Oxymatrine attenuates cognitive deficits through SIRT1-mediated autophagy in ischemic stroke

J Neuroimmunol. 2018 Oct 15:323:136-142. doi: 10.1016/j.jneuroim.2018.06.018. Epub 2018 Jun 30.

Abstract

To investigate if oxymatrine could ameliorate hippocampus ischemia/reperfusion (I/R) injury induced in rats and explore the possible mechanism. Rats were randomly divided into four groups: sham group, I/R group, I/R + OMT-treated group, I/R + Vehicle-treated group. Oxymatrine or vehicle solution was intraperitoneally injected OMT (150 mg/kg) 60 min before renal ischemia respectively. Water maze was measured; cell apoptosis was assessed by doing TUNEL assay and detecting the expression of P53, Bax, and Cleaved-Caspase-3; autophagy were assessed by measuring the expression of LC3 and P62. The expression of SIRT1 was also detected. Oxymatrine treatment alleviated histological injury in I/R rats, inhibiting apoptosis, promoting autophagy and accompanied by upregulated expression of SIRT1 proteins. Oxymatrine may attenuate hippocampus ischemia/reperfusion injury through upregulation SIRT1, further influencing the processes of apoptosis and autophagy.

Keywords: Bax; Hippocampus; Ischemia/reperfusion; LC3; Oxymatrine; SIRT1; p53.

MeSH terms

  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use*
  • Animals
  • Anti-Arrhythmia Agents / pharmacology
  • Anti-Arrhythmia Agents / therapeutic use
  • Autophagy / drug effects*
  • Autophagy / physiology
  • Brain Ischemia / drug therapy
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Cognitive Dysfunction / drug therapy
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism*
  • Male
  • Quinolizines / pharmacology
  • Quinolizines / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sirtuin 1 / biosynthesis*
  • Sirtuin 1 / genetics
  • Stroke / drug therapy
  • Stroke / genetics
  • Stroke / metabolism*

Substances

  • Alkaloids
  • Anti-Arrhythmia Agents
  • Quinolizines
  • oxymatrine
  • Sirt1 protein, rat
  • Sirtuin 1