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Life Sci. 2019 May 15. pii: S0024-3205(19)30338-8. doi: 10.1016/j.lfs.2019.04.070. [Epub ahead of print]

Oxymatrine protects neonatal rat against hypoxic-ischemic brain damage via PI3K/Akt/GSK3β pathway.

Author information

1
College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; College of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu Province, 210009, PR China.
2
College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China.
3
College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; College of Pharmacy, the Second Military Medical University, Shanghai, 200433, PR China.
4
College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; Ningxia Hui Medicine Modern Engineering Research Center, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China; Collaborative Innovation Center, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, PR China. Electronic address: YujqLab@163.com.

Abstract

AIMS:

In this study we aimed to explore the specific effect and mechanism of oxymatrine on neonatal rats hypoxic-ischemic brain damage.

MATERIALS AND METHODS:

Hypoxia-ischemia damage model was built by ligaturing the left common carotid artery in 7-day-old rat. Rat pups in OMT group received intraperitoneal injection with oxymatrine (120 mg/kg). Oxygen glucose deprivation/reperfusion model was created in hippocampal neurons. Neurological behavioral, histopathological alteration, cell viability, intracellular Ca2+ concentration, MMP and cell apoptosis were used in damage evaluation.

KEY FINDINGS:

The results shown that oxymatrine regulated brain damage and cell apoptosis by controlling NR2B-PI3K/Akt/GSK3β signaling pathway.

SIGNIFICANCE:

Neonatal hypoxic-ischemic brain damage is a destructive injury that leading to death and detrimental neurological deficits. Oxymatrine is a natural alkaloid compound that can alleviate the ischemic cerebral infarction. In the study, 120 mg/kg oxymatrine decreased neuroethology damage and neuronal damage in the cerebral cortex and the hippocampus CA3. Moreover, 0.2, 1, 5 μg/ml oxymatrine improved cell survival, decreased cell apoptosis. The utilization of LY293004 (PI3K signaling pathway inhibitor) also supported that oxymatrine ameliorated neonatal hypoxic-ischemic brain damage and cell injury by controlling NR2B-PI3K/Akt/GSK3β signaling pathway.

KEYWORDS:

NMDA; Neonatal hypoxic-ischemic; Neuroprotective; Oxymatrine; PI3K pathway

PMID:
31102745
DOI:
10.1016/j.lfs.2019.04.070

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