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Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury
Neonatal hypoxia/ischemia (H/I), injures white matter, results in neuronal loss, disturbs myelin formation, and neural network development. Neuroinflammation and oxidative stress have been reported in neonatal hypoxic brain injuries. We investigated whether Paeoniflorin treatment reduced H/I-induced...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Physiological Society and The Korean Society of Pharmacology
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893490/ https://www.ncbi.nlm.nih.gov/pubmed/33602880 http://dx.doi.org/10.4196/kjpp.2021.25.2.97 |
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author | Yang, Fan Li, Ya Sheng, Xun Liu, Yu |
author_facet | Yang, Fan Li, Ya Sheng, Xun Liu, Yu |
author_sort | Yang, Fan |
collection | PubMed |
description | Neonatal hypoxia/ischemia (H/I), injures white matter, results in neuronal loss, disturbs myelin formation, and neural network development. Neuroinflammation and oxidative stress have been reported in neonatal hypoxic brain injuries. We investigated whether Paeoniflorin treatment reduced H/I-induced inflammation and oxidative stress and improved white matter integrity in a neonatal rodent model. Seven-day old Sprague–Dawley pups were exposed to H/I. Paeoniflorin (6.25, 12.5, or 25 mg/kg body weight) was administered every day via oral gavage from postpartum day 3 (P3) to P14, and an hour before induction of H/I. Pups were sacrificed 24 h (P8) and 72 h (P10) following H/I. Paeoniflorin reduced the apoptosis of neurons and attenuated cerebral infarct volume. Elevated expression of cleaved caspase-3 and Bad were regulated. Paeoniflorin decreased oxidative stress by lowering levels of malondialdehyde and reactive oxygen species generation and while, and it enhanced glutathione content. Microglial activation and the TLR4/NF-κB signaling were significantly down-regulated. The degree of inflammatory mediators (interleukin 1β and tumor necrosis factor-α) were reduced. Paeoniflorin markedly prevented white matter injury via improving expression of myelin binding protein and increasing O1-positive olidgodendrocyte and O4-positive oligodendrocyte counts. The present investigation demonstrates the potent protective efficiency of paeoniflorin supplementation against H/I-induced brain injury by effectually preventing neuronal loss, microglial activation, and white matter injury via reducing oxidative stress and inflammatory pathways. |
format | Online Article Text |
id | pubmed-7893490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Korean Physiological Society and The Korean Society of Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-78934902021-03-01 Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury Yang, Fan Li, Ya Sheng, Xun Liu, Yu Korean J Physiol Pharmacol Original Article Neonatal hypoxia/ischemia (H/I), injures white matter, results in neuronal loss, disturbs myelin formation, and neural network development. Neuroinflammation and oxidative stress have been reported in neonatal hypoxic brain injuries. We investigated whether Paeoniflorin treatment reduced H/I-induced inflammation and oxidative stress and improved white matter integrity in a neonatal rodent model. Seven-day old Sprague–Dawley pups were exposed to H/I. Paeoniflorin (6.25, 12.5, or 25 mg/kg body weight) was administered every day via oral gavage from postpartum day 3 (P3) to P14, and an hour before induction of H/I. Pups were sacrificed 24 h (P8) and 72 h (P10) following H/I. Paeoniflorin reduced the apoptosis of neurons and attenuated cerebral infarct volume. Elevated expression of cleaved caspase-3 and Bad were regulated. Paeoniflorin decreased oxidative stress by lowering levels of malondialdehyde and reactive oxygen species generation and while, and it enhanced glutathione content. Microglial activation and the TLR4/NF-κB signaling were significantly down-regulated. The degree of inflammatory mediators (interleukin 1β and tumor necrosis factor-α) were reduced. Paeoniflorin markedly prevented white matter injury via improving expression of myelin binding protein and increasing O1-positive olidgodendrocyte and O4-positive oligodendrocyte counts. The present investigation demonstrates the potent protective efficiency of paeoniflorin supplementation against H/I-induced brain injury by effectually preventing neuronal loss, microglial activation, and white matter injury via reducing oxidative stress and inflammatory pathways. The Korean Physiological Society and The Korean Society of Pharmacology 2021-03-01 2021-03-01 /pmc/articles/PMC7893490/ /pubmed/33602880 http://dx.doi.org/10.4196/kjpp.2021.25.2.97 Text en Copyright © Korean J Physiol Pharmacol This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Yang, Fan Li, Ya Sheng, Xun Liu, Yu Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury |
title | Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury |
title_full | Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury |
title_fullStr | Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury |
title_full_unstemmed | Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury |
title_short | Paeoniflorin treatment regulates TLR4/NF-κB signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury |
title_sort | paeoniflorin treatment regulates tlr4/nf-κb signaling, reduces cerebral oxidative stress and improves white matter integrity in neonatal hypoxic brain injury |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893490/ https://www.ncbi.nlm.nih.gov/pubmed/33602880 http://dx.doi.org/10.4196/kjpp.2021.25.2.97 |
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