Paeoniflorin Alleviates H2O2-Induced Oxidative Injury Through Down-Regulation of MicroRNA-135a in HT-22 Cells

Neurochem Res. 2019 Dec;44(12):2821-2831. doi: 10.1007/s11064-019-02904-3. Epub 2019 Nov 14.

Abstract

Paeoniflorin (PF) has been reported to possess neuroprotective influences on cognitive dysfunction illness. In current research, we attempted to probe into the protective influences of PF against H2O2-induced damage and the underlying regulating mechanisms on hippocampal HT-22 cells. HT-22 cells were pretreated with PF, and then induced by H2O2. Afterwards, the influences of PF pretreatment were examined using CCK-8 assay, apoptosis assay, western blot and ROS assay, respectively. In addition, the expression of microRNA-135a (miR-135a) was analyzed and altered by qRT-PCR and cell transfection, respectively. After overexpression of miR-135a, the effects of miR-135a mimic on cell functions were detected again. Moreover, influences of H2O2, PF and miR-135a overexpression on JAK2/STAT3 and ERK1/2 signal pathways were further investigated. Further experiments verified that PF pretreatment alleviated H2O2-induced oxidative stress through increasing cell viability, inhibiting cell apoptosis, reducing ROS generation and activating JAK2/STAT3 and ERK1/2 pathways. Besides, expression of miR-135a was declined by PF pretreatment. Whereas, miR-135a mimic abrogated the protective effects triggered by PF pretreatment. These results indicated that PF can alleviate H2O2-induced oxidative stress by down-regulation of miR-135a via activation of JAK2/STAT3 and ERK1/2 pathways.

Keywords: Alzheimer disease; Cell apoptosis; ERK1/2 pathways; JAK2/STAT3 pathway; Paeoniflorin; ROS.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Down-Regulation*
  • Glucosides / pharmacology*
  • Hydrogen Peroxide / pharmacology
  • Janus Kinase 2 / metabolism
  • Janus Kinase 3 / metabolism
  • Mice
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Monoterpenes / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Glucosides
  • MicroRNAs
  • Mirn135 microRNA, mouse
  • Monoterpenes
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • peoniflorin
  • Hydrogen Peroxide
  • Jak2 protein, mouse
  • Jak3 protein, mouse
  • Janus Kinase 2
  • Janus Kinase 3
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3