The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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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

  • Yang, Fan (Department of Clinical Nutrition, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology) ;
  • Li, Ya (Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University) ;
  • Sheng, Xun (School of Stomatology, Kunming Medical University) ;
  • Liu, Yu (Department of Pharmacy, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology)
  • Received : 2019.12.18
  • Accepted : 2020.04.14
  • Published : 2021.03.01
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Abstract

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.

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References

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