ROS). Nuclear factor-kappa B (NF-κB) is expressed in human tissues including the brain and plays an important role in Aβ-mediated neuronal inflammation. Thus, the identification of molecules that inhibit the NF-κB pathway is considered an attractive strategy for the treatment and prevention of AD. Isoorientin (3′,4′,5,7-Tetrahydroxy-6-C-glucopyranosyl flavone; ISO), which can be extracted from several plant species, such as <i>Philostachys</i> and <i>Patrinia</i> is known to have various pharmacological activities such as anticancer, antioxidant, and antibacterial activity. However, the effect of ISO on Aβ-mediated inflammation and apoptosis in the brain has yet to be elucidated. In the present study, we investigated whether ISO regulated Aβ-induced neuroinflammation in microglial cells and further explored the underlying mechanisms. Our results showed that ISO inhibited the expression of iNOS and COX-2 induced by Aβ<sub>25–35.</sub> And, it inhibited the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, ISO reduced the ROS production in Aβ<sub>25–35</sub>-induced BV2 cells and inhibited NF-κB activation. Furthermore, ISO blocked Aβ<sub>25–35</sub>-induced apoptosis of BV2 cells. Based on these findings, we suggest that ISO represents a promising therapeutic drug candidate for the treatment and prevention of AD. |
format |
article |
author |
Buyun Kim Ki Yong Lee Byoungduck Park |
author_facet |
Buyun Kim Ki Yong Lee Byoungduck Park |
author_sort |
Buyun Kim |
title |
Isoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway |
title_short |
Isoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway |
title_full |
Isoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway |
title_fullStr |
Isoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway |
title_full_unstemmed |
Isoorientin Inhibits Amyloid β<sub>25–35</sub>-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-κB Signaling Pathway |
title_sort |
isoorientin inhibits amyloid β<sub>25–35</sub>-induced neuronal inflammation in bv2 cells by blocking the nf-κb signaling pathway |
publisher |
MDPI AG |
publishDate |
2021 |
url |
https://doaj.org/article/4baf7a9168aa4bf180c7eed07365810e |
work_keys_str_mv |
AT buyunkim isoorientininhibitsamyloidbsub2535subinducedneuronalinflammationinbv2cellsbyblockingthenfkbsignalingpathway AT kiyonglee isoorientininhibitsamyloidbsub2535subinducedneuronalinflammationinbv2cellsbyblockingthenfkbsignalingpathway AT byoungduckpark isoorientininhibitsamyloidbsub2535subinducedneuronalinflammationinbv2cellsbyblockingthenfkbsignalingpathway |
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